Abstract
The Mongolian gerbil (Meriones unguiculatus) is extremely susceptible to carotid occlusion because of the peculiar anatomical occurrence of an incomplete circle of Willis without posterior communicating artery and a frequently rudimentary anterior communicating artery. Clamping of both carotid arteries induces a bilateral temporary brain ischemia (Levine and Sohn 1969; Bosma et al. 1981; Mršulja et al. 1983; Hossman et al. 1983; Chandler et al. 1985). This pathological animal model allows the simulation of circulatory disturbances in the human brain. The hippocampus is one of the most vulnerable regions of the brain to ischemia and anoxia. The gerbil is known to develop selective neuronal damage in the CA1 sector of the hippocampus following brief periods of forebrain ischemia. This damage differs from conventionally described ischemic neuronal injury because of its slow development (Ito et al. 1975; Kirono 1982; Hossman et al. 1983). The occlusion time can be varied allowing determination of various parameters, e.g., ischemia-induced amnesia.
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References
Cerebral Ischemia by Carotid Artery Occlusion in Mongolian Gerbils
Bosma HJ, Paschen W, Hossman KA (1981) Cerebral ischemia in gerbils using a modified vascular occlusion model. In: Meyer JS, Lechner H, Reivich M, Ott EO, Aranibar A (eds) Cerebral vascular disease 3. Excerpta Medica, Amsterdam, pp 280â285
Chandler MJ, DeLeo J, Carney JM (1985) An unanesthetized-gerbil model of cerebral ischemia-induced behavioral changes. J Pharmacol Meth 14:137â146
Delbarre G, Delbarre B, Barrau Y (1988) A suitable method to select gerbils with incomplete circle of Willis. Stroke 19:126
DeLeo J, Toth L, Schubert P, Rudolphi K, Kreutzberg GW (1987) Ischemia-induced neuronal cell death, calcium accumulation, and glial response in the hippocampus of the Mongolian gerbil and protection by propentofylline (HWA 285). J Cerebr Blood Flow Metab 7:745â751
Dux E, Fastbo J, Ungerstedt U, Rudolphi K, Fredholm BB (1990) Protective effect of adenosine and a novel xanthine derivative propentofylline on the cell damage after bilateral carotid occlusion in the gerbil hippocampus. Brain Res 516:248â256
Fredholm BB, Dunwiddie TV, Bergman B, Lindström K (1984) Levels of adenosine and adenine nucleotides in slices of rat hippocampus. Brain Res 295:127â136
Graeber MB, Kreutzberg GW (1986) Astrocytes increase in glial fibrillary acidic protein during retrograde changes of facial motor neurons. J Neurocytol 15:363â373
Hossman KA, Mies G, Paschen W, Matsuoka Y, Schuier FJ, Bosma HJ (1983) Experimental infarcts in cats, gerbils and rats. In: Stefanovich V (ed) Stroke: animal models. Pergamon Press, Oxford/New York, pp 123â137
Ito M, Spatz M, Walker JT, Klatzo I (1975) Experimental cerebral ischemia in Mongolian gerbils. 1. Light microscopic observations. Acta neuropathol (Berl) 32:209â223
Kashiwa HK, Atkinson WG (1963) The applicability of a new Schiff base glyoxal bis (2-hydroxy-anil), for the cytochemical localization of ionic calcium. J Histochem Cytochem 11:258â264
Kindy MA, Bhat AN, Bhat NR (1992) Transient ischemia stimulates glial fibrillary acid protein and vimentine gene expression in the gerbil neocortex, striatum and hippocampus. Mol Brain Res 13:199â206
Kirono T (1982) Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res 239:57â69
Levine S, Sohn D (1969) Cerebral ischemia in infant and adult gerbils. Arch Pathol 87:315â317
Lundy EF, Solik BS, Frank RS, Lacy PS, Combs DJ, Zelenok GB, DâAlecy LG (1986) Morphometric evaluation of brain infarcts in rats and gerbils. J Pharmacol Meth 16:201â214
McRae A, Rudolphi KA, Schubert P (1994) Propentofylline depresses amyloid and Alzheimerâs CSF antigens after ischemia. Neuro Rep 5:1193â1196
MrÅ¡ulja BB, MicÃc DV, Djuricic BM (1983) Gerbil stroke model: an approach to the study of therapeutic aspects of postischemic brain edema. In: Stefanovich V (ed) Stroke: animal models. Pergamon Press, Oxford/New York, pp 45â62
Nurse S, Corbett D (1996) Neuroprotection after several days of mild, drug-induced hypothermia. J Cerebr Blood Flow Metab 16:474â480
Rudolphi KA, Keil M, Hinze HJ (1987) Effect of theophylline on ischemically induced hippocampal damage in Mongolian gerbils: a behavioral and histopathological study. J Cerebr Blood Flow Metab 7:74â81
Sasaki M, Naritomi H, Kanashiro M, Nishimura H, Sawada T (1989) Effects of propentofylline on energy metabolism of the ischemic brain studied by in vivo 31P nuclear magnetic resonance spectroscopy. Arzneim Forsch/Drug Res 39:886â889
Zetterström T, Vernet L, Ungerstedt U, Tossman U, Jonzon B, Fredholm BB (1982) Purine levels in the intact rat brain. Studies with an implanted hollow fibre. Neurosci Lett 29:111â115
Forebrain Ischemia in Rats
Andjus RK, Suhara K, Sloviter HA (1967) An isolated, perfused rat brain preparation, its spontaneous and stimulated activity. J Appl Physiol 22:1033â1039
Gilboe DD, Cotanch WW, Glover MB (1965) Isolation and mechanical maintenance of the dog brain. Nature 206:94â96
Himori N, Watanabe H, Akaike N, Kurasawa M, Itoh J, Tanaka Y (1990) Cerebral ischemia model with conscious mice. Involvement of NMDA receptor activation and derangement of learning and memory ability. J Pharmacol Meth 23:311â327
Kochhar A, Zivin JA, Lyden PD, Mazzarella V (1988) Glutamate antagonist therapy reduces neurologic deficits produced by focal central nervous system ischemia. Arch Neurol 45:148â153
Krieglstein J, Peruche B (1991) Pharmakologische Grundlagen der Therapie der zerebralen IschÀmie. Arzneim Forsch/Drug Res 31:303â309
Krieglstein G, Krieglstein J, Stock R (1972) Suitability of the isolated perfused rat brain for studying effects on cerebral metabolism. Naunyn-Schmiedebergâs Arch Pharmacol 275:124â134
Nuglisch J, Karkoutly C, Mennel HD, RoÃberg C, Krieglstein J (1990) Protective effect of nimodipine against neuronal damage in rat hippocampus without changing postischemic cerebral blood flow. J Cerebr Blood Flow Metab 10:654â659
Nuglisch J, Rischke R, Krieglstein J (1991) Preischemic administration of flunarizine or phencyclidine reduces local cerebral glucose utilization in rat hippocampus seven days after ischemia. Pharmacology 42:333â339
Oberpichler H, Sauer D, RoÃberg C, Mennel HD, Krieglstein J (1990) PAF antagonist ginkgolide B reduces postischemic neuronal damage in rat brain hippocampus. J Cerebr Blood Flow Metab 10:133â135
Peruche B, Klaassens H, Krieglstein J (1995) Quantitative analysis of the electrocorticogram after forebrain ischemia in the rat. Pharmacology 50:229â237
Pradillo JM, Fernández-López D, GarcÃa-Yébenes I, Sobrado M, Hurtado O, Moro MA, Lizasoain I (2009) Toll-like receptor 4 is involved in neuroprotection afforded by ischemic preconditioning. J Neurochem 109(1):287â294
Prehn JHM, Backhauà C, Karkoutly C, Nuglisch J, Peruche B, RoÃberg C, Krieglstein J (1991) Neuroprotective properties of 5-HT1A receptor agonists in rodent models of focal and global cerebral ischemia. Eur J Pharmacol 203:213â222
Rischke R, Krieglstein J (1990) Effects of Vinpocetin on local cerebral blood flow and glucose utilization seven days after forebrain ischemia in the rat. Pharmacology 41:153â160
Rischke R, Krieglstein J (1991) Postischemic neuronal damage causes astroglial activation and increase in local cerebral glucose utilization in rat hippocampus. J Cerebr Blood Flow Metab 11:106â113
Sakurada O, Kennedy C, Jehle J, Brown JD, Carbin O, Sokoloff L (1978) Measurement of local cerebral blood flow with iodo[14C]-antipyrine. Am J Physiol 234:H59âH66
Seif el Nasr M, Peruche B, RoÃberg C, Mennel HD, Krieglstein J (1990) Neuroprotective effect of memantine demonstrated in vivo and in vitro. Eur J Pharmacol 185:19â24
Seif el Nasr M, Nuglisch J, Krieglstein J (1992) Prevention of ischemia-induced cerebral hypothermia by controlling the environmental temperature. J Pharmacol Meth 27:23â26
Smith ML, Auer RN, Siesjö BK (1984a) The density and distribution of ischemic brain injury in the rat following 2â10 min of forebrain ischemia. Acta Neuropathol (Berl) 64:319â332
Smith ML, Bendek G, Dahlgren N, Rosén I, Wieloch T, Siesjö BK (1984b) Models for studying long-term recovery following forebrain ischemia in the rat. 2. A 2-vessel occlusion model. Acta Neurol Scand 69:385â401
Sokoloff L, Reivich M, Kennedy C, DesRosiers MH, Patlak CS, Pettigrew KD, Sakurada O, Shinohara M (1977) The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem 28:897â916
Hypoxia Tolerance Test in Rats
Hossman KA, Mies G, Paschen W, Matsuoka Y, Schuier FJ, Bosma HJ (1983) Experimental infarcts in cats, gerbils and rats. In: Stefanovich V (ed) Stroke: animal models. Pergamon Press, Oxford/New York, pp 123â137
Middle Cerebral Artery Occlusion in Rats
Backhauà C, Karkoutly C, Welsch M, Krieglstein J (1992) A mouse model of focal cerebral ischemia for screening neuroprotective drug effects. J Pharmacol Meth 27:27â32
Bederson JB, Pitts LH, Tsuji M, Nishimura MC, Davis RL, Bartkowski H (1986a) Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination. Stroke 17:472â476
Bederson JB, Pitts LH, Germano SM, Nishimura MC, Davis RL, Bartkowski HM (1986b) Evaluation of 2,3,5-triphenyltetrazolium chloride as a stain for detection and quantification of experimental cerebral infarction in rats. Stroke 17:1304â1308
Christoforidis GA, Rink C, Kontzialis MS, Mohammad Y, Koch RM, Abduljalil AM, Bergdall VK, Roy S, Khanna S, Slivka AP, Knopp MV, Sen CK (2011) An endovascular canine middle cerebral artery occlusion model for the study of leptomeningeal collateral recruitment. Invest Radiol 46(1):34â40
De Ley G, Weyne J, Demeester G, Stryckman K, Goethals P, Van de Velde E, Leusen I (1988) Experimental thromboembolic stroke studied by positron emission tomography: immediate versus delayed reperfusion by fibrinolysis. J Cerebr Blood Flow Metab 8:539â545
Du C, Hu R, Csernansky CA, Liu XZ, Hsu CY, Choi DW (1996) Additive neuroprotective effects of dextrorphan and cycloheximide in rats subjected to transient focal cerebral ischemia. Brain Res 718:233â236
Engel O, Kolodziej S, Dirnagl U, Prinz V (2011) Modeling stroke in mice â middle cerebral artery occlusion with the filament model. J Vis Exp 47:2423
Germano IM, Pitts LH, Meldrum BS, Bartkowski HM, Simon RP (1987) Kynurenate inhibition of cell excitation decreases stroke size and deficits. Ann Neurol 22:730â734
Ginsberg MD, Busto R (1989) Rodent models of cerebral ischemia. Stroke 20:1627â1642
Gotti B, Duverger G, Bertin J, Carter C, Dupont R, Frost J, Gaudilliere B, MacKenzie ET, Rousseau J, Scatton B, Wick A (1988) Ifenprodil and SL 82.0715 as cerebral antiischemic agents. I. Evidence for efficacy in models of focal cerebral ischemia. J Pharm Exp Ther 247:1211â1221
Hara H, Huang PL, Panahian N, Fishman MC, Moskowitz MA (1996) Reduced brain edema and infarction volume in mice lacking the neuronal isoform of nitric oxide synthase after transient MCA occlusion. J Cerebr Blood Flow Metab 16:605â611
Hara H, Friedlander RM, Gagliardini V, Ayata C, Fink K, Huang Z, Shimizu-Sasamata M, Yuan J, Moskowitz MA (1997) Inhibition of interleukin 1β converting enzyme family proteases reduces ischemic and excitotoxic neuronal damage. Proc Natl Acad Sci U S A 94:2007â2012
Hossmann KA (1982) Treatment of experimental cerebral ischemia. J Cerebr Blood Flow Metab 2:275â297
Hossmann KA, Schuier FJ (1980) Experimental brain infarcts in cats. I Pathophysiological observations. Stroke 11:583â592
Huang PL, Dawson PM, Bredt DS, Snyder SH, Fishman MC (1994) Targeted disruption of the neuronal nitric oxide synthase gene. Cell 75:1273â1286
Nsihimura A, Hamada T, Fukuzaki K, Miyajima H, Nagata R, Kito G (1998) A new model of experimental thromboembolic stroke in cynomolgus monkey. Naunyn-Schmiedebergâs Arch Pharmacol 358(Suppl 1):R70
Park CK, Rudolphi KA (1994) Antiischemic effects of propentofylline (HWA 285) against focal cerebral infarction in rats. Neurosci Lett 178:235â238
Park CK, McCulloch J, Kang JK, Choi CR (1992) Efficacy of DCPPene, a competitive N-methyl-d-aspartate antagonist in focal cerebral ischemia in the rat. Neurosci Lett 147:41â44
Salom JB, Barberá MD, Centeno JM, Ortà M, Torregrosa G, Alborch E (1999) Relaxant effects of sodium nitroprusside and NONOates in goat middle cerebral artery: delayed impairment by global ischemia-reperfusion. Nitric Oxide 3:85â93
Shigeno T, Teasdale GM, McCulloch J, Graham DI (1985) Recirculation model following MCA occlusion in rats. Cerebral blood flow, cerebrovascular permeability, and brain edema. J Neurosurg 63:272â277
Shimamura N, Matsuda N, Katayama K, Ohkuma H (2009) Novel rat middle cerebral artery occlusion model: trans-femoral artery approach combined with preservation of the external carotid artery. J Neurosci Methods 184(2):195â198
Smith SE, Meldrum BS (1992) Cerebroprotective effect of a non-N-methyl-d-aspartate antagonist, GYKI 52466, after focal ischemia in the rat. Stroke 23:861â864
Sundt TM, Waltz AG (1966) Experimental cerebral infarction: retro-orbital, extradural approach for occluding the middle cerebral artery. Mayo Clin Proc 41:159â168
Tamura A, Graham DI, McCulloch J, Teasdale GM (1981) Focal cerebral ischaemia in the rat: 1. Description of technique and early neuropathological consequences following middle cerebral artery occlusion. J Cerebr Blood Flow Metab 1:53â60
Van Winkle JA, Chen B, Lei IF, Pereira B, Rajput PS, Lyden PD (2013) Concurrent middle cerebral artery occlusion and intra-arterial drug infusion via ipsilateral common carotid artery catheter in the rat. J Neurosci Methods 213(1):63â69
Welsh FA, Sakamoto T, McKee AE, Sims RE (1987) Effect of lactacidosis on pyridine nucleotide stability during ischemia in mouse brain. J Neurochem 49:846â851
Wu YP, McRae A, Rudolphi K, Ling EA (1999) Propentofylline attenuates microglial reaction in the rat spinal cord induced by middle cerebral artery occlusion. Neurosci Lett 280:17â20
Yamamoto S, Golanov EV, Berger SB, Reis DJ (1992) Inhibition of nitric oxide synthesis increases focal ischemic infarction in rat. J Cerebr Blood Flow Metab 12:717â726
Yang GY, Chen SF, Kinouchi H, Chan PH, Weinstein PR (1992) Edema, cation content and ATPase activity after middle cerebral artery occlusion in rats. Stroke 23:1331â1336
Zu QQ, Liu S, Xu XQ, Lu SS, Sun L, Shi HB (2013) An endovascular canine stroke model: middle cerebral artery occlusion with autologous clots followed by ipsilateral internal carotid artery blockade. Lab Invest 93(7):760â767
Photochemically Induced Focal Cerebral Ischemia in Rats
Boquillon M, Boquillon JP, Bralet J (1992) Photochemically induced, graded cerebral infarction in the mouse by laser irradiation. Evolution of brain edema. J Pharm Meth 27:1â6
Grome JJ, Gojowczyk G, Hofmann W (1990) Effect of chronic intravenous administration of propentofylline (HWA 285) on the volume of focal ischemic damage in the rat. Stroke 21(Suppl I):I-134âI-135, PS-12â11
Kim HS, Kim D, Kim RG, Kim JM, Chung E, Neto PR, Lee MC, Kim HI (2014) A rat model of photothrombotic capsular infarct with a marked motor deficit: a behavioral, histologic, and microPET study. J Cereb Blood Flow Metab 34(4):683â689
Matsuno H, Uematsu T, Umemura K, Tagiguchi Y, Asai Y, Murakana Y, Nakashima M (1993) A simple and reproducible cerebral thrombosis model in rats induced by a photochemical reaction and the effect of a plasmin-plasminogen activator chimera in this model. J Pharm Toxicol Meth 29:165â173
Stieg PE, Sathi S, Warach S, Le DA, Lipton SA (1999) Neuroprotection by the NMDA receptor-associated open-channel blocker memantine in a photothrombotic model of cerebral focal ischemia in neonatal rat. Eur J Pharmacol 375:115â120
Microdialysis and Neuroprotection Experiments After Global Ischemia in Rats
Benveniste H, Drejer J, Schousboe A, Diemer NH (1984) Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis. J Neurochem 43:1369â1374
Block F, Schmitt W, Schwarz M (1996) Pretreatment but not post-treatment with GYKI 52466 reduces functional deficits and neuronal damage after global ischemia in rats. J Neurol Sci 139:167â172
Choi DW (1990) Methods for antagonizing glutamate neurotoxicity. Cerebrovasc Brain Metab 2:105â147
Hagberg H, Andersson P, Lacarewicz J, Jacobson I, Butcher S, Sandberg M (1987) Extracellular adenosine, inosine, hypoxanthine, and xanthine in relation to tissue nucleotides and purines in rat striatum during transient ischemia. J Neurochem 49:227â231
Hagberg H, Andiné P, Fredholm B, Rudolphi K (1990) Effect of the adenosine uptake inhibitor propentofylline on the extracellular adenosine and glutamate and evaluation of its neuroprotective efficacy after ischemia in neonatal and adult rats. In: Krieglstein J, Oberpichler (eds) Pharmacology of cerebral ischemia. Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart, pp 427â437
Lindroth P, Hamberger A, Sandberg M (1985) Liquid chromatographic determination of amino acids after precolumn fluorescence derivatization. In: Boulton AA, Baker GB, Wood JD (eds) Neuromethods. Amino acids, vol 3. HUMANA Press, pp 97â116 http://link.springer.com/protocol/10.1385%2F0-89603-077-6%3A97
Pulsinelli WA, Brierley JB (1979) A new model of bilateral hemispheric ischemia in the unanesthetized rat. Stroke 10:267â272
Sandberg M, Butcher SP, Hagberg H (1986) Extracellular overflow of neuroactive amino acids during severe insulin-induced hypoglycemia: in vivo dialysis of the rat hippocampus. J Neurochem 47:178â184
Hypoxia/Hypoglycemia in Hippocampal Slices
Dunwiddie TV (1986) The use of in vitro brain slices in neuropharmacology. In: Electrophysiological techniques in pharmacology. Alan R. Liss, pp 65â90
Hagberg H, Andiné P, Fredholm B, Rudolphi K (1990) Effect of the adenosine uptake inhibitor propentofylline on the extracellular adenosine and glutamate and evaluation of its neuroprotective efficacy after ischemia in neonatal and adult rats. In: Krieglstein J, Oberpichler (eds) Pharmacology of cerebral ischemia. Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart, pp 427â437
Measurement of Local Cerebral Blood Flow and Glucose Utilization in Rats
Bouwens A, Bolmont T, Szlag D, Berclaz C, Lasser T (2014) Quantitative cerebral blood flow imaging with extended-focus optical coherence microscopy. Opt Lett 39(1):37â40
Choi SR, Magata Y, Saji H, Tajima K, Kitano H, Konishi J, Yokoyama A (1997) Effect of ginseng pretreatment on cerebral glucose metabolism in ischemic rats using animal positron emission tomography (PET) and ([18F]-FDG). Phytother Res 11:437â440
De la Sayette T, Chavoix C, Brouillet A, Hantraye P, Kunimoto M, Khalili-Varasteh M, Guibert B, Prenant C, MaziÚre M (1991) In vivo benzodiazepine receptor occupancy by CL 218,872 visualized by positron emission tomography in the brain of the living baboon: modulation by GABAergic transmission and relation with anticonvulsant activity. Exp Brain Res 83:397â402
Grome J, Stefanovich V (1985) Differential effects of xanthine derivatives on local cerebral blood flow and glucose utilization in the conscious rat. In: Stefanovich V, Rudolphi K, Schubert P (eds) Adenosine: receptors and modulation of cell function. IRL Press, Oxford, pp 453â458
Hawkins RA, Choi Y, Scates S, Rege S, Hoh CK, Glaspy J, Phelps ME (1993) An animal model for in vivo evaluation of tumor glycolytic rates with positron emission tomography. J Surg Oncol 53:104â109
Hume SP, Brown DJ, Ashwoth S, Hirani E, Luthra SK, Lammertsma AA (1997) In vivo saturation kinetics of two dopamine transporter probes measured using a small animal positron emission tomography scanner. J Neurosci Meth 76:45â51
Ito K, Sawada Y, Ishizuka H, Sugiyama Y, Suzuki H, Iga T, Hanano M (1990) Measurement of cerebral glucose utilization from brain uptake of [14C]2-deoxyglucose and [3H]3-O-methylglucose in the mouse. J Pharmacol Meth 23:129â140
Jones HA, Rhodes CR, Law MP, Becket JM, Clark JC, Boobis AR, Taylor GW (1991) Rapid analysis of 11C-labelled drugs: fate of [11C]-S-4-(tert.-butylamino-2-hydroxypropoxy)-benzimidazol-2-one in the dog. J Chromatogr Biomed Appl 570:361â370
Ku T, Choi C (2012) Noninvasive optical measurement of cerebral blood flow in mice using molecular dynamics analysis of indocyanine green. PLoS One 7(10):e48383
Kung HF (1993) SPECT and PET ligands for CNS imaging. Neurotransmissions 9(4):1â6
Lacombe B, Meric P, Seylaz J (1980) Validity of cerebral blood flow measurements obtained with quantitative tracer techniques. Brain Res Rev 2:105â169
Magata Y, Saji H, Choi SR, Tajima K, Takagaki T, Sasayama S, Yonekura Y, Kitano H, Watanabe M, Okada H, Yoshikawa E, Yamashita T, Yokoyama A, Konishi J (1995) Noninvasive measurement of cerebral blood flow and glucose metabolic rate in the rat with high-resolution animal positron emission tomography (PET): a novel in vivo approach for assessing drug action in the brains of small animals. Biol Pharm Bull 18:753â756
McCulloch J, Kelly PAT, Ford I (1982) Effect of apomorphine on the relationship between local cerebral glucose utilization and local cerebral blood flow (with an appendix on its statistical analysis). J Cerebr Blood FlowMetab 2:487â499
Rogers GA, Stone-Elander S, Ingvar M, Eriksson L, Parsons SM, Widen L (1994) 18F-labelled vesamicol derivates: syntheses and preliminary in vivo small animal positron emission tomography evaluation. Nucl Med Biol 21:219â230
Sakurada O, Kennedy C, Jehle J, Brown JD, Carbin O, Sokoloff L (1978) Measurement of local cerebral blood flow with iodo(14C)-antipyrine. Am J Physiol 234:H59âH66
Smith CB (1981) Age-related changes in local rates of cerebral glucose utilization in the rat. In: Enna SJ et al (eds) Brain neurotransmitters and receptors in aging and age-related disorders. Aging, vol 17. Raven Press, New York, pp 195â201
Sokoloff L, Reivich M, Kennedy C, DesRosiers MH, Patlak CS, Pettigrew KD, Sakurada O, Shinohara M (1977) The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem 28:897â916
Winn HR, Rubio GR, Berne RM (1981) The role of adenosine in the regulation of cerebral blood flow. J Cerebr Blood Flow Metab 1:239â244
Wolfson LI, Sakurada O, Sokoloff L (1977) Effects of γ -butyrolactone on local cerebral glucose utilization in the rat. J Neurochem 29:777â783
Cerebrovascular Resistance in Anesthetized Baboons
Clozel M, Watanabe H (1993) BQ-123, a peptidic endothelin ETA receptor antagonist, prevents the early cerebral vasospasm following subarachnoid hemorrhage after intracisternal but not after intravenous injection. Life Sci 52:825â834
Grome JJ, Rudolphi K, Harper AM (1985) Cerebrovascular effects of a xanthine derivative propentofylline (HWA 285). Drug Dev Res 5:111â121
HÞedt-Rasmussen K, Sveinsdottir E, Lassen NA (1966) Regional cerebral blood flow in man determined by intraarterial injection of radioactive inert gas. Circ Res 18:237
Hughes S, Brain S, Williams G, Williams T (1994) Assessment of blood flow changes at multiple sites in rabbit skin using a 133xenon clearance technique. J Pharmacol Toxicol Meth 32:41â47
Imaizumi S, Shimizu H, Ahmad I, Kaminuma T, Tajima M, Yoshimoto T, Megyesi J, Findlay JM, Kikuchi H, Nozaki K (1996) Effect of calcitonin gene-related peptide on delayed vasospasm after experimental subarachnoid hemorrhage in rabbits. Surg Neurol 46:263â271
Inoue T, Shimizu H, Kaminuma T, Tajima M, Watabe K, Yoshimoto T, Dacey RG Jr, Solomon RA, Selman WR (1996) Prevention of cerebral vasospasm by calcitonin gene-related peptide slow-release tablet after subarachnoidal hemorrhage in monkeys. Neurosurgery 39:984â990
Kozniewska E, Oseka M, Stys T (1992) Effects of endothelium derived nitric oxide on cerebral circulation during normoxia and hypoxia in the rat. J Cerebr Blood Flow Metab 12:311â317
Lacombe P, Meric P, Seylaz J (1980) Validity of cerebral blood flow measurements obtained with quantitative tracer techniques. Brain Res Rev 2:105â169
Lin CL, Calisaneller T, Utica N, Dumont AS, Kassell NF, Lee KS (2003) A murine model of subarachnoid hemorrhage-induced cerebral vasospasm. J Neurosci Meth 123:89â97
Nielsen SL, Lassen NA, Elmqvist D (1975) Muscle blood flow in man studied with the local radioisotope method. In: Kunze K, Desmedt JE (eds) Studies on neuromuscular diseases. Proceedings of the international symposium, Giessen 1973, Karger, Basel, pp 79â81
Solomon RA, Antunes JL, Chen RYZ, Bland L, Chien S (1985) Decrease in cerebral blood flow in rats after experimental subarachnoid hemorrhage: a new animal model. Stroke 16:58â64
Varsos VG, Liszczak TM, Han DH, Kistler JP, Vielma J, Black PM, Heros RC, Zervas NT (1983) Delayed cerebral vasospasm is not reversible by aminophylline, nifedipine, or papaverine in a âtwo-hemorrhageâ canine model. J Neurosurg 58:11â17
Veall N, Mallett BL (1966) Regional cerebral blood flow determination by 133Xe inhalation and external recording: the effect of arterial recirculation. Clin Sci 30:353
Wang Q, Paulson OB, Lassen NA (1992) Effect of nitric oxide blockade by N G-nitro-l-arginine on cerebral blood flow response to changes in carbon dioxide tension. J Cerebr Blood Flow Metab 12:947â953
Effect on Cerebral Blood Flow in Cats (Fluvography)
Betz E (1965) Local heat clearance from the brain as a measure of blood flow in acute and chronic experiments. Acta Neurol Scand Suppl 14:29â37
Golenhofen K, Hensel H, Hildebrandt G (1963) Durchblutungsmessungen mit Waerme-Elementen. Georg Thieme Verlag, Stuttgart
Lacombe P, Meric P, Seylaz J (1980c) Validity of cerebral blood flow measurements obtained with quantitative tracer techniques. Brain Res Rev 2:105â169
Effect on Cerebral Blood Flow and in Ischemic Skeletal Muscle in Rats (Laser-Doppler-Effect)
Benessiano J, Levy BI, Michel JB (1985) Instantaneous aortic blood flow measurement with range-gated Doppler flowmeter in anesthetized rat. J Pharmacol Meth 14:99â110
Iadecola C (1992) Does nitric oxide mediate the increases in cerebral blood flow elicited by hypercapnia? Proc Natl Acad Sci U S A 89:3913â3916
Kunze K, Berk H (1975) Oxygen supply and muscle blood flow in normal and diseased muscle. In: Kunze K, Desmedt JE (eds) Studies on neuromuscular diseases. Proceedings of the international symposium, Giessen 1973, Karger, Basel, pp 82â91
LeNoble JLML, Struyker-Boudier HAJ, Smits JFM (1987) Differential effects of general anesthetics on regional vasoconstrictor responses in the rat. Arch Int Pharmacodyn 289:82â92
Partridge BL (1991) The effects of local anesthetics and epinephrine on rat sciatic nerve blood flow. Anesthesiology 75:243â251
Prado R, Watson BD, Kuluz J, Dietrich WD (1992) Endothelium-derived nitric oxide synthase inhibition. Effects on cerebral blood flow, pial artery diameter, and vascular morphology in rats. Stroke 23:1118â1124
Raszkiewicz JL, Linville DG, Kerwin JF, Wagenaar F, Arneric SP (1992) Nitric oxide synthase is critical in mediating basal forebrain regulation of cortical cerebral circulation. J Neurosci Res 33:129â135
Rudquist I, Smith QR, Michel ME, Ask P, Ãberg P, Rapoport SI (1985) Sciatic nerve blood flow measured by laser Doppler flowmetry and [14C]iodoantipyrine. Am J Physiol 248:H311âH317
Traumatic Brain Injury
Basso DM, Beattie MS, Bresnahan JC (1996) Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device versus transection. Exp Neurol 139:244â256
Bemana I, Nagao S (1998) Effects of Niravoline (RU 51599), a selective kappa-opioid receptor agonist on intracranial pressure in gradually expanding extradural mass lesion. J Neurotrauma 15:117â124
Denny-Brown D, Russell WR (1941) Experimental cerebral percussion. Brain 64:93â164
Dixon CE, Clifton GL, Lighthall JW, Yagjmai AA, Haynes RL (1991) A controlled cortical impact model of traumatic brain injury in the rat. J Neurosci Meth 39:253â262
Faddis B, Vijayan VK (1988) Application of glial fibrillary acidic protein histochemistry in the quantification of astrocytes in the rat brain. Am J Anat 183:316â322
Faden AI (1993) Comparison of single and combination drug treatment strategies in experimental brain trauma. J Neurotrauma 10:91â100
Faden AI, Demediuk P, Panter SS, Vink R (1989) The role of excitatory amino acids and NMDA receptors in traumatic brain injury. Science 244:798â800
Fox GB, Fan L, Lavasseur RA, Faden AI (1998) Sustained sensory/motor and cognitive deficits with neuronal apoptosis following controlled impact brain injury in the mouse. J Neurotrauma 15:599â614
Gruner JA (1992) A monitored contusion model of spinal cord injury in the rat. J Neurotrauma 9:123â128
Gurdjian ES, Lissner HR, Webster JE (1954) Studies on experimental concussion. Relation of physiological effect to time duration of intracranial pressure increase at impact. Neurology 4:674â681
Hall ED, Yonkers PA, McCall JM (1988) Effects of the 21-amino-steroid U74006F on experimental head injury in mice. J Neurosurg 68:456â461
Hayes RL, Lewelt W, Yeatts ML (1983) Metabolic, behavioral and electrophysiological correlates of experimental brain injury in the cat. J Cerebr Blood Flow Metab 3:38â40
Hayes RL, Pechura CM, Katayama Y, Povlishock JT, Giebel ML, Becker DP (1984) Activation of pontine cholinergic sites implicated in unconsciousness following cerebral percussion in cats. Science 223:301â303
Kooijman E, Nijboer CH, van Velthoven CT, Kavelaars A, Kesecioglu J, Heijnen CJ (2014) The rodent endovascular puncture model of subarachnoid hemorrhage: mechanisms of brain damage and therapeutic strategies. J Neuroinflammation 11:2
Laurer HL, Lenzlinger PM, McIntosh TK (2000) Models of traumatic brain injury. Eur J Trauma 26:95â100
Lindgren S, Rinder L (1969) Production and distribution of intracranial and intraspinal pressure changes at sudden extradural fluid volume input in rabbits. Acta Physiol Scand 76:340â351
Maegele M, Gruener-Lippert M, Ester-Bode T, Garbe J, Bouillon B, Neugebauer E, Klug N, Lefering R, Neiss WF, Angelov DN (2005) Multimodal early onset stimulation combined with enriched environment is associated with reduced CNS lesion volume and enhanced reversal of neuromotor dysfunction after traumatic brain injury in rats. Eur J Neurosci 21:2406â2418
Marmarou A, Foda MAAE, van den Brink W, Campell J, Kita H, Demetriadu K (1994) A new model of diffuse brain injury in rats. J Neurosurg 80:291â300
McIntosh TK, Vink R, Noble L, Yamakami I, Fernyak S, Soares H, Faden AL (1989) Traumatic brain injury in the rat: characterization of a lateral fluid-percussion model. Neurosci 28:233â244
McIntosh TK, Vink R, Soares H, Hayes R, Simon R (1990) Effect of noncompetitive blockade of N-methyl-d-aspartate receptors on the neurochemical sequelae of experimental brain injury. J Neurochem 55:1170â1179
Mésenge C, Verrecchia C, Allix M, Boulu RR, Plotkine M (1996) Reduction of the neurological deficit in mice with traumatic brain injury by nitric oxide synthase inhibitors. J Neurotrauma 13:209â214
Morganti-Kossmann MC, Yan E, Bye N (2010) Animal models of traumatic brain injury: is there an optimal model to reproduce human brain injury in the laboratory? Injury 41(Suppl 1):S10âS13
Nilsson B, Ponten U, Voigt G (1977) Experimental head injury in the rat. Part 1. Mechanics, pathophysiology, and morphology in an impact acceleration trauma model. J Neurosurg 47(2):241â251
Ommaya AK, Gennarelli TA (1974) Cerebral concussion and traumatic unconsciousness. Correlation of experimental and clinical observations on blunt head injuries. Brain 97:633â654
Petty MA, Poulet P, Haas A, Namer IJ, Wagner J (1996) Reduction of traumatic brain injury-induced cerebral oedema by a free radical scavenger. Eur J Pharmacol 307:149â155
Shohami E, Novikov M, Bass R (1995) Long-term effect of HU211, a novel non-competitive NMDA antagonist, on motor and memory functions after closed head injury in the rat. Brain Res 674:55â62
Springer JE, Azbill RD, Mark RJ, Begley JG, Waeg G, Mattson MP (1997) 4-Hydroxynonenal, a lipid peroxidation product, rapidly accumulates following traumatic spinal cord injury and inhibits glutamate uptake. J Neurochem 68:2469â2476
Sullivan HG, Martinez J, Becker DP, Miller JD, Griffith R, Wist AO (1976) Fluid-percussion model of mechanical brain injury in the cat. J Neurosurg 45:520â534
Sun FY, Faden AI (1995) Neuroprotective effects of 619C89, a use-dependent sodium channel blocker, in rat traumatic brain injury. Brain Res 673:133â140
Tang Y-P, Noda Y, Hasegawa T, Nabeshima T (1997) A concussive-like brain injury model in mice: impairment in learning and memory. J Neurotrauma 14:851â862
Cerebral Blood Flow Measured by MRI
Banfi C, Sironi L, de Simoni G, Gelosa P, Barcella S, Perego C, Gianazza E, Guetrini U, Tremoli E, Mussoni L (2004) Pentoxifylline prevents spontaneous brain ischemia in stroke-prone rats. J Pharmacol Exp Ther 310:890â895
Beckmann N, Tigani B, Mazzoni L, Fozzard JR (2003) Techniques: magnetic resonance imaging of the lung provides potential for non-invasive preclinical evaluation of drugs. Trends Pharmacol Sci 24:550â554
Beckmann N, Laurent D, Tigani B, Panizzutti R, Rudin M (2004) Magnetic resonance imaging in drug discovery: lessons from disease areas. Drug Dis Today 9:35â42
Belayev L, Alonso OF, Busto R, Zhao W, Ginsberg MD (1996) Middle cerebral artery occlusion in the rat by intraluminal suture: neurological and pathological evaluation of an improved model. Stroke 27:1616â1623
Cash D, Beech JS, Rayne RC, Bath PMW, Meldrum BS, Williams SCR (2001) Neuroprotective effect of aminoguanidine on transient focal ischaemia in the rat brain. Brain Res 905:91â103
Cherry SR, Phelps ME (1996) Imaging brain function with positron emission tomography. In: Toga AW, Mazziotta JC (eds) Brain mapping: the methods. Academic, New York, pp 191â221
Elger B, Seega J, Raschack M (1994a) Oedema reduction by levemopamil in focal cerebral ischaemia of spontaneously hypertensive rats studied by magnetic resonance imaging. Eur J Pharmacol 254:65â71
Elger B, Seega J, Brendel R (1994b) Magnetic resonance imaging study on the effect of levemopamil on the size of intracerebral hemorrhage in rats. Stroke 25:1836â1841
Franke C, van Dorsten FA, Olah L, Schwindt W, Hoehn M (2000) Arterial spin tagging perfusion imaging of rat brain: dependency on magnetic field strength. Magn Reson Imaging 18:1109â1113
Henderson LA, Macey PM, Richard CA, Runquist ML, Harper RM (2004) Functional magnetic resonance imaging during hypotension in the developing animal. J Appl Physiol 97:2248â2257
Hoehn-Berlage M, Norris DG, Kohno K, Mies G, Leibfritz D, Hossmann KA (1995) Evolution of regional changes in apparent diffusion coefficient during focal ischemia of rat brain: the relationship of quantitative diffusion NMR imaging to reduction of cerebral blood flow and metabolic disturbances. J Cereb Blood Flow Metab 15:1002â1011
Kerskens CM, Hoehn-Berlage M, Schmitz B, Busch E, Bock C, Gyngell ML, Hossmann KA (1996) Ultrafast perfusion weighted MRI of functional brain activation in rats during forepaw stimulation: comparison with T2*-weighted MRI. NMR Biomed 8:20â23
Le Bihan D, Breton E, Lallemand D, Grenier P, Cabanis E, Laval-Jeantet M (1986) MR imaging of intravoxel incoherent motions: application to diffusion and perfusion in neurologic disorders. Radiology 161:401â407
Leslie RA, James MF (2000) Pharmacological magnetic resonance imaging: a new application for functional MRI. Trends Pharmacol Sci 21:314â318
Ohlstein EH, Romanic AM, Clark LV, Kapadia RD, Sarkar SK, Gagnon R, Chandra S (2000) Application of in vivo and ex vivo magnetic resonance imaging for the evaluation of tranilast on neointima formation following balloon angioplasty of the rat coronary artery. Cardiovasc Res 47:759â768
Paczynski RP, Venkatesan R, Diringer MN, He YY, Hsu CY, Lin W (2000) Effects of fluid management on edema volume and midline shift in a rat model of ischemic stroke. Stroke 31:1702â1708
Petty MA, Neumann-Haefelin C, Kalisch J, Sarhan S, Wettstein JG, Juretschke HP (2003) In vivo neuroprotective effects of ACEA 1021 confirmed by magnetic resonance imaging in ischemic stroke. Eur J Pharmacol 474:53â62
Pevsner PH, Eichenbaum JW, Miller DC, Pivawer G, Eichenbaum KD, Stern A, Zakian KL, Koutcher JA (2001) A photothrombotic model of small early ischemic infarcts in the rat brain with histologic and MRI correlation. J Pharm Toxicol Meth 45:227â233
Reese T, Bjelke B, Porszacz R, Baumann D, Bochelen D, Sauter A, Rudin M (2000) Regional brain activation by bicuculline visualized by functional magnetic resonance imaging. Time-resolved assessment of bicuculline-induced changes in local cerebral blood volume using an intravascular contrast agent. NMR Biomed 13:43â49
Seega J, Elger B (1993) Diffusion- and T 2-weighted imaging: evaluation of oedema reduction in focal cerebral ischaemia by the calcium and serotonin antagonist levemopamil. Magnet Reson Imag 11:401â409
Shirhan MD, Moochala SM, Ng PY, Lu J, Ng KC, Teo L, Yap E, Ng I, Hwang P, Lim T, Sitoh YY, Rumpel H, Jose R, Ling E (2004) Spermine reduces infarction and neurological deficit following a rat model of middle cerebral artery occlusion: a magnetic resonance imaging study. Neuroscience 124:299â304
Swain RA, Harris AB, Wiener EC, Dutka MV, Morris HD, Theien BE, Konda S, Engberg K, Lauterbur PC, Greenough WT (2003) Prolonged exercise induces angiogenesis and increases cerebral blood flow in primary motor cortex of the rat. Neuroscience 117:1037â1046
Zea Longa E, Weinstein PR, Carlson S, Cummins RW (1989) Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 20:84â91
Perfused Hindquarter Preparation with Sympathetic Nerve Stimulation in Rats
Bhattacharya BK, Dadkar NK, Dohadwalla AN (1977) Vascular reactivity of perfused vascular bed in spontaneously hypertensive and normotensive rats. Br J Pharmacol 59:243â246
Bomzon A, Naidu SG (1985) Perfusion of the isolated rat hind limb. An analysis of the technique. J Pharmacol Meth 14:285â296
Brody MJ, Shaffer RA, Dixon RL (1963) A method for the study of peripheral vascular responses in the rat. J Appl Physiol 18:645â647
Champion HC, Duperier CD, Fitzgerald WE, Lambert DG, Murphy WA, Coy DH, Kadowitz PJ (1996) [Mpr14]-rADM(14â50), a novel analog of adrenomedullin, possesses potent vasodilator activity in the hindlimb vascular bed of the cat. Life Sci 59:PL1âPL7
Champion HC, Akers DL, Santiago JA, Lambert DG, McNamara DB, Kadowitz PJ (1997) Analysis of the responses to human synthetic adrenomedullin and calcitonin gene-related peptides in the hindlimb vascular bed of the cat. Mol Cell Biochem 176:5â11
Dadkar NK, Dohadwalla AN, Bhattacharya BK (1977) The effect of tyramine on peripheral vasculature of the spontaneously hypertensive rat. J Pharm Pharmacol 29:48â49
Folkow B, HallbÀck M, Lundgren Y, Weiss L (1970) Background of increased flow resistance and vascular reactivity in spontaneously hypertensive rats. Acta Physiol Scand 80:93â106
Kitzen JM, Long JP, Cannon JG (1978) Pharmacology of 6,7-dihydroxy-2-dimethylaminotetralin (TL-99). I Cardiovascular activity in the dog and cat. J Pharm Exp Ther 206:239â247
Reitan JA, Kien ND, Martucci RW, Thorup SJ, Dennis PJ (1991) Development of a near anesthetic-free isolated canine hindlimb model. The effects of halothane and atropine sulfate on vascular resistance. J Pharmacol Meth 26:223â232
Ross BD (1972) Hind-limb perfusion. In: Perfusion techniques in biochemistry. A laboratory manual in the use of isolated perfused organs in biochemical experimentation. Clarendon Press, Oxford, pp 308â320
Ruderman NB, Houghton CRS, Hems R (1971) Evaluation of the isolated perfused rat hind-quarter for the study of muscle metabolism. Biochem J 124:639â651
Santiago JA, Garrison EA, Kadowith PJ (1994) Analysis of responses to bradykinin: effects of Hoe-140 in the hindquarters vascular bed of the cat. Am J Physiol 267(Heart Circ Physiol 36):H828âH836
Thimm F, Baum K (1987) Response of chemosensitive nerve fibres of group III and IV to metabolic changes in rat muscles. Pflugers Arch 410:143â152
Thimm F, Carvalho M, Babka M, Meier zu Verl E (1984) Reflex increases in heart-rate induced by perfusing the hind leg of the rat with solutions containing lactic acid. Pflugers Arch 400:286â293
Werber AH, Fink GD (1985) Continuous measurement of hindquarter resistance changes to nerve stimulation and intra-arterial drug administration in rats. J Pharmacol Meth 13:67â82
Wiegershausen B, Deptalla H (1969) Der Einfluà einiger LokalanÀsthetika auf die erregende Wirkung von Bradykinin am glatten Muskel. 1. Mitteilung: Die VerstÀrkung der vasokonstriktorischen Wirkung von Bradykinin an der isolierten Hinterpfote der Katze. Arch Int Pharmacodyn 177:278â286
Effect on Peripheral Blood Flow in Rats
Beattie DT, Beresford IJM, Connor HE, Marshall FH, Hawcock AB, Hagen RM, Bowers J, Birch PJ, Ward P (1995) The pharmacology of GR203040, a novel, potent and selective tachykinin NK1 receptor antagonist. Br J Pharmacol 116:3149â3157
Hartman JC, Olszanski DA, Hullinger TG, Brunden MN (1994) In vivo validation of a transit-time ultrasonic volume flow meter. J Pharmacol Toxicol Meth 31:153â160
Heiss WD, Traupe H (1981) Comparison between hydrogen clearance and microsphere technique for rCBF measurement. Stroke 12:161â167
Hof RP, Wyler F, Stalder G (1980) Validation studies for the use of the microsphere method in cats and young minipigs. Basic Res Cardiol 75:747â756
Lappe RW, Todt JA, Wendt RL (1986) Effect of fenoldopam on regional vascular resistance in conscious spontaneously hypertensive rats. J Pharm Exp Ther 236:187â191
Lepore DA, Kozlov AV, Stewart AG, Hurley JV, Morrison WA, Tomasi A (1999) Nitric oxide synthase-independent generation of nitric oxide in rat skeletal muscle ischemic-perfusion injury. Nitric Oxide: Biol Chem 3:75â84
Marcus ML, Heistad DD, Ehrhardt JC, Abboud FM (1976) Total and regional cerebral blood flow measurements with 7â10, 15, 25 and 50 50 ÎŒm mu;m microspheres. J Appl Physiol 40:501â507
Shaffer RA, Medvedev OS (1991) New applications of a 20-Mhz Doppler ultrasonic flowmeter. In: 7th Freiburg focus on Biomeasurement. Cardiovascular and respiratory in vivo studies. Biomesstechnik-Verlag March GmbH, 79232 March, pp 142â147
Vetterlein F, Halfter R, Schmidt G (1979) Regional blood flow determination in rats by the microsphere method during i.v. infusion of vasodilating agents. Arzneim-Forsch/Drug Res 29:747â751
Effect on Peripheral Blood Flow in Anesthetized Dogs
Buckberg GD, Luck JC, Payne DB, Hoffmann JIE, Archie JP, Fixler DE (1971) Some sources of error in measuring blood flow with radioactive microspheres. J Appl Physiol 31:589â604
Ebara T, Miura K, Okumura M, Matsuura T, Kim S, Yukimura T, Iwao H (1994) Effect of adrenomedullin on renal hemodynamics and function in dogs. Eur J Pharmacol 263:69â73
Glenny RW, Bernard S, Brinkley M (1993) Validation of fluorescent-labeled microspheres for measurement of regional organ perfusion. J Appl Physiol 74:2585â2597
Hales JRS, Cliff WJ (1977) Direct observations of the behavior of microspheres in the microvasculature. Bibliotheca Anatom 15:87â91
Prinzen FW, Glenny RW (1994) Development of non-radioactive microsphere technique for blood flow measurement. Cardiovasc Res 28:1467â1475
Raab S, Thein N, Harris AG, Messmer K (1999) A new sample-processing unit for the fluorescent microsphere method. Am J Physiol 276(Heart Circ Physiol 45):H1801âH1806
Rudolph A, Heyman MA (1967) The circulation of the fetus in utero; methods for studying distribution of cardiac output and organ blood flow. Circ Res 21:163â184
Thein E, Raab S, Harris AG, Messmer K (2000) Automation of the use of fluorescent microspheres for the determination of blood flow. Comp Meth Progr Biomed 61:11â21
Turner RA (1971) β-adrenergic blocking agents. In: Turner RA, Hebborn P (eds) Screening methods in pharmacology. vol II. Academic, New York/London, pp 21â40
Van Oosterhout MF, Willigers HM, Reneman RS (1995) Fluorescent microspheres to measure organ perfusion: validation of o simplified sample processing technique. Am J Physiol 269(Heart Circ Physiol 38):H725âH733
Effect on Peripheral Blood Supply Measured by Local Oxygen Pressure
Dawson JM, Okyayuz-Baklouti I, Hudlická O (1990) Skeletal muscle microcirculation: the effects of limited blood flow and treatment with torbafylline. Int J Microcirc Exp 9:385â400
Ehrly AM, Schroeder W (1976) Sauerstoffdruckwerte im ischaemischen Muskelgewebe von Patienten mit chronischen arteriellen VerschluÃerkrankungen. Verh Dtsch Ges Kreislaufforsch 42:380â384
Kessler M, Grunewald W (1969) Possibilities of measuring oxygen pressure fields in tissue by multiwire platinum electrodes. Progr Resp Res 3:147â152
Kessler M, Hoeper J, Krumme BA (1976) Monitoring of tissue perfusion and cellular function. Anesthesiology 45:184â197
Kunze K, Berk H (1975) Oxygen supply and muscle blood flow in normal and diseased muscle In: Kunze K, Desmedt JE (eds) Studies on neuromuscular diseases. Karger, Basel, pp 82â91
Luebbers DW, BaumgÀrtl H, Fabel H, Huch A, Kessler M, Kunze K, Riemann H, Seiler D, Schuchardt S (1969) Principle of construction and application of various platinum electrodes. Progr Resp Res 3:136â146
Effect on Mesenteric Blood Flow in Rats
Bhattacharya BK, Dadkar NK, Dohadwalla AN (1977) Vascular reactivity of perfused mesenteric vascular bed in spontaneously hypertensive and normotensive rats. Br J Pharmacol 59:243â246
Brown RA, OâConnor SE, Smith GW, Verity A (1983) The rabbit isolated arterially perfused intestinal segment preparation: a model for vascular dopamine receptors. J Pharmacol Meth 9:137â145
Chu ZM, Beilin LJ (1994) Effects of HOE 140 on systemic depressor responses to bradykinin and mesenteric vascular reactivity in vivo in pregnant WistarâKyoto rats. Clin Exp Pharmacol Physiol 21:137â140
Eikenburg DC (1984) Functional characterization of the pre- and postjunctional α-adrenoceptors in the in situ perfused rat mesenteric vascular bed. Eur J Pharmacol 105:161â165
Foy JM, Nuhu SZ (1985) Effect of three âloopâ diuretics and prostaglandins E2 & I2 on the isolated perfused rat mesenteric vasculature. Arch Int Pharmacodyn 273:237â250
Hsueh W, Gonzalez-Crussi F, Arroyave JL (1986) Release of leukotriene C4 by isolated, perfused rat small intestine in response to platelet-activating factor. J Clin Invest 78:108â114
Jackson EK, Inagami T (1990) Blockade of the pre- and postjunctional effects of angiotensin in vivo with a non-peptide angiotensin receptor antagonist. Life Sci 46:945â953
Kawasaki H, Takasaki K (1984) Vasoconstrictor response induced by 5-hydroxytryptamine released from vascular adrenergic nerves by periarterial nerve stimulation. J Pharm Exp Ther 229:816â822
Komidori H, Yamamoto R, Nickols GA, Takasaki K (1992) Characterization of the isolated rat mesenteric vascular-intestinal loop preparation. J Pharmacol Meth 27:59â65
Laher I, Triggle CR (1984) Pharmacological studies of smooth muscle from Dahl salt-sensitive and salt-resistant rats. Can J Physiol Pharmacol 62:101â104
Longhurst PA, Head JH (1985) Responses of the isolated perfused mesenteric vasculature from diabetic rats: the significance of appropriate control tissues. J Pharm Exp Ther 235:45â49
Longhurst PA, Stitzel RE, Head RJ (1986) Perfusion of the intact and partially isolated mesenteric vascular bed: application to vessels from hypertensive and normotensive rats. Blood Vessels 23:288â296
Manzini S, Perretti F (1988) Vascular effects of capsaicin in isolated perfused rat mesenteric bed. Eur J Pharmacol 148:153â159
McAdams RP (1984) The effect of temperature on the α-adrenoceptor antagonist potency of indoramin and labetalol in the rat perfused mesenteric vascular bed. J Pharm Pharmacol 36:628â629
McGregor DD (1965) The effect of sympathetic nerve stimulation on vasoconstrictor responses in perfused mesenteric blood vessels of the rat. J Physiol (London) 177:21â30
Mulavi NJ, Halpern W (1977) Contractile properties of small arterial resistance vessels in spontaneously hypertensive and normotensive rats. Circ Res 41:19â26
Nassar BA, Huang YS, McDonald ATJ, Jenkins KD, Horrobin DF (1988) The influence of phenelzine and tranylcypromine on the release of prostaglandins from the rat mesenteric vascular bed. Can J Physiol Pharmacol 66:1206â1209
Nuki C, Kawasaki H, Takasaki K, Wada A (1994) Structure-activity study of chicken calcitonin gene-related peptide (CGRP) on vasorelaxation in rat mesenteric resistance vessels. Jpn J Pharmacol 65(2):99â105
Pelissier T, Miranda HF, Bustamante D, Paeile C, Pinardi G (1992) Removal of the endothelial layer in perfused mesenteric vascular bed of the rat. J Pharmacol Meth 27:41â44
Qiu HY, Valtier B, Struyker-Boudier HAJ, Levy BI (1995) Mechanical and contractile properties of in situ localized mesenteric arteries in normotensive and spontaneously hypertensive rats. J Pharmacol Toxicol Meth 33:159â170
Randall MD, Hiley CR (1988) Effect of phenobarbitone pretreatment upon endothelium-dependent relaxation to acetylcholine in rat superior mesenteric arterial bed. Br J Pharmacol 94:977â983
Randall MD, Douglas SA, Hiley CR (1989) Vascular activities of endothelin-1 and some alanyl substituted analogues in resistance beds of the rat. Br J Pharmacol 98:685â699
Santiago JA, Osei SY, Kadowith PJ (1993) Inhibitory effects of Hoe 140 on vascular responses to bradykinin in the mesenteric vascular bed of the cat. Eur J Pharmacol 236:315â318
Santiago JA, Garrison E, Purnell WL, Smith RE, Champion HC, Coy DH, Murphy WA, Kadowitz PJ (1995) Comparison of responses to adrenomedullin and adrenomedullin analogs in the mesenteric vascular bed of the cat. Eur J Pharmacol 272:115â118
Soma M, Manku DK, Horrobin DF (1985) Prostaglandins and thromboxane outflow from the perfused mesenteric vascular bed in spontaneously hypertensive rats. Prostaglandins 29:323â333
Effect on Pulmonary Blood Flow
Baum MD, Kot PA (1972) Responses of pulmonary vascular segments to angiotensin and norepinephrine. J Thorac Cardiovasc Surg 63:322â328
Byron PR, Roberts NSR, Clark AR (1986) An isolated perfused rat lung preparation for the study aerosolized drug deposition and absorption. J Pharmaceut Sci 75:168â171
DeWitt BJ, Cheng DY, McMahon TJ, Nossaman BD, Kadowitz PJ (1994a) Analysis of responses to bradykinin in the pulmonary vascular bed of the cat. Am J Physiol Heart Circ Physiol 266:H2256âH2267
DeWitt BJ, Cheng DY, Caminiti GN, Nossaman BD, Coy DH, Murphy WA, Kadowitz PJ (1994b) Comparison of responses to adrenomedullin and calcitonin gene-related peptide in the pulmonary vascular bed of the cat. Eur J Pharmacol 257:303â306
Drake R, Gaar KA, Taylor AE (1978) Estimation of the filtration coefficient of pulmonary exchange vessels. Am J Physiol 234:H266âH274
Franks PJ, Hooper RH, Humphries RG, Jones PRM, OâConnor SE (1990) Effective pulmonary flow, aortic flow and cardiac output: in vitro and in vivo comparison in the dog. Exper Physiol 75:95â106
Heaton J, Lin B, Chang J-K, Steinberg S, Hyman A, Lippton H (1995) Pulmonary vasodilation to adrenomedullin: a novel peptide in humans. Am J Physiol 268(Heart Circ Physiol 37):H2211âH2215
Hyman AL, Kadowitz PJ, Lippton HL (1989) Methylene blue selectively inhibits pulmonary vasodilator response in cats. J Appl Physiol 66:1513â1517
Lippton HL, Nandiwada PA, Hyman AL, Kadowitz PJ (1984) Influence of cyclooxygenase blockade on responses to isoproterenol, bradykinin and nitroglycerin in the feline pulmonary vascular bed. Prostaglandins 28:253â270
Lippton H, Chang J-K, Hao Q, Summer W, Hyman AL (1994) Adrenomedullin dilates the pulmonary vascular bed in vivo. J Appl Physiol 76:2154â2156
Liu SF, Dewar A, Crawley DE, Barnes PJ, Evans TW (1992) Effect of tumor necrosis factor on hypoxic pulmonary vasoconstriction. J Appl Physiol 72:1044â1049
McMahon TJ, Kadowitz PJ (1993) Analysis of responses to substance P in the pulmonary vascular bed of the cat. Am J Physiol 264(Heart Circ Physiol 33):H394âH402
Mor L, Bomzon A, Frenkel R, Youdim MBH (1990) Angiotensin-converting enzyme activity in the isolated perfused guinea pig lung. J Pharmacol Meth 23:141â153
Nossaman BD, Feng CJ, Cheng DY, Dewitt BJ, Coy DH, Murphy WA, Kadowitz PJ (1995) Comparative effects of adrenomedullin, an adrenomedullin analog, and CGRP in the pulmonary vascular bed of the cat and the rat. Life Sci 56:63â66
Tanaka H, Tajimi K, Matsumoto A, Kobayashi K (1992) Effects of milrinone on lung water content in dogs with acute pulmonary hypertension. J Pharmacol Toxicol Meth 28:201â208
Effect on Contractile Force of Ischemic Muscle
Angersbach D, Ochlich P (1984) The effect of 7-(2â²-oxopropyl)-1,3-di-n-butyl-xanthine (BRL 30892 on ischaemic skeletal muscle pO2, pH and contractility in cats and rats. Arzneim. Forsch/Drug Res 34:1274â1278
Le Tallec N, Lacroix P, de Certaines JD, Chagneau F, Lavasseur R, Le Rumeur E (1996) Effects of dimethylformamide on in vivo fatigue and metabolism in rat skeletal muscle measured by 31P-NMR. J Pharmacol Toxicol Meth 35:139â143
Okyayuz-Baklouti I (1989) The effects of torbafylline on blood flow, pO2, and function of rat ischemic skeletal muscle. Eur J Pharmacol 166:75â86
Okyayuz-Baklouti I, Konrad-Clement S, Reifert P, Schmitt T, Schuck D (1992) Novel immobilization model in the rat: functional, histomorphological and biochemical changes in atrophying skeletal muscle. J Musc Res Mot 14:259â260
Ward A, Clissold SP (1987) Pentoxifylline, a review of its pharmacodynamic and pharmacokinetic properties. Drugs 34:50â97
Weselcouch EO, Demusz CD (1990) Drug effects on function in the ferret ischemic hindlimb. J Pharmacol Meth 23:255â264
Effect on Perfusion of Rabbit Ear (Pissemski Method)
Allen GS, Rand MJ, Story DF (1973) Techniques for studying adrenergic transmitter release in an isolated perfused artery. Cardiovasc Res 7:423â428
Aoki T, Chiba S (1993) A new cannula-inserting method for measuring vascular responsiveness. Separate intraluminal and extraluminal perfusion of canine basilar artery. J Pharmacol Toxicol Meth 29:21â27
Budai D, Buchholz JN, Duckles SP (1990) Low volume perfusion-superfusion system for measurement of transmitter release from blood vessels in vitro. J Pharmacol Meth 23:41â49
De la Lande IS, Rand MJ (1965) A simple isolated nerve-blood vessel preparation. Aust J Exp Biol Med 43:639â656
De la Lande IS, Frewin D, Waterson JG (1967) The influence of sympathetic innervation on vascular sensitivity to noradrenaline. Br J Pharmac Chemother 31:82â93
Green AF, Boura ALA (1964) Depressants of peripheral sympathetic nerve function. In: Laurence DR, Bacharach AL (eds) Evaluation of drug activities: pharmacometrics. Academic, London/New York, pp 369â430
Griesbacher T, Lembeck F (1987) Actions of bradykinin antagonists on bradykinin-induced plasma extravasation, venoconstriction, prostaglandin E2 release, nociceptor stimulation and contraction of the iris sphincter muscle of the rabbit. Br J Pharmacol 92:333â340
Krawkow NP (1913) Ãber die Wirkung von Giften auf die GefÀsse isolierter Fischkiemen. PflÃŒgerâs Arch 151:583â603
Lembeck F, Griesbacher T, Eckhardt M, Henke S, Breipohl G, Knolle J (1991) New, long-acting, potent bradykinin antagonists. Br J Pharmacol 102:297â304
Miyahara H, Imayama S, Hori Y, Suzuki H (1993) Cellular mechanisms of the steroid-induced vascular responses in the rabbit ear artery. Gen Pharmacol 24:1155â1162
Pissemski SA (1914) Ãber den Einfluss der Temperatur auf die peripherischen GefÀsse. PflÃŒgerâs Arch 156:426â442
Schlossmann H (1927) Untersuchungen ÃŒber den Adrenalingehalt des Blutes. Naunyn Schmiedebergâs Arch Exp Path Pharmakol 121:160â203
Schneider G (1935) Einfluà von Novalgin und kolloidalem Eisen auf die Odembildung am isolierten Kaninchenohr. Naunyn-Schmiedebergâs Arch exp Path Pharmakol 179:56â60
Steinsland OS, Furchgott RF, Kirpekar SM (1973) Inhibition of adrenergic transmission by parasympathicomimetics in the rabbit ear artery. J Pharmacol Exp Ther 184:346â356
Turner RA (1965) The perfused rabbit ear. In: Screening methods in pharmacology. Chapter 12: sympatholytic agents. Academic, New York/London, pp 150â151
Effect on Venous Tonus In Situ in Dogs
Rice AJ, Leeson CR, Long JP (1966) Localisation of venoconstrictor responses. J Pharmacol Exp Ther 154:539â545
General Considerations
Anidjar S, Salzmann JL, Gentric D, Lagneau P, Camilleri JP, Michel JB (1990) Elastase-induced experimental aneurysms in rats. Circulation 82:973â981
Boucher P, Gotthardt M, Li WP, Anderson RG, Herz J (2003) LRP: role in vascular wall integrity and protection from atherosclerosis. Science 3000:329â332
Brophy CM, Tilson JE, Braverman IM, Tilson MD (1988) Age of onset, pattern of distribution, and histology of aneurysm development in a genetically predisposed mouse. J Vasc Surg 8:45â48
Carrell TW, Smith A, Bumand KG (1999) Experimental techniques and models in the study of the development and treatment of abdominal aortic aneurysm. Br J Surg 86:305â312
Chiou AC, Chiu B, Pearce WH (2001) Murine aortic aneurysm produced by periarterial application of calcium chloride. J Surg Res 99:371â376
Daugherty A, Cassis LA (2004) Mouse models of abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol 24:429â434
Dobrin PB (1989) Pathophysiology and pathogenesis of aortic aneurysms. Current concepts. Surg Clin North Am 69:687â703
Dobrin PB (1999) Animal models of aneurysms. Ann Vasc Surg 13:641â648
Ernst CB (1993) Abdominal aortic aneurysm. N Engl J Med 328:1167â1172
Freestone T, Turner RJ, Higman DJ, Lever MJ, Powell JT (1997) Influence of hypercholesterolemia and adventitial inflammation on the development of aortic aneurysms in rabbits. Arterioscler Thromb Vasc Biol 17:10â17
Gertz SD, Kurgan A, Eisenberg D (1988) Aneurysms of the rabbit common carotid artery induced by periarterial application of calcium chloride in vivo. J Clin Invest 81:649â656
Herz J, Strickland DK (2001) LRP: a multifunctional scavenger and signaling receptor. J Clin Invest 108:779â784
Ishibashi S, Goldstein JL, Brown MS, Herz J, Burns DK (1994) Massive xanthomatosis and atherosclerosis in cholesterol-fed low density lipoprotein receptor-negative mice. J Clin Invest 93:1885â1893
Knowles JW, Reddick RL, Jenette JC, Smithies O, Maeda N (2000) Enhanced atherosclerosis and kidney dysfunction in eNOS(â)/(â)Apo(â)/(â) mice are ameliorated by enalapril treatment. J Clin Invest 105:451â458
Kuhlencordt PJ, Gyurko R, Han F, Scherrer-Crosbie M, Aretz TH, Hajjar R, Picard MH, Huang PL (2001) Accelerated atherosclerosis, aortic aneurysms formation, and ischemic heart disease in apolipoprotein E/endothelial nitric oxide synthase double-knockout mice. Circulation 104:44â454
Lee JK, Borhani M, Ennis TL, Upchurch GR Jr, Thompson RW (2001) Experimental abdominal aortic aneurysms in mice lacking expression of inducible nitric oxide synthase. Arterioscler Thromb Vasc Biol 21:1391â1401
Longo GW, Xiong W, Greiner TC, Zhao Y, Fiotti N, Baxter BT (2002) Matrix metalloproteinases 2 and 9 work in concert to produce aortic aneurysms. J Clin Invest 110:625â632
Maki JM, Rasanen J, Tikkanen H, Sormunen R, Makikallio K, Kivirikko KI, Soininen R (2002) Inactivation of the lysyl oxidase gene Lox leads to aortic aneurysms, cardiovascular dysfunction, and perinatal death in mice. Circulation 106:2503â2509
Nishijo N, Sugiyama F, Kimoto K, Taniguchi K, Murakami K, Suzuki S, Fukamizu A, Yagami K (1998) Salt-sensitive aortic aneurysms and rupture in hypertensive transgenic mice that overproduce angiotensin II. Lab Invest 78:1059â1066
Nomoto T, Nishina T, Tsuneyoshi H, Miwa S, Nishimura K, Komeda M (2003) Effects of two inhibitors of renin-angiotensin system on attenuation of postoperative remodeling after left ventricular aneurysm repair in rats. J Card Surg 18(Suppl 2):S61âS68
Prescott MF, Sawyer WK, Von Linden Reed J, Jeune M, Chou M, Caplan SL, Jeng AY (1999) Effect of matrix metalloproteinase inhibition on progression of atherosclerosis and aneurysm in LDL receptor-deficient mice overexpressing MMP-3, MMP-12, and MMP-13 and on restenosis in rats after balloon injury. Ann N Y Acad Sci 878:179â190
Pyo R, Lee HK, Shipley M, Curci JA, Mao D, Ziporin SJ, Ennis TL, Shapiro SD, Senior RM, Thompson RW (2000) Targeted disruption of matrix metalloproteinase-9 (gelatinase B) suppresses development of experimental aortic aneurysms. J Clin Invest 105:1641â1649
Reilly JM, Savage EB, Brophy CM, Tilson MD (1990) Hydrocortisone rapidly induces aortic rupture in a genetically susceptible mouse. Arch Surg 125:707â709
Silence J, Lupu F, Collen D, Lijnen HR (2001) Persistence of atherosclerotic plaque but reduced aneurysm formation in mice with stromelysin-1 (MMP-3) gene inactivation. Arterioscler Thromb Vasc Biol 21:1440â1445
Silence J, Collen D, Lijnen HR (2002) Reduced atherosclerotic plaque but enhanced aneurysm formation in mice with inactivation of the tissue inhibitor of metalloproteinase-1 (T1MP-1) gene. Circ Res 90:897â903
Angiotensin II-Induced Aortic Aneurysm in Mice
Daugherty A, Manning MW, Cassis LA (2000) Angiotensin II promotes atherosclerotic lesions and aneurysms in apolipoprotein E-deficient mice. J Clin Invest 195:1605â1612
Daugherty A, Manning MW, Cassis LA (2001) Antagonism of AT2 receptors augments angiotensin II-induced abdominal aortic aneurysms and atherosclerosis. Br J Pharmacol 134:865â870
Deng GG, Martin-McNulty B, Sukovich DA, Freay A, Halks- Miller M, Thinnes T, Loskutoff DJ, Carmeliet P, Dole WP, Wang YX (2003) Urokinase-type plasminogen activator plays a critical role in angiotensin II-induced abdominal aortic aneurysm. Circ Res 92:510â517
Feng Q, Song W, Lu X, Hamilton JA, Lei M, Peng T, Yee SP (2002) Development of heart failure and congenital septal defects in mice lacking endothelial nitric oxide synthase. Circulation 106:873â879
Johnston KW, Rutherford RB, Tilson MD, Shah DM, Hollier L, Stanley JC (1991) Suggested standards for reporting on arterial aneurysms: Subcommittee on Reporting Standards for Arterial Aneurysms, Ad Hoc Committee on Reporting Standards, Society for Vascular Surgery and North American Chapter, International Society for Cardiovascular Surgery. J Vasc Surg 13:452â458
Knowles JW, Reddick RL, Jenette JC, Smithies O, Maeda N (2000) Enhanced atherosclerosis and kidney dysfunction in eNOS(â)/(â)Apo(â)/(â) mice are ameliorated by enalapril treatment. J Clin Invest 105:451â458
Manning MW, Cassis LA, Huang J, Szilvassy SJ, Daugherty A (2002) Abdominal aortic aneurysms: fresh insights from a novel animal model of the disease. Vasc Med 7:45â54
Manning MW, Cassis LA, Daugherty A (2003) Differential effects of doxycycline, a broad-spectrum matrix metalloproteinase inhibitor, on angiotensin II-induced atherosclerosis and abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol 23:483â488
Martin-McNulty B, Tham DM, da Cunha V, Ho JJ, Wilson DW, Rutledge JC, Deng GG, Vergona R, Sullivan ME, Wang YX (2003) 17 β-estradiol attenuates development of angiotensin II-induced aortic abdominal aneurysm in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 23:1627â1632
Saraff K, Babamusta F, Cassis LAS, Daugherty A (2003) Aortic dissection precedes formation of aneurysms and atherosclerosis in angiotensin II-infused, apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 23:1621â1626
Song W, Lu X, Feng Q (2000) Tumor necrosis factor-alpha induces apoptosis via inducible nitric oxide synthase in neonatal mouse cardiomyocytes. Cardiovasc Res 45:595â602
Wang YX, Halks-Miller M, Vergona R, Sullivan ME, Fitch R, Mallari C, Martin-McNulty B, da Cunha V, Freay A, Rubanyi GM, Kauser K (2000) Increased aortic stiffness assessed by pulse wave velocity in apolipoprotein E-deficient mice. Am J Physiol 278:H428âH434
Wang YX, Martin-McNulty B, Feay AD, Sujowich DA, Halks- Miller M, Li AA, Vergona R, Sullivan ME, Morser J, Dole WP, Deng GG (2001) Angiotensin II increases urokinase-type plasminogen activator expression and induces aneurysms in the abdominal aorta of apolipoprotein E-deficient mice. Am J Pathol 159:1455â1464
Wang YX, Martin-McNulty B, da Cinha V, Vincelette J, Lu X, Feng Q, Hlaks-Miller M, Mahmoudo M, Schroeder M, Subramanyam B, Tseng JL, Deng GD, Schirm S, Johns A, Kauser K, Dole WP, Light DR (2005) Fasudil, a Rho-kinase inhibitor, attenuates angiotensin II-induced abdominal aortic aneurysm in apolipoprotein E-deficient mice by inhibiting apoptosis and proteolysis. Circulation 111:2219â2226
General Considerations
Babic AM, Kireeva ML, Kolesnikova TV, Lau LF (1998) CYR61, a product of a growth factor-inducible immediate early gene, promotes angiogenesis and tumor growth. Proc Natl Acad Sci U S A 95:6355â6360
Barrie R, Woltering EA, Hajarizadeh H, Mueller C, Ure T, Fletcher WS (1993) Inhibition of angiogenesis by somatostatin and somatostatin-like compounds is structurally dependent. J Surgical Res 55:446â450
Couffinhal T, Siver M, Zheng LP, Kearney M, Witzenbichler B, Isner JM (1998) Mouse model of angiogenesis. Am J Pathol 152:1667â1679
Dhanabal M, Volk R, Ramchandran R, Simons M, Sukhatme VP (1999) Cloning, expression, and in vitro activity of human endostatin. Biochem Biophys Res Commun 258:345â352
Esch F, Baird A, Ling N, Ueno N, Hill F, Denoroy L, Klepper R, Gospodarowicz D, Bohlen P, Gillemin R (1985) Primary structure of bovine pituitary basic fibroblast growth factor (FGF) and comparison with the amino-terminal sequence of bovine brain acidic FGF. Proc Natl Acad Sci U S A 82:6507â6511
Ezekowitz RA, Mulliken JB, Folkman J (1992) Interferon alfa-2a therapy for life-threatening hemangiomas in infancy. New Engl J Med 326:1456â1463
Fan TPD, Brem S (1992) In: Waring MJ, Ponder B (eds) The search for new anticancer drugs: cancer biology series, vol 3. Kluwer, Lancaster, pp 185â229
Ferrara N, Davis-Smyth T (1997) The biology of vascular endothelial growth factor. Endocr Rev 18:4â25
Fett JW, Strydom DJ, Lobb RR, Aldeman EM, Bethune JL, Riordan JF, Vallee BL (1985) Isolation and characterization of angiogenin, an angiogenic protein from human carcinoma cells. Biochemistry 24:5480â5486
Folkman J, Klagsbrun M (1987) Angiogenic factors. Science 235:442â447
Folkman J, Shing Y (1992) Angiogenesis. J Biol Chem 267:10931â10934
Good DJ, Polverini PJ, Rastinejad F, Le Beau MM, Lemons RS, Frazier WA, Bouck NP (1990) A tumor suppressor-dependent inhibitor of angiogenesis is immunologically and functionally indistinguishable from a fragment of thrombospondin. Proc Natl Acad Sci U S A 87:6624â6628
Gospodarowicz D, Bialecki H, Thakral GK (1979) The angiogenic activity of the fibroblast and epidermal growth factor. Exp Eye Res 28:501â514
Klagsbrun M, DâAmore PA (1991) Regulators of angiogenesis. Ann Rev Physiol 53:217â239
Leibovich SJ, Polverini PJ, Shepard HM, Wiseman DM, Shively V, Nuseir N (1987) Macrophage-induced angiogenesis is mediated by tumor necrosis factor alpha. Nature 329:630â632
Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N (1990) Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246:1306â1309
OâBrien ER, Garvin MR, Dev R, Stewart DK, Hinohara T, Simpson JB, Shwartz SM (1994) Angiogenesis in human coronary atherosclerotic plaques. Am J Pathol 145:883â894
OâReilly MS, Holmgren L, Shing Y, Chen C, Rosenthal RA, Moses M, Lane WS, Cao Y, Sage EH, Folkman J (1994) Angiostatin, a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 79:315â328
OâReilly MS, Holmgren L, Chen C, Folkman J (1996) Angiostatin induces and sustains dormancy of human primary tumors in mice. Nature Med 2:689â692
OâReilly MS, Boehm T, Shing Y, Fukai N, Vasios G, Lane WS, Flynn E, Birkhead JR, Olsen BR, Folkman J (1997) Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 88:277â285
Pike SE, Yao L, Jones KD, Cherney B, Appella E, Sakaguchi K, Nakhasi H, Teruya-Feldstein J, Wirth P, Gupta G, Tosato G (1998) Vasostatin, a calreticulin fragment, inhibits angiogenesis and suppresses tumor growth. J Exp Med 188:2349â2356
Schreiber AB, Winkler ME, Derynk R (1986) Transforming growth factor-alpha: a more potent angiogenic mediator than epidermal growth factor. Science 232:1251â1253
Thomas KA (1996) Vascular endothelial growth factor, a potent and selective angiogenic agent. J Biol Chem 271:603â606
Yang EY, Moses HL (1990) Transforming growth factor 1- induced changes in cell migration, proliferation, and angiogenesis in the chicken chorioallantoic membrane. J Cell Biol 111:731â741
Zhu WH, Iurlaro M, MacIntyre A, Fogel E, Nicosia RF (2003) The mouse aorta model: influence of genetic background and aging on bFG- and VEGF-induced angiogenic sprouting. Angiogenesis 6:193â199
Endothelial Cell Proliferation
Benelli U, Lepri A, Nardi M, Danesi R, Del Tacca M (1995) Tradipil inhibits endothelial cell proliferation and angiogenesis in the chick chorioallantoic membrane and in the rat cornea. J Ocular Pharmacol 11:157â166
Bussolino F, Di Renzo MF, Ziche M, Bocchietto E, Olivero M, Naldini R, Gaudino G, Tamagnone L, Coffer A, Comoglio PM (1992) Hepatocyte growth factor is a potent angiogenic growth factor which stimulates endothelial cell motility and growth. J Cell Biol 119:629â641
Cao R, Wu HL, VeitonmÀki N, Linden P, Farnebo J, Shi GY, Cao Y (1999) Suppression of angiogenesis and tumor growth by the inhibitor K1â5 generated by plasmin- mediated proteolysis. Proc Natl Acad Sci 96:5728â5733
Clapp C, Martial JA, Guzman RC, Rentier-Delrue F, Weiner RI (1993) The 16-kilodalton N-terminal fragment of human prolactin is a potent inhibitor of angiogenesis. Endocrinology 133:1292â1299
Danesi R, Agen C, Benelli U, Di Paolo A, Nardini D, Bocci G, Basolo F, Camapgni A, Del Tacca M (1997) Inhibition of angiogenesis by the somatostatin analogue octreotide acetate (SMS 201â995). Clin Cancer Res 3:265â272
Folkman J, Haundenschild CC, Zetter BR (1979) Long-term culture of capillary endothelial cells. Proc Natl Acad Sci U S A 76:5217â5221
Hu G-F (1998) Neomycin inhibits angiogenin-induced angiogenesis. Proc Natl Acad Sci U S A 95:9791â9795
Iurlaro M, Vacca A, Minischetti M, Ribatti D, Pellegrino A, Sardanelli A, Giacchetta F, Dammacco F (1998) Antiangiogenesis by cyclosporine. Exp Hematology 26:1215â1222
Oikawa T, Hasegawa M, Shimamura M, Ashino H, Murota SI, Morita I (1991) Eponemycin, a novel antibiotic, is a highly powerful angiogenesis inhibitor. Biochem Biophys Res Commun 181:1070â1076
OâReilly MS, Boehm T, Shing Y, Fukai N, Vasios G, Lane WS, Flynn E, Birkhead JR, Olsen BR, Folkman J (1997) Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 88:277â285
Pike SE, Yao L, Jones KD, Cherney B, Appella E, Sakaguchi K, Nakhasi H, Teruya-Feldstein J, Wirth P, Gupta G, Tosato G (1998) Vasostatin, a calreticulin fragment, inhibits angiogenesis and suppresses tumor growth. J Exp Med 188:2349â2356
Vacca A, Iurlaro M, Ribatti D, Minischetti M, Nico B, Ria R, Pellegrino A, Dammacco F (1999) Antiangiogenesis is produced by nontoxic doses of vinblastine. Blood 94:4143â4155
Xin X, Yang S, Kowalski J, Gerritsen ME (1999) Peroxisome proliferator-activated receptor γ ligands are potent inhibitors of angiogenesis in vitro and in vivo. J Biol Chem 274:9116â9121
Chorioallantoic Membrane Assay
Auerbach R, Kubai L, Knighton D, Folkman J (1974) A simple procedure for the long-term cultivation of chicken embryos. Dev Biol 41:391â394
Barrie R, Woltering EA, Hajarizadeh H, Mueller C, Ure T, Fletcher WS (1993) Inhibition of angiogenesis by somatostatin and somatostatin-like compounds is structurally dependent. J Surgical Res 55:446â450
Benelli U, Lepri A, Nardi M, Danesi R, Del Tacca M (1995) Tradipil inhibits endothelial cell proliferation and angiogenesis in the chick chorioallantoic membrane and in the rat cornea. J Ocular Pharmacol 11:157â166
Cao R, Wu HL, VeitonmÀki N, Linden P, Farnebo J, Shi GY, Cao Y (1999) Suppression of angiogenesis and tumor growth by the inhibitor K1â5 generated by plasmin-mediated proteolysis. Proc Natl Acad Sci 96:5728â5733
Clapp C, Martial JA, Guzman RC, Rentier-Delrue F, Weiner RI (1993) The 16-kilodalton N-terminal fragment of human prolactin is a potent inhibitor of angiogenesis. Endocrinology 133:1292â1299
Crum R, Szabo S, Folkman J (1985) A new class of steroids inhibits angiogenesis in the presence of heparin or a heparin fragment. Science 230:1375â1378
Danesi R, Agen C, Benelli U, Di Paolo A, Nardini D, Bocci G, Basolo F, Camapgni A, Del Tacca M (1997) Inhibition of angiogenesis by the somatostatin analogue octreotide acetate (SMS 201â995). Clin Cancer Res 3:265â272
Gagliardi A, Collins DC (1993) Inhibition of angiogenesis by antiestrogens. Cancer Res 53:533â535
Giannopoulou E, Katsoris P, Kardamakin D, Papadimitiou E (2003) Amifostine inhibits angiogenesis in vivo. J Pharmacol Exp Ther 304:729â737
Klauber N, Browne F, Anand-Apte B, DâAmato RJ (1996) New activity of spironolactone. Inhibition of angiogenesis in vitro and in vivo. Circulation 94:2566â2571
Iurlaro M, Vacca A, Minischetti M, Ribatti D, Pellegrino A, Sardanelli A, Giacchetta F, Dammacco F (1998) Antiangiogenesis by cyclosporine. Exp Hematology 26:1215â1222
McNatt LG, Lane D, Clark AF (1992) Angiostatic activity and metabolism of cortisol in the chorioallantoic membrane (CAM) of the chick embryo. J Steroid Biochem Molec Biol 42:687â693
McNatt LG, Weimer L, Yanni J, Clark AF (1999) Angiostatic activity of steroids in the chick embryo CAM and rabbit cornea models of neovascularization. J Ocular Pharmacol 15:413â423
Oh SJ, Jeltsch MM, BirkenhÀger R, McCarthy JEG, Weich HA, Christ B, Alitalo K, Wilting J (1997) VEGF and VEGF-C: specific induction of angiogenesis and lymphangiogenesis in the differentiated avian chorioallantoic membrane. Dev Biol 188:96â109
Oikawa T, Shimamura M (1996) Potent inhibition of angiogenesis by wortmannin, a fungal metabolite. Eur J Pharmacol 318:93â96
OâReilly MS, Boehm T, Shing Y, Fukai N, Vasios G, Lane WS, Flynn E, Birkhead JR, Olsen BR, Folkman J (1997) Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 88:277â285
Ribatti D, Urbinati C, Nico B, Rusnati M, Roncali L, Presta M (1995) Endogenous basic fibroblast growth factor is implicated in the vascularization of the chick chorioallantoic membrane. Dev Biol 170:39â49
Ribatti D, Presta M, Vacca A, Ria R, Giulani R, DellâEra P, Nico B, Roncali R, Damacco F (1999) Human erythropoietin induces a proangiogenic phenotype in cultured endothelial cells and stimulates neovascularization in vivo. Blood 93:2627â2636
Taylor S, Folkman J (1982) Protamine is an inhibitor of angiogenesis. Nature 297:307â312
Vacca A, Iurlaro M, Ribatti D, Minischetti M, Nico B, Ria R, Pellegrino A, Dammacco F (1999) Antiangiogenesis is produced by nontoxic doses of vinblastine. Blood 94:4143â4155
Vu MT, Smith CF, Burger PC, Klintworth GK (1985) An evaluation of methods to quantitate the chick chorioallantoic membrane assay in angiogenesis. Lab Invest 53:499â508
Cornea Neovascularization
Babic AM, Kireeva ML, Kolesnikova TV, Lau LF (1998) CYR61, a product of a growth factor-inducible immediate early gene, promotes angiogenesis and tumor growth. Proc Natl Acad Sci U S A 95:6355â6360
BenEzra D, Hemo I, Maftzir G (1987) The rabbit cornea. A model for the study of angiogenic factors. In: Ezra D, Ryan SJ, Glaser B, Murphy R (eds) Ocular circulation and neovascularization, Documenta Ophthalmologia proceedings, series 50. Martinus Nijhoff, Dordrecht, pp 335â340
BenEzra D, Griffin BW, Maftzir G, Aharanov O, Sharif NA, Clark AF (1997) Topical formulations of novel angiostatic steroids inhibit rabbit corneal neovascularization. Invest Ophthalmol Vis Sci 38:1954â1962
Cao R, Wu HL, Veitonmâki N, Linden P, Farnebo J, Shi GY, Cao Y (1999c) Suppression of angiogenesis and tumor growth by the inhibitor K1â5 generated by plasmin-mediated proteolysis. Proc Natl Acad Sci 96:5728â5733
Crum R, Szabo S, Folkman J (1985) A new class of steroids inhibits angiogenesis in the presence of heparin or a heparin fragment. Science 230:1375â1378
Damms T, Ross JR, Duplessie MD, Klintwort GK (1997) Intracorneal bovine albumin: an immunologic model of corneal angiogenesis. Graefeâs Arch Clin Exp Ophthalmol 235:662â666
Foschi D, Castoldi L, Corsi F, Radaelli E, Trabucchi E (1994) Inhibition of inflammatory angiogenesis in rats by locoregional administration of hydrocortisone and protamine. Agents Actions 42:40â43
Gimbrone MA, Cotran RS, Leapman SB, Folkman J (1974) Tumor growth and neo-vascularization: an experimental model using the rabbit cornea. J Nat Cancer Inst 52:413â427
Joussen AM, Kruse FE, Völcker HE, Kirchhof B (1999) Topical application of methotrexate for inhibition of corneal angiogenesis. Graefeâs Arch Clin Exp Ophthalmol 237:920â927
Kenyon BM, Voest EE, Chen CC, Flynn E, Folkman J, DâAmato RJ (1996) A model of angiogenesis in the mouse cornea. Invest Ophthalmol Vis Sci 37:1625â1632
Klauber N, Browne F, Anand-Apte B, DâAmato RJ (1996) New activity of spironolactone. Inhibition of angiogenesis in vitro and in vivo. Circulation 94:2566â2571
McNatt LG, Weimer L, Yanni J, Clark AF (1999) Angiostatic activity of steroids in the chick embryo CAM and rabbit cornea models of neovascularization. J Ocular Pharmacol 15:413â423
Xin X, Yang S, Kowalski J, Gerritsen ME (1999) Peroxisome proliferator-activated receptor γ ligands are potent inhibitors of angiogenesis in vitro and in vivo. J Biol Chem 274:9116â9121
Rat Subcutaneous Air Sac Model
Edwards JC, Sedgwick AD, Willoughby DA (1981) The formation of a structure with the features of synovial lining by subcutaneous injection of air. An in vivo tissue culture system. J Pathol 134:147â156
Funahashi Y, Wakabayashi T, Semba T, Sonoda J, Kitoh K, Yoshimatsu K (1999) Establishment of a quantitative mouse dorsal air sac model and its application to evaluate a new angiogenesis inhibitor. Oncol Res 11:319â329
Kowanko IC, Gordon TP, Rosenbilds AM, Brooks PM, Roberts- Thompson PJ (1986) The subcutaneous air pouch model of synovium and the inflammatory response to heat aggregated gammaglobulin. Agents Actions 18:421â428
Lichtenberg J, Hansen CA, Skak-Nilsen T, Bay C, Mortensen JT, Binderup L (1997) The rat subcutaneous air sac model: a new and simple method for in vivo screening of antiangiogenesis. Pharmacol Toxicol 81:280â284
Lichtenberg J, Hjarnaa PJV, Kristjansen PEG, Hansen D, Binderup L (1999) The rat subcutaneous air sac model: a quantitative assay of antiangiogenesis in induced vessels. Pharmacol Toxicol 84:34â40
Nakamura M, Katsuki Y, Shibutani Y, Oikawa T (1999) Dienogest, a synthetic steroid, suppresses both embryonic and tumor-cell-induced angiogenesis. Eur J Pharmacol 386:33â40
Schreiber AB, Winkler ME, Derynk R (1986) Transforming growth factor-α: a more potent angiogenic factor than epidermal growth factor. Science 232:1250â1253
Mesenteric Window Angiogenesis Model
Norrby K (1995) Evidence of a dual role of endogenous histamine in angiogenesis. Int J Exp Pathol 76:87â92
Norrby K, Jakobsson A, Sörbo J (1986) Mast cell-mediated angiogenesis. A novel experimental model using the rat mesentery. Virchowâs Arch B, Cell Pathol 52:195â206
Norrby K, Jakobsson A, Sörbo J (1990) Quantitative angiogenesis in spreads of intact mesenteric windows. Microvasc Res 39:341â348
Zweifach BW (1973) The microcirculation in the intestinal mesentery. Microvasc Res 5:363â367
Quantification of Vascular Endothelial Growth Factor-C
Clauss M (1998) Functions of the VEGF receptor-1 (FLT-1) in the vasculature. Trends Cardiovasc Med 8:241â245
Enholm B, Jussila L, Karkkainen M, Alitalo K (1998) Vascular endothelial growth factor-C: a growth factor for lymphatic and blood vascular endothelial cell. Trends Cardiovasc Med 8:292â297
Ferrara N, LeCouter J, Lin R, Peale F (2004) EG-VEGF and Bv8: a novel family of tissue-restricted angiogenic factors. Biochim Biophys Acta 1654:69â78
Hamada K, Oike Y, Takakura N, Ito Y, Jussila L, Dumont DJ, Alitalo K, Suda T (2000) VEGF-C signaling pathways through VEGFR-2 and VEGFR-3 in vasculoangiogenesis and hematopoiesis. Blood 96:3793â3800
Hornig C, Behn T, Bartsch W, Yayon A, Weich HA (1999) Detection and quantification of complexed and free soluble human vascular endothelial growth factor receptor-1 (sVEDFR-1) by ELISA. J Immunol Meth 226:169â177
Joukov V, Kaipainen A, Jeltsch M, Jajusola K, Olofsson B, Kumar V, Erikssan U, Alitalo K (1997) Vascular endothelial growth factors VEGF-B and VEGF-C. J Cell Physiol 1732:211â215
Kirkin V, Mazitschek R, Krishnan J, Steffen A, Waltenberger J, Pepper MS, Giannis A, Sleeman J (2001) Characterization of indolinones which preferentially inhibit VEGF-C and VEGF-D-induced activation of VEGFR-3 rather than VEGFR-2. Eur J Biochem 286:5530â5540
Rissanen TT, Markkanen JE, Gruchala M, Heikura T, Puranen A, Kettunen MI, Kholová I, Keuppinen RAS, Achan MG, Stacker SA, Alitalo K, YlÀ-Herttula S (2003) VeGF-D is the strongest angiogenesis and lymphangiogenetic factor among VEGFs delivered into skeletal muscle via adenoviruses. Circ Res 92:1098â1106
Weich HA, Bando H, Brokelmann M, Baumann P, Toi M, Barleon B, Alitalo K, Sipos B, Sleeman J (2004) Quantification of vascular endothelial growth factor-C (VEGF-C) by a novel ELISA. J Immunol Meth 285:145â155
Inhibitors of Vascular Endothelial Growth Factor
Baka S, Clamp AR, Jayson GC (2006) A review on the latest clinical compounds that inhibit VEGF in pathological angiogenesis. Expert Opin Ther Targets 10:867â876
Byrne AT, Ross L, Holash J, Nakanishi M, Hu L, Hofmann JI, Yancopoulos GD, Jaffe RB (2003) Vascular endothelial growth factor-Trap decreases tumor burden, inhibits ascites, and causes dramatic vascular remodeling in an ovarian cancer model. Clin Cancer Res 9:5721â5728
Fernandez M, Vizzutti F, Garcia-Pagan JC, Rodes J, Bosch J (2004) Anti-VEGF receptor-2 monoclonal antibody prevents portal-system collateral vessel formation in hypertensive mice. Gastrooenterology 126:886â894
Fraser HM, Wilson H, Morris KD, Swanston I, Wiegand SJ (2005) Vascular endothelial growth factor Trap suppresses ovarian function at all stages of the luteal phase in the macaque. J Clin Endocrinol Metab 90:5811â5818
Fukusawa M, Korc M (2004) Vascular endothelial growth factor-Trap suppresses tumorigenicity of multiple pancreatic cancer cell lines. Clin Cancer Res 10:3327â3332
Gingrich DE, Reddy DR, Iqbal MA, Singh J, Almone LD, Angeles TS, Albom M, Yang S, Ator MA, Meyer SL, Robinson C, Ruggeri BA, Dionne CA, Vaught JL, Mallamo JP, Hudkins RL (2003) A new class of potent vascular endothelial growth factor receptor tyrosine kinase inhibitors. Structure-activity relationships for a series of 9-alkoxymethyl-12-(3-hydroxypropyl)indeno[2,1-a]pyrrolo[3,4-c]carbazole-5-ones and the identification of CEP-52144 and its dÃmethylglycine ester prodrug clinical candidate CEP-7055. J Mol Chem 46:5375â5388
Grignani F, Kinsella T, Mencarelli A, Valtieri M, Riganelli D, Grignani F, Lanfrancone L, Peschle C, Nolan GP, Pelicci PG (1998) High-efficiency gene transfer and selection of human hematopoietic progenitor cells with a hybrid EBV/retroviral vector expressing the green fluorescence protein. Cancer Res 58:14â19
Hamma-Kourbali Y, Di Benedetto M, Ledoux D, Oudar O, Leroux Y, Lecouvey M, Kraemer M (2003) A novel non-containing-nitrogen bisphosphonate inhibits both in vitro and in vivo angiogenesis. Biochem Biophys Res Commun 310:816â823
Holash J, Davis S, Papadopoulos N, Croll SD, Ho L, Russell M, Boland P, Leidich R, Hylton D, Buorova E, Ioffe E, Huang T, Radziejewski C, Bailey K, Fandl JP, Daly T, Wiegand SJ, Yankopoulos GD, Rudge JS (2002) VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci U S A 99:11393â11398
Hood JD, Cheresh DA (2003) Building a better trap. Proc Natl Acad Sci U S A 100:8624â8625
Hu L, Hofmann J, Lu Y, Mills GB, Jaffe RB (2002) Inhibition of phosphatidylinositol 3â²-kinase increases efficacy of paclitaxel in in vitro and in vivo ovarian cancer models. Cancer Res 62:1087â1092
Hu L, Hofmann J, Holash J, Yancopoulos GD, Sood AK, Jaffe RB (2005) Vascular endothelial growth factor Trap combined with Paclitaxel strikingly inhibits tumor and ascites, prolonging survival in a human ovarian cancer model. Clin Cancer Res 11:6966â6971
Kim ES, Serur A, Huang J, Manley CA, McCrudden KW, Frischer JS, Soffer SZ, Ring L, New T, Zabski S, Rudge JS, Holash J, Yancopoulos GD, Kandel JJ, Yamashiro DJ (2002) Potent VEGF blockade causes regression of coopted vessels in a model of neuroblastoma. Proc Natl Acad Sci U S A 99:11399â11404
Lau SC, Rosa DD, Jayson G (2005) Technology evaluation: VEGF Trap (cancer). Regeneron/Sanofi-aventis. Current Opinion in Molecular Therapeutics 7(5):493â501
Roberts DM, Anderson AL, Hidaka M, Swetenburg RL, Patterson C, Stanford WL, Bautch VL (2004) A vascular gene trap screen defines RasGRP3 as an angiogenesis-regulated gene required for the endothelial response to phorbol esters. Mol Cell Biol 24:10515â10528
Rommel C, Clarke B, Zimmermann S, Nunez L, Rossman R, Reid K, Moelling K, Yancopoulos GD, Glass DJ (1999) Differentiation stage-specific inhibition of the Raf-MEKERK pathway by Akt. Science 286:1738â1741
Saishin Y, Saishin Y, Takahashi K, Lima-e-Silva R, Hylton D, Rudge JS, Wiegand SJ, Campochiaro PA (2003) VEGF-Trap (R1R2) suppresses choroidal neovascularization and VEGF-induced breakdown of the blood-retinal barrier. J Cell Physiol 195:241â248
Thurston G, Rudge JS, Ioffe E, Zhou H, Ross L, Croll SD, Glazer N, Holash J, McDonald DM, Yancopoulos G (2000) Angiopoietin-1 protects the adult vasculature against plasma leakage. Nat Med 6:460â463
Verheul HMW, Pinedo HM (2003) Vascular endothelial growth factor and its inhibitors. Drug Today 39(Suppl C):81â93
Whittles CE, Pocock TM, Wedge SR, Kendrew J, Hennequin LF, Harper SJ, Bates DO (2002) ZM32881, a novel inhibitor of vascular endothelial growth factor-receptor-2 tyrosine kinase activity. Microcirculation 9:513â522
Wulff C, Wilson H, Rudge JS, Wiegand SJ, Lunn SF, Fraser HM (2001) Luteal angiogenesis: prevention and intervention by treatment with vascular endothelial growth factor TrapA40. J Lin Endocrinol Metab 86:3377â3386
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Gralinski, M., Neves, L.A.A., Tiniakova, O. (2014). Effects on Blood Supply and on Arterial and Venous Tonus. In: Hock, F. (eds) Drug Discovery and Evaluation: Pharmacological Assays. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-27728-3_10-1
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