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Mechanisms of Cerebral Ischemic Damage

  • Chapter
Cerebral Ischemia

Part of the book series: Contemporary Neuroscience ((CNEURO))

Abstract

Stroke remains one of the major causes of death and disability throughout the world (American Heart Association, 1991). More than 80% of all strokes are a result of cerebral ischemia (Mohr et al., 1978). Global cerebral ischemia involves the entire brain and occurs during cardiac arrest or severe systemic hypotension. Focal cerebral ischemia affects restricted brain regions and occurs in a wide variety of clinical settings but is most commonly a result of cerebral vascular atherosclerosis. Focal ischemia is more frequent than global ischemia.

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References

  • Akins, P. T., Liu, P. K., and Hsu, C. Y. (1996) Immediate early gene expression in response to cerebral ischemia, friend or foe? Stroke 27, 1682–1687.

    PubMed  CAS  Google Scholar 

  • Ames, A. I., Wright, R. L., Kowada, M., Thurston, J. M., and Majno, G. (1968) Cerebral ischemia. II. The no-reflow phenomenon. Am. J. Pathol. 52, 437–453.

    Google Scholar 

  • An, G., Lin, T. N., Liu, J. S., Xue, J. J., He, Y. Y., and Hsu, C. Y. (1993) Expression of cfos and c-jun family genes after focal cerebral ischemia. Ann. Neurol. 33, 457–464.

    Google Scholar 

  • Asahi, M., Hoshimaru, M., Uemura, Y., Tokime, T., Kojima, M., Ohtsuka, T., Matsuura, N., Aoki, T., Shibahara, K., and Kikuchi, H. (1997) Expression of interleukin-1 beta converting enzyme gene family and bcl- 2 gene family in the rat brain following permanent occlusion of the middle cerebral artery. J. Cereb. Blood Flow Metab. 17, 11–18.

    PubMed  CAS  Google Scholar 

  • American Heart Association (1991) Heart and stroke facts. Dallas, TX.

    Google Scholar 

  • Astrup, J., Symon, L., Branston, N. M., and Lassen, N. A. (1977) Cortical evoked potential and extracellular K+ and H+ at critical levels of brain ischemia. Stroke 8, 51–57.

    PubMed  CAS  Google Scholar 

  • Baird, A. E., Benfield, A., Schlaug, G., Siewert, B., Lovblad, K. O., Edelman, R. R., and Warach, S. (1997) Enlargement of human cerebral ischemic lesion volumes measured by diffusion-weighted magnetic resonance imaging. Ann. Neurol. 41, 581–589.

    Google Scholar 

  • Baron, J-C., von Kummer, R., and del Zoppo, G. J. (1995) Treatment of acute ischemic stroke. Challenging the concept of a rigid and universal time window. Stroke 26, 2219–2221.

    PubMed  CAS  Google Scholar 

  • B arone, F. C., Arvin,n, B., White, R. F., Miller, A., Webb, C. L., Willette, R. N., Lysko, P. G., and Feuerstein G. Z. (1997) Tumor necrosis factor-alpha. A mediator of focal ischemic brain injury. Stroke 28, 1233–1244.

    Google Scholar 

  • Bazan, N. G. (1989) Arachidonic acid in the modulation of excitable membrane function and at the onset of brain damage. Ann. NY. Acad. Sci. 559, 1–16.

    PubMed  CAS  Google Scholar 

  • Bazan, N. G., Fletcher, B. S., Herschman, H. R., and Mukherjee, P. K. (1994) Plateletactivating factor and retinoic acid synergistically activate the inducible prostaglandin synthase gene. Proc. Natl. Acad. Sci. USA 91, 5252–5256.

    PubMed  CAS  Google Scholar 

  • Benveniste, H., Drejer, J., Schousboe, A., and Diemer, N. H. (1984) Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis. J. Neurochem.43, 1369–1374.

    Google Scholar 

  • Biller, J., Patrick, J. T., Shepard, A., and Adams, H. P. (1993) Delay time between onset of ischemic stroke and hospital arrival. J. Stroke Cerebrovasc. Dis. 3, 228.230.

    Google Scholar 

  • Bowes, M. P., Rothlein, R., Fagan, S. C., and Zivin, J. A. (1995) Monoclonal antibodies preventing leukocyte activation reduce experimental neurologic injury and enhance efficacy of thrombolytic therapy. Neurology 45, 815–819.

    Google Scholar 

  • Braquet, P., Spinnewyn, B., Demerle, C., Hosford, D., Marcheselli, V., Rossowska, M., and Bazan, N. G. (1989) The role of platelet-activating factor in cerebral ischemia and related disorders. Ann. NY. Acad. Sci. 559, 296–312.

    Google Scholar 

  • Cao, W, Carney, J. M., Duchon, A., Floyd, R. A., and Chevion, M. (1988) Oxygen free radical involvement in ischemia and reperfusion injury to brain. Neurosci. Lett. 88, 233–238.

    PubMed  CAS  Google Scholar 

  • Chan, P. H. (1996) Role of oxidants in ischemic brain damage. Stroke 27, 1124–1129.

    PubMed  CAS  Google Scholar 

  • Charriaut-Marlangue, C., Margaill, I., Plotkine, M., and Ben-Ari, Y. (1995) Early endonuclease activation following reversible focal ischemia in the rat brain. J. Cereb. Blood Flow Metab. 15, 385–388.

    Google Scholar 

  • Chen, H., Chopp, M., Schultz, L., Bodzin, G., and Garcia, J. H. (1993) Sequential neuronal and astrocytic changes after transient middle cerebral artery occlusion in the rat. J. Neurol. Sci. 118, 109–106.

    Google Scholar 

  • Chen, J., Graham, S. H., Chan, P. H., Lan, J., Zhou, R. L., and Simon, R. P. (1995) bcl-2 is expressed in neurons that survive focal ischemia in the rat. Neuroreport 6, 394–398.

    Google Scholar 

  • Chen, M., Chopp, M., and Bodzin, G. (1992) Neutropenia reduces the volume of cerebral infarct after transient middle cerebral artery occlusion in the rat. Neurosci. Res. Comun. 11, 93–99.

    Google Scholar 

  • Choi, D. W. (1985) Glutamate neurotoxicity in cortical cell culture is calcium dependent. Neurosci. Lett. 58, 293–297.

    PubMed  CAS  Google Scholar 

  • Choi, D. W. (1990) Cerebral hypoxia: Some new approaches and unanswered questions. J. Neurosci. 10, 2493–2501.

    PubMed  CAS  Google Scholar 

  • Chopp, M., Zhang, R. L., Chen, H., Li, Y., Jiang, N., and Rusche, J. R. (1994) Postischemic administration of an anti-Mac-1 antibody reduces ischemic cell damage after transient middle cerebral artery occlusion in rats. Stroke 25, 869–875.

    PubMed  CAS  Google Scholar 

  • Cino, M., and Del, M. R. (1989) Generation of hydrogen peroxide by brain mitochondria: the effect of reoxygenation following postdecapitative ischemia. Arch. Biochem. Biophys. 269, 623–638.

    PubMed  CAS  Google Scholar 

  • Clark, R. K., Lee, E. V., Fish, C. J., White, R. F., Price, W. J., Jonak, Z. L., and Feuerstein, G. Z. (1993) Development of tissue damage, inflammation and resolution following stroke: an immunohistochemical and quantitative planimetric study. Brain Res. Bull. 31, 565–572.

    CAS  Google Scholar 

  • Clark, W. M., Madden, K. P., Rothlein, R., and Zivin, J. A. (1991) Reduction of central nervous system ischemic injury in rabbits using leukocyte adhesion antibody treatment. Stroke 22, 877–883.

    Google Scholar 

  • Cole, D. J., Drummond, J. C., Patel, P. M., and Reynolds, L. R. (1997) Hypervolemichemodilution during cerebral ischemia in rats: effect of diaspirin cross-linked hemoglobin (DCLHb) on neurologic outcome and infarct volume. J. Neurosurg. Anesthesiol. 9, 44–50.

    Google Scholar 

  • Coles, J. C., Ahmed, S. N., Mehta, H. U., and Kaufmann, J. C. (1986) Role of free radical scavenger in protection of spinal cord during ischemia. Ann. Thorac. Surg. 41, 551–556.

    PubMed  CAS  Google Scholar 

  • Crumrine, R. C., Thomas, A. L., and Morgan, P. F. (1994) Attenuation of p53 expression protects against focal ischemic damage in transgenic mice. J. Cereb. Blood Flow Metab. 14, 887–891.

    PubMed  CAS  Google Scholar 

  • Del Zoppo, G. J. (1997) Reperfusion damage: The role of P. M. N. leukocytes, in Primer on Cerebrovascular Diseases (Welsh M., Caplan L., Siësjo B., Weir B. and Reis, D. J., eds), Academic San Diego, CA, pp. 217–220.

    Google Scholar 

  • Del Zoppo, G. J., Schmid-Schonbein, G. W., Mori, E., Copeland, B. R., and Chang, C. M. (1991) Polymorphonuclear leukocytes occlude capillaries following middle cerebral artery occlusion and reperfusion in baboons. Stroke 22, 1276–1283.

    PubMed  Google Scholar 

  • Demopoulos, H. B., Flamm, E. S., Seligman, M. L., Jorgensen, E., and Ransohoff, J. (1977) Antioxidant effects of barbiturates in model membranes undergoing free radical damage. Acta. Neurol. Scand. Suppl. 64, 152–153.

    PubMed  CAS  Google Scholar 

  • Dereski, M. O., Chopp, M., Knight, R. A., Rodolosi, L. C., and Garcia, J. H. (1993) The heterogeneous temporal evolution of focal ischemic neuronal damage in the rat. Acta. Neuropathol. 85, 327–333.

    PubMed  CAS  Google Scholar 

  • Du, C., Hu, R., Csernansky, C. A., Liu, X. Z., Hsu, C. Y., and Choi, D. W. (1996) Additive neuroprotective effects of dextrorphan and cycloheximide in rats subjected to transient focal cerebral ischemia. Brain Res. 718, 233–236.

    PubMed  CAS  Google Scholar 

  • Estol, C. J., and Pessin, M. S. (1990) Anticoagulation: is there still a role in atherothrombotic stroke? Stroke 21, 820–824.

    PubMed  CAS  Google Scholar 

  • Feeney, D. M. (1997) From laboratory to clinic: noradrenergic enhancement of physical therapy for stroke or trauma patients. Adv. Neurol. 73, 383–394.

    PubMed  CAS  Google Scholar 

  • Feuerstein, G., and Miller, A. (1997) Vasoactive mediators of cerebral vessels, in Primer on Cerebrovascular Diseases (Welsh M., Caplan L., Siësjo B., Weir B. and Reis D. J.; eds), Academic, San Diego, CA pp. 8–13.

    Google Scholar 

  • Feuerstein, G. Z., Wang, X., and Barone, F. C. (1998) Inflammatory mediators and brain injury: the role of cytokines and chemokines in stroke and CNS diseases, in Cerebrovascular Diseases (Ginsberg M. D., and Bogousslavsky J., eds.), Blackwell, Cambridge, MA, pp. 507–531.

    Google Scholar 

  • Flamm, E. S., Demopoulos, H. B., Seligman, M. L., and Ransohoff, J. (1977) Possible molecular mechanisms of barbiturate-mediated protection in regional cerebral ischemia. Acta. Neurol. Scand. Suppl. 64, 150–151.

    Google Scholar 

  • Garcia, J. H., Liu, K. F., and Ho, K. L. (1995) Neuronal necrosis after middle cerebral artery occlusion in Wistar rats progresses at different time intervals in the caudoputamen and the cortex. Stroke 26, 636–642.

    PubMed  CAS  Google Scholar 

  • Garcia, J. H., Liu, K. F., Yoshida, Y., Chen, S., and Lian, J. (1994a) Brain microvessels: factors altering their patency after the occlusion of a middle cerebral artery (Wistar rat). Am. J. Pathol. 145, 728–740.

    Google Scholar 

  • Garcia, J. H., Liu, K. F., Yoshida, Y., Lian, J., Chen, S., and del Zoppo, G. J. (1994b) Influx of leukocytes and platelets in an evolving brain infarct. Am. J. Pathol. 144, 188–199.

    Google Scholar 

  • Garcia, J. H., Yoshida, Y., Chen, H., Li, Y., Zhang, Z. G., Lian, J., Chen, S., and Chopp, M. (1993) Progression from ischemic injury to infarct following middle cerebral artery occlusion in the rat. Am. J. Pathol. 142, 623–635.

    Google Scholar 

  • Garthwaite, G., and Garthwaite, J. (1986) Amino acid neurotoxicity: intracellular sites of calcium accumulation associated with the onset of irreversible damage to rat cerebellar neurones in vitro. Neurosci. Lett. 71, 53–58.

    Google Scholar 

  • Giffard, R. G., Monyer, H., Christine, C. W., and Choi, D. W. (1990) Acidosis reduces NMDA receptor activation, glutamate neurotoxicity, and oxygen-glucose deprivation neuronal injury in cortical cultures. Brain Res. 506, 339–342.

    PubMed  CAS  Google Scholar 

  • Gillardon, F., Lenz, C., Waschke, K. F., Krajewski, S., Reed, J. C., Zimmermann, M., and Kuschinsky, W. (1996) Altered expression of Bcl-2, Bcl-X, Bax, and c-Fos colocalizes with DNA fragmentation and ischemic cell damage following middle cerebral artery occlusion in rats. Brain Res. Mol. Brain Res. 40, 254–260.

    Google Scholar 

  • Ginsberg, M. D., Globus, M., Busto, R., and Dietrich, W. D. (1990) The potential of combination pharmacotherapy in cerebral ischemia, in Pharmacology of cerebral ischemia (Krieglstein J. and Oberpichler H., eds), Wissenschaftliche Verlagsgesellschaft, Stuttgard, pp. 499–510.

    Google Scholar 

  • Ginsberg, M. D., Sternau, L. L., Globus, M. Y., Dietrich, W. D., and Busto, R. (1992) Therapeutic modulation of brain temperature: relevance to ischemic brain injury. Cerebrovasc Brain Metab. Rev. 4, 189–225.

    Google Scholar 

  • Giulian, D. (1997) Reactive microglia and ischemic injury. in: Primer on Cerebrovascular Diseases (Welsh M., Caplan L., Siësjo B., Weir B. and Reis D. J., eds), San Diego, CA, Academic pp 117–124.

    Google Scholar 

  • Giulian, D., Corpuz, M., Chapman, S., Mansouri, M., and Robertson, C. (1993) Reactive mononuclear phagocytes release neurotoxins after ischemic and traumatic injury to the central nervous system. J. Neurosci. Res. 36, 681–693.

    Google Scholar 

  • Globus, M. Y., Busto, R., Dietrich, W. D., Martinez, E., Valdes, I., and Ginsberg, M. D. (1988) Effect of ischemia on the in-vivo release of striatal dopamine, glutamate, and gamma-aminobutyric acid studied by intracerebral microdialysis. J. Neurochem. 51, 1455–1464. Goldman, S. A., Pulsinelli, W. A., Clarke, W. Y., Kraig, R. P., and Plum, F. (1989) The effects of extracellular acidosis on neurons and glia in vitro. J. Cereb. Blood Flow Metab. 9, 471–477. Grandati, M., Verrecchia, C., Revaud, M. L., Allix, M., Boulu, R. G., and Plotkine, M. (1997) NO-synthase activities and nitric oxide production in mice following transient focal cerebral ischemia. J. Cereb. Blood Flow Metab. 17, S94. Hakim, A. M. (1987) The cerebral ischemic penumbra. Can. J. Neurol. Sci. 14, 557–559. Hakim, A. M., and Shoubridge, E. A. (1989) Cerebral acidosis in focal ischemia. Cerebrovasc. Brain Metab. Rev. 1, 115–132. Hall, E. D., Pazara, K. E., and Braughler, J. M. (1988) 21-Aminosteroid lipid peroxidation inhibitor U74006F protects against cerebral ischemia in gerbils. Stroke 19, 997–1002. Hanaway, J., Torack, R., Fletcher, A. P., and Landau, W. M. (1976) Intracranial bleeding associated with urokinase therapy for acute ischemic hemispheral stroke. Stroke 7, 143–146. Hansen, A. J. (1985) Effect of anoxia on ion distribution in the brain. Physiol. Rev. 65, 101–148. Hara, H., Fink, K., Endres, M., Friedlander, R. M., Gagliardini, V., Yuan, J., and Moskowitz, M. A. (1997a) Attenuation of transient focal cerebral ischemic injury in transgenic mice expressing a mutant ICE inhibitory protein. J. Cereb. Blood Flow. Metab. 17, 370–375. Hara, H., Friedlander, R. M., Gagliardini, V., Ayata, C., Fink, K., Huang, Z., Shimizu, S. M., Yuan, J., and Moskowitz, M. A. (1997b) Inhibition of interleukin lbeta converting enzyme family proteases reduces ischemic and excitotoxic neuronal damage. Proc. Natl. Acad. Sci. USA 94, 2007–2012. Harris, R. J., Symon, L., Branston, N. M., and Bayhan, M. (1981) Changes in extracellular calcium activity in cerebral ischaemia. J. Cereb. Blood Flow Metab. 1, 203–209. Heiss, W-D., Huber, M., Fink, G. R., Herloz, K., Pietrzyk, U., Wagner, R., and Weinhard, K. (1992) Progressive derangement of periinfarct viable tissue in ischemic stroke. J. Cereb. Blood Flow Metab. 12, 193–203. Heiss, W. D., and Rosner, G. (1983) Functional recovery of cortical neurons as related to degree and duration of ischemia. Ann. Neurol. 14, 294–301. Herdegen, T., Skene, P., and Bahr, M. (1997) The c-Jun transcription factor―bipotential mediator of neuronal death, survival and regeneration. Trends Neurosci. 20, 227–231. Hossmann, K-A. (1993) Ischemia-mediated neuronal injury. Resuscitation. 26, 225–235. Hossmann K-A. (1994a) Glutamate-mediated injury in focal cerebral ischemia: the excitotoxin hypothesis revised. Brain Pathol.> 4, 23–36. Hossmann, K-A. (1994b) Viability thresholds and the penumbra of focal ischemia. Ann. Neurol. 36, 557–565. Hossmann, K-A., and Kleihues, P. (1973) Reversibility of ischemic brain damage. Arch. Neurol. 29, 375–384.

    Google Scholar 

  • Hsu, C. Y., Liu, T. H., Xu, J., Hogan, E. L., Chao, J., Sun, G., Tai, H. H., Beckman, J. S., and Freeman, B. A. (1989) Arachidonic acid and its metabolites in cerebral ischemia. Ann. NYAcad. Sci. 559, 282–295.

    Google Scholar 

  • ladecola, C. (1997) Bright and dark sides of nitric oxide in ischemic brain damage. Trends Neurosci. 20, 132–138.

    Google Scholar 

  • Iadecola, C. (1998) Cerebral circulatory dysregulation in ischemia, in Cerebrovascular Diseases (Ginsberg M. D., and Bogousslavsky J., eds.), Blackwell, Cambridge, MA, pp. 319–332.

    Google Scholar 

  • Iadecola, C., Xu, X., Zhang, F., El-Fakahany, E. E., and Ross, M. E. (1995a) Marked induction of calcium-independent nitric oxide synthase activity after focal cerebral ischemia. J. Cereb. Blood Flow Metab. 14, 52–59.

    Google Scholar 

  • Iadecola, C., Zhang, F., Casey, R., Clark, H. B., and Ross, M. E. (1996) Inducible nitric oxide synthase gene expression in vascular cells following transient focal cerebral ischemia. Stroke 27, 1373–1380.

    Google Scholar 

  • Iadecola, C., Zhang, F., Nogawa, S., and Ross, M. E. (1998) Post-ischemic gene expression and cerebral ischemic damage: Role of inducible nitric oxide synthase. in: Frontiers in Cerebrovascular Disease: Mechanisms, Diagnosis and Treatment (Robertson, J. T. and Nowak,T. S., eds.), New York, Futura Publications, pp. 299–313.

    Google Scholar 

  • Iadecola, C., Zhang, F., and Xu, X. (1995b) Inhibition of inducible nitric oxide synthase ameliorates cerebral ischemic damage. Am. J. Physiol. 268, R286-R292.

    Google Scholar 

  • Iadecola, C., Zhang, F., Xu, X., Casey, R., and Ross, M. E. (1995c) Inducible nitric oxide synthase gene expression in brain following focal cerebral ischemia. J. Cereb. Blood Flow Metab. 15, 378–384.

    Google Scholar 

  • Jacewicz, M., Kiessling, M., and Pulsinelli, W. A. (1986) Selective gene expression in focal cerebral ischemia. J. Cereb. Blood Flow Metab. 6, 263–272.

    PubMed  CAS  Google Scholar 

  • Johansen, F. F., Jorgensen, M. B., and Diemer, N. H. (1986) Ischemic, CA-1 pyramidal cell loss is prevented by preischemic colchicine destruction of dentate gyrus granule cells. Brain Res. 377, 344–347.

    PubMed  CAS  Google Scholar 

  • Kalaria, R. N., Bhatti, S. U., Palatinsky, E. A., Pennington, D. H., Shelton, E. R., Chan, H. W., Perry, G., and Lust, W. D. (1993) Accumulation of the beta amyloid precursor protein at sites of ischemic injury in rat brain. Neuroreport. 4, 211–214.

    PubMed  CAS  Google Scholar 

  • Kass, I. S., and Lipton, P. (1982) Mechanisms involved in irreversible anoxic damage to the in vitro rat hippocampal slice. J. Physiol. 332, 459–472.

    PubMed  CAS  Google Scholar 

  • Kawamata, T., Dietrich, W. D., Schallert, T., Gotts, J. E., Cocke, R. R., Benowitz, L. I., and Finlestein, S. P. (1997) Intracisternal basic fibroblast growth factor enhances functional recovery and up-regulates the expression of a molecular marker of neuronal sprouting following focal cerebral infarction. Proc. Natl. Acad. Sci. USA 94, 8179–8184.

    Google Scholar 

  • Kiessling, M., and Gass, P. (1994) Stimulus-transcription coupling in focal cerebral ischemia. Brain Pathol. 4, 77–83.

    PubMed  CAS  Google Scholar 

  • Kim, J. S. (1996) Cytokines and adhesion molecules in stroke and related diseases. J. Neurol. Sci. 137, 69–78.

    PubMed  CAS  Google Scholar 

  • Kinouchi, H., Epstein, C. J., Mizui, T., Carlson, E., Chen, S. F., and Chan, P. H. (1991) Attenuation of focal cerebral ischemic injury in transgenic mice overexpressing CuZn superoxide dismutase. Proc. Natl. Acad. Sci. USA 88, 11,158–11,162.

    Google Scholar 

  • Kinouchi, H., Sharp, F R., Hill, M. P., Koistinaho, J., Sagar, S. M., and Chan, P. H. (1993) Induction of 70-kDa heat shock protein and hsp70 mRNA following transient focal cerebral ischemia in the rat. J. Cereb. Blood Flow Metab. 13, 105–115.

    Google Scholar 

  • Kochanek, P. M., and Hallenbeck, J. M. (1992) Polymorphonuclear leukocytes and monocyte/macrophages in the pathogenesis of cerebral ischemia and stroke. Stroke 23, 1367–1379.

    PubMed  CAS  Google Scholar 

  • Koistinaho, J., and Hokfelt, T. (1997) Altered gene expression in brain ischemia. Neuroreport 8, i-viii.

    Google Scholar 

  • Kondo, T., Reaume, A. G., Huang, T-T., Carlson, E., Murakami, K., Chen, S. F., Hoffman, E. K., Scott R. W., Epstein C. J., and Chan P. H. (1997) Reduction of CuZnsuperoxide dismutase activity exacerbates neuronal cell injury and edema formation after transient focal cerebral ischemia. J. Neurosci. 17, 4180–4189.

    Google Scholar 

  • Koroshetz, W. J., and Moskowitz, M. A. (1996) Emerging treatments for stroke in humans. Trends Pharmacol. Sci. 17, 227–233.

    Google Scholar 

  • Kovacs, Z., Ikezaki, K., Samoto, K., Inamura, T., and Fukui, M. (1996) VEGF and flt. Expression time kinetics in rat brain infarct. Stroke 27, 1865–1872.

    PubMed  CAS  Google Scholar 

  • Kraig, R. P., Petito, C. K., Plum, F., and Pulsinelli, W. A. (1987) Hydrogen ions kill brain at concentrations reached in ischemia. J. Cereb. Blood Flow Metab. 7, 379–386.

    PubMed  CAS  Google Scholar 

  • Krupinski, J., Issa, R., Bujny, T., Slevin, M., Kumar, P., Kumar, S., and Kaluza, J. (1997) A putative role for platelet-derived growth factor in angiogenesis and neuroprotection after ischemic stroke in humans. Stroke 28, 564–573.

    Google Scholar 

  • Krupinski, J., Kaluza, J., Kumar, P., Kumar, S., and Wang, J. M. (1994) Role of angiogenesis in patients with cerebral ischemic stroke. Stroke 25, 1794–1798.

    Google Scholar 

  • Krupinski, J., Kaluza, J., Kumar, P., Wang, M., and Kumar, S. (1993) Prognostic value of blood vessel density in ischaemic stroke. Lancet 342, 742.

    Google Scholar 

  • Lascola, C. D., and Kraig, R. P. (1997) Astrocyte reaction in global ischemic brain injury. in: Primer on Cerebrovascular Diseases (Welsh M., Caplan L., Siesjo B., Weir B. and Reis D. J., eds.), San Diego, CA, Academic, pp. 114–117.

    Google Scholar 

  • Li, Y., Chopp, M., Jiang, N., Yao, F., and Zaloga, C. (1995) Temporal profile of in situ DNA fragmentation after transient middle cerebral artery occlusion in the rat. J. Cereb. Blood Flow Metab. 15, 389–397.

    PubMed  CAS  Google Scholar 

  • Li, Y., Chopp, M., Zhang, Z. G., Zaloga, C., Niewenhuis, L., and Gautam, S. (1994) p53-immunoreactive protein and p53 mRNA expression after transient middle cerebral artery occlusion in rats. Stroke 25, 849–855.

    Google Scholar 

  • Linnik, M. D., Zobrist, R. H., and Hatfield, M. D. (1993) Evidence supporting a role for programmed cell death in focal cerebral ischemia in rats. Stroke 24, 2002–2009.

    Google Scholar 

  • Linnik, M. D., Zahos, P., Geschwind, M. D., and Federoff, H. J. (1995) Expression of bcl-2 from a defective herpes simplex virus-1 vector limits neuronal death in focal cerebral ischemia. Stroke 26, 1670–4; 1675.

    Google Scholar 

  • Liu, T. H., Beckman, J. S., Freeman, B. A., Hogan, E. L., and Hsu, C. Y. (1989) Polyethylene glycol-conjugated superoxide dismutase and catalase reduce ischemic brain injury. Am. J. Physiol. H589–593.

    Google Scholar 

  • Loddick, S. A., MacKenzie, A., and Rothwell, N. J. (1996) An ICE inhibitor, z-VAD-DCB attenuates ischaemic brain damage in the rat. Neuroreport7, 1465–1468.

    Google Scholar 

  • Loddick, S. A., and Rothwell, N. J. (1996) Neuroprotective effects of human recombi-nant interleukin-1 receptor antagonist in focal cerebral ischemia in the rat. J. Cereb. Blood Flow Metab. 16, 932–940.

    PubMed  CAS  Google Scholar 

  • Lyden, P. D., Grotta, J. C., Levine, S. R., Marler, J. R., Frankel, M. R., and Brott, T. G. (1997) Intravenous thrombolysis for acute stroke. Neurology 49, 14–20.

    PubMed  CAS  Google Scholar 

  • Macfarlane, R., Tasdemiroglu, E., Moskowitz, M. A., Uemura, Y., Wei, E. P., and Kontos, H. A. (1991) Chronic trigeminal ganglionectomy or topical capsaicin application to pial vessels attenuates postocclusive cortical hyperemia but does not influence postis-chemic hypoperfusion. J. Cereb. Blood Flow Metab. 11, 261–271.

    Google Scholar 

  • MacManus, J. P., Buchan, A. M., Hill, I. E., Rasquinha, I., and Preston, E. (1993) Global ischemia can cause DNA fragmentation indicative of apoptosis in rat brain. Neurosci. Lett. 164, 89–92.

    Google Scholar 

  • MacManus, J. P., Hill, I. E., Preston, E., Rasquinha, I., Walker, T., and Buchan, A. M. (1995) Differences in DNA fragmentation following transient ischemia or decapita-tion ischemia in rats. J. Cereb. Blood Flow Metab. 15, 728–737.

    Google Scholar 

  • MacManus, J. P., and Linnik, M. D. (1997) Gene expression induced by cerebral ischemia: an apoptotic perspective. J. Cereb. Blood Flow Metab. 17, (in press).

    Google Scholar 

  • Malinski, T., Bailey, F., Zhang, Z. G., and Chopp, M. (1993) Nitric oxide measured by a porphyrinic microsensor in rat brain after transient middle cerebral artery occlusion. J. Cereb Blood Flow Metab. 13, 355–358.

    PubMed  CAS  Google Scholar 

  • Marchal, G., Beaudouin, V., Rioux, P., de la Sayette, V., Le Doze, F., Viader, F., Derlon, J-M., and Baron, J-C. (1996) Prolonged persistence of substantial volumes of potentially viable brain tissue after stroke. Stroke 27, 599–606.

    PubMed  CAS  Google Scholar 

  • Martinou, J. C., Dubois, D. M., Staple, J. K., Rodriguez, I., Frankowski, H., Missotten, M., Albertini, P., Talabot, D., Catsicas, S., Pietra, C., et al (1994) Overexpression of BCL-2 in transgenic mice protects neurons from naturally occurring cell death and experimental ischemia. Neuron 13, 1017–1030.

    PubMed  CAS  Google Scholar 

  • Massa, S. M., Swanson, R. A., and Sharp, F. R. (1996) The stress gene response in brain. Cerebrovasc. Brain Metab. Rev. 8, 95–158.

    Google Scholar 

  • Matsuo, Y., Onodera, H., Shiga, Y., Nakamura, M., Ninomiya, M., Kihara, T., and Kogure, K. (1994) Correlation between myeloperoxidase-quantified neutrophil accumulation and ischemia brain injury in the rat. Stroke 25, 1469–1475.

    PubMed  CAS  Google Scholar 

  • Mies, G., Ishimaru, S., Xie, Y., Seo, K., and Hossmann, K. A. (1991) Ischemic thresholds of cerebral protein synthesis and energy state following middle cerebral artery occlusion in rat. J. Cereb. Blood Flow Metab. 11, 753–761.

    PubMed  CAS  Google Scholar 

  • Mohamed, A. A., Gotoh, O., Graham, D. I., Osborne, K. A., McCulloch, J., Mendelow, A. D., Teasdale, G. M., and Harper, A. M. (1985) Effect of pretreatment with the calcium antagonist nimodipine on local cerebral blood flow and histopathology after middle cerebral artery occlusion. Ann. Neurol. 18, 705–711.

    Google Scholar 

  • Mohr, J. P., Caplan, L. R., Melski, J. W., Goldstein, R. J., Duncan, G. W., Kistler, J. P., Pessin, M. S., and Bleich, H. L. (1978) The Harvard Cooperative Stroke Registry: a prospective registry. Neurology 28, 754–762.

    PubMed  CAS  Google Scholar 

  • Monyer, H., Hartley, D. M., and Choi, D. W. (1990) 21-Aminosteroids attenuate excitotoxic neuronal injury in cortical cell cultures. Neuron 5, 121–126.

    Google Scholar 

  • Morioka, T., Kalehua, A. N., and Streit, W. J. (1993) Characterization of microglial reaction after middle cerebral artery occlusion in the rat brain. J. Comp. Neurol. 327, 123–132. Morley, P., Hogan, J. H., and Hakim, A. M. (1994) Calium-mediated mechanisms of ischemc injury and protection. Brain Patho. 4, 37–47. Nedergaard, M. (1988) Mechanisms of brain damage in focal cerebral ischemia. Acta. Neurologica. Scandinavica. 77, 1–24. Nedergaard, M., and Hansen, A. J. (1993) Characterization of cortical depolarizations evoked in focal cerebral ischemia. J. Cereb. Blood Flow Metab. 13, 568–74. Nedergaard, M., Jakobsen, J., and Diemer, N. H. (1988) Autoradiographic determination of cerebral glucose content, blood flow, and glucose utilization in focal ischemia of the rat brain: influence of the plasma glucose concentration. J. Cereb. Blood Flow Metab. 8, 100–108. Nicholson, C., Bruggencate, G. T., Steinberg, R., and Stockle, H. (1977) Calcium modulation in brain extracellular microenvironment demonstrated with ion-selective micropipette. Proc. Natl. Acad. Sci. USA 74, 1287–1290. Nogawa, S., Zhang, F., Ross, E., and Iadecola, C. (1997) Cyclooxygenase-2 gene expression in neurons contributes to ischemic brain damage. J. Neurosci. 17, 2746–2755. Nordstrom, C. H., and Siesjo, B. K. (1978) Effects of phenobarbital in cerebral ischemia. Part I: cerebral energy metabolism during pronounced incomplete ischemia. Stroke 9, 327–335. Nowak, T. S., and Jacewicz, M. (1994) The heat shock/stress response in focal cerebral ischemia. Brain Pathol 4, 67–76. Olney, J. W. (1969) Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate. Science 164, 719–721. Onodera, H., Sato, G., and Kogure, K. (1986) Lesions to Schaffer collaterals prevent ischemic death of CA1 pyramidal cells. Neurosci. Lett. 68, 169–174. Rehncrona, S., Folbergrova, J., Smith, D. S., and Siesjo, B. K. (1980) Influence of complete and pronounced incomplete cerebral ischemia and subsequent recirculation on cortical concentrations of oxidized and reduced glutathione in the rat. J. Neurochem. 34, 477–486. Rehncrona, S., Hauge, H. N., and Siesjo, B. K. (1989) Enhancement of iron-catalyzed free radical formation by acidosis in brain homogenates: differences in effect by lactic acid and CO2. J. Cereb. Blood Flow Metab. 9, 65–70. Ren, J. M., and Finklestein, S. P. (1997) Trophic factor treatment for stroke. in: Primer on Cerebrovascular Diseases (Welsh M., Caplan L., Siesjo B., Weir B. and Reis, D. J., eds.), Academic, San Diego, CA, pp. 34–37. Rothman, S. (1984) Synaptic release of excitatory amino acid neurotransmitter mediates anoxic neuronal death. J. Neurosci. 4, 1884–1891. Rothman, S. M. (1983) Synaptic activity mediates death of hypoxic neurons. Science 220, 536–537. Salgado, A. V., Jones, S. C., FurIan, A. J., Korfali, E., Marshall, S. A., and Little, J. R. (1989) Bimodal treatment with nimodipine and low-molecular-weight dextran for focal cerebral ischemia in the rat. Ann. Neurol. 26, 621–627.

    Google Scholar 

  • Morioka, T., Kalehua, A. N., and Streit, W. J. (1993) Characterization of microglial reaction after middle cerebral artery occlusion in the rat brain. J. Comp. Neurol. 327, 123–132.

    Google Scholar 

  • Morley, P., Hogan, J. H., and Hakim, A. M. (1994) Calium-mediated mechanisms of ischemc injury and protection. Brain Patho. 4, 37–47.

    CAS  Google Scholar 

  • Nedergaard, M. (1988) Mechanisms of brain damage in focal cerebral ischemia. Acta. Neurologica. Scandinavica. 77, 1–24.

    Google Scholar 

  • Nedergaard, M., and Hansen, A. J. (1993) Characterization of cortical depolarizations evoked in focal cerebral ischemia. J. Cereb. Blood Flow Metab. 13, 568–74.

    PubMed  CAS  Google Scholar 

  • Nedergaard, M., Jakobsen, J., and Diemer, N. H. (1988) Autoradiographic determination of cerebral glucose content, blood flow, and glucose utilization in focal ischemia of the rat brain: influence of the plasma glucose concentration. J. Cereb. Blood Flow Metab. 8, 100–108.

    PubMed  CAS  Google Scholar 

  • Nicholson, C., Bruggencate, G. T., Steinberg, R., and Stockle, H. (1977) Calcium modulation in brain extracellular microenvironment demonstrated with ion-selective micropipette. Proc. Natl. Acad. Sci. USA 74, 1287–1290.

    PubMed  CAS  Google Scholar 

  • Nogawa, S., Zhang, F., Ross, E., and Iadecola, C. (1997) Cyclooxygenase-2 gene expression in neurons contributes to ischemic brain damage. J. Neurosci. 17, 2746–2755.

    PubMed  CAS  Google Scholar 

  • Nordstrom, C. H., and Siesjo, B. K. (1978) Effects of phenobarbital in cerebral ischemia. Part I: cerebral energy metabolism during pronounced incomplete ischemia. Stroke 9, 327–335.

    PubMed  CAS  Google Scholar 

  • Nowak, T. S., and Jacewicz, M. (1994) The heat shock/stress response in focal cerebral ischemia. Brain Pathol. 4, 67–76.

    PubMed  Google Scholar 

  • Olney, J. W. (1969) Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate. Science 164, 719–721.

    PubMed  CAS  Google Scholar 

  • Onodera, H., Sato, G., and Kogure, K. (1986) Lesions to Schaffer collaterals prevent ischemic death of CA1 pyramidal cells. Neurosci. Lett. 68, 169–174.

    PubMed  CAS  Google Scholar 

  • Rehncrona, S., Folbergrova, J., Smith, D. S., and Siesjo, B. K. (1980) Influence of complete and pronounced incomplete cerebral ischemia and subsequent recirculation on cortical concentrations of oxidized and reduced glutathione in the rat. J. Neurochem. 34, 477–486.

    PubMed  CAS  Google Scholar 

  • Rehncrona, S., Hauge, H. N., and Siesjo, B. K. (1989) Enhancement of iron-catalyzed free radical formation by acidosis in brain homogenates: differences in effect by lactic acid and CO2. J. Cereb. Blood Flow Metab. 9, 65–70.

    PubMed  CAS  Google Scholar 

  • Ren, J. M., and Finklestein, S. P. (1997) Trophic factor treatment for stroke. in: Primer on Cerebrovascular Diseases (Welsh M., Caplan L., Siesjo B., Weir B. and Reis, D. J., eds.), Academic, San Diego, CA, pp. 34–37.

    Google Scholar 

  • Rothman, S. (1984) Synaptic release of excitatory amino acid neurotransmitter mediates anoxic neuronal death. J. Neurosci. 4, 1884–1891.

    PubMed  CAS  Google Scholar 

  • Rothman, S. M. (1983) Synaptic activity mediates death of hypoxic neurons. Science 220, 536–537.

    PubMed  CAS  Google Scholar 

  • Salgado, A. V., Jones, S. C., FurIan, A. J., Korfali, E., Marshall, S. A., and Little, J. R. (1989) Bimodal treatment with nimodipine and low-molecular-weight dextran for focal cerebral ischemia in the rat. Ann. Neurol. 26, 621–627.

    PubMed  CAS  Google Scholar 

  • Samdeni, A. F., Dawson, T. M., and Dawson, V. L. (1997) Nitric oxide synthase in models of focal ischemia. Stroke 28, 1283–1288.

    Google Scholar 

  • Schanne, F. A., Kane, A. B., Young, E. E., and Farber, J. L. (1979) Calcium dependence of toxic cell death: a final common pathway. Science 206, 700–702.

    Google Scholar 

  • Sharp, F. R., and Sagar, S. M. (1994) Alterations in gene expression as an index of neuronal injury: heat shock and the immediate early gene response. Neurotoxicology 15, 51–59.

    PubMed  CAS  Google Scholar 

  • Siesjo, B. K., and Bengtsson, F. (1989) Calcium fluxes, calcium antagonists, and calcium-related pathology in brain ischemia, hypoglycemia, and spreading depression: a unifying hypothesis. J. Cereb. Blood Flow Metab. 9, 127–140.

    PubMed  CAS  Google Scholar 

  • Silver, I. A., and Erecinska, M. (1990) Intracellular and extracellular changes of [Ca2+] in hypoxia and ischemia in rat brain in vivo. J. Gen. Physiol. 95, 837–866.

    PubMed  CAS  Google Scholar 

  • Simon, R. P., Swan, J. H., Griffiths, T., and Meldrum, B. S. (1984) Blockade of Nmethyl-D-aspartate receptors may protect against ischemic damage in the brain. Science 226, 850–852.

    Google Scholar 

  • Stanimirovic, D. B., Ball, R., and Durkin, J. P. (1997) Stimulation of glutamate uptake and Na,K-ATPase activity in rat astrocytes exposed to ischemia-like insults. Glia 19, 123–134.

    Google Scholar 

  • Steen, P. A., Newberg, L. A., Milde, J. H., and Michenfelder, J. D. (1983) Nimodipine improves cerebral blood flow and neurologic recovery after complete cerebral ischemia in the dog. J. Cereb. Blood Flow Metab. 3, 38–43.

    PubMed  CAS  Google Scholar 

  • Stephenson, D. T., Rash, K., and Clemens, J. A. (1992) Amyloid precursor protein accumulates in regions of neurodegeneration following focal cerebral ischemia in the rat. Brain Res. 593, 128–135.

    PubMed  CAS  Google Scholar 

  • Stroemer, R. P., and Rothwell, N. J. (1997) Cortical protection by localized striatal injection of IL- lra following cerebral ischemia in the rat. J. Cereb. Blood Flow Metab. 17, 597–604.

    Google Scholar 

  • Symon, L., Pasztor, E., and Branston, N. M. (1974) The distribution and density of reduced cerebral blood flow following acute middle cerebral artery occlusion: an experimental study by the technique of hydrogen clearance in baboons. Stroke 5, 355–364.

    PubMed  CAS  Google Scholar 

  • Tagaya, M., Liu, K. F., Copeland, B., Seiffert, D., Engler, R., Garcia, J. H., and del Zoppo, G. J. (1997) DNA scission after focal brain ischemia. Temporal differences in two species. Stroke 28, 1245–1254.

    Google Scholar 

  • Tamura, A., Graham, D. I., McCulloch, J., and Teasdale, G. M. (1981) Focal cerebral ischaemia in the rat: 2. Regional cerebral blood flow determined by [14C]iodoantipyrine autoradiography following middle cerebral artery occlusion. J. Cereb. Blood Flow Metab. 1, 61–69.

    Google Scholar 

  • Tominaga, T., Kure, S., Narisawa, K., and Yoshimoto, T. (1993) Endonuclease activation following focal ischemic injury in the rat brain. Brain Res. 608, 21–26.

    PubMed  CAS  Google Scholar 

  • Touzani, O., Young, A. R., Derlon, J. M., Beadouin, V., Marchal, G., Rioux, P., Mezenge, F., Baron, J. C., and MacKenzie, E. T. (1995) Sequential studies of severely hypometabolic tissue volumes after permanent middle cerebral occlusion: a positron emission tomographic investigation in anesthetized baboons. Stroke 26, 2112–2119.

    PubMed  CAS  Google Scholar 

  • Traystman, R. J., Kirsch, J. R., and Koehler, R. C. (1991) Oxygen radical mechanisms of brain injury following ischemia and reperfusion. J. Appl. Physiol. 71, 1185–1195.

    PubMed  CAS  Google Scholar 

  • Tymianski, M., Wallace, M. C., Spigelman, I., Uno, M., Carlen, P. L., Tator, C. H., and Charlton, M. P. (1993) Cell-peeant Ca2+ chelators reduce early excitotoxic and ischemic neuronal injury in vitro and in vivo. Neuron 11, 221–235.

    PubMed  CAS  Google Scholar 

  • Uematsu, D., Araki, N., Greenberg, J. H., Sladky, J., and Reivich, M. (1991) Combined therapy with MK-801 and nimodipine for protection of ischemic brain damage. Neurology 41, 88–94.

    PubMed  CAS  Google Scholar 

  • Uemura, Y., Kowall, N. W., and Moskowitz, M. A. (1991) Focal ischemia in rats causes time-dependent expression of c-fos protein immunoreactivity in widespread regions of ipsilateral cortex. Bra in Res. 552, 99–105.

    CAS  Google Scholar 

  • Vibulsreth, S., Hefti, F., Ginsberg, M. D., Dietrich, W. D., and Busto, R. (1987) Astrocytes protect cultured neurons from degeneration induced by anoxia. Brain Res. 422, 303–311.

    PubMed  CAS  Google Scholar 

  • Walker, B. D., Smith, P., Curtis, S., Unwin, H., and Greenlee, R. (1995) Amphetamine paired with physical therapy accelerates motor recovery after stroke. Further evidence. Stroke 26, 2254–2259.

    Google Scholar 

  • Warach, S., Gaa, J., Siewert, B., Wielopolski, P., and Edelman, R. R. (1995) Acute human stroke studied by whole brain echo planar diffusion-weighted magnetic resonance imaging. Ann. Neurol. 37, 231–241.

    PubMed  CAS  Google Scholar 

  • Welch, K. M. A., Windham, J., Knight, R. A., Nagesh, V., Hugg J. W., Jacobs, M., Peck, D., Booker, P., Deresky, M. O., and Levine, S. R. (1995) A model to predict the histopathology of human stroke using diffusion and T2-weighted magnetic resonance imaging. Stroke 26, 1983–1989.

    PubMed  CAS  Google Scholar 

  • Yoshida, S., Abe, K., Busto, R., Watson, B. D., Kogure, K., and Ginsberg, M. D. (1982) Influence of transient ischemia on lipid-soluble antioxidants, free fatty acids and energy metabolites in rat brain. Brain Res. 245, 307–316.

    PubMed  CAS  Google Scholar 

  • Yoshida, T., Limmroth, V., Irikura, K., Moskowitz, M. A. (1994) The NOS inhibitor, 7-nitroindazole, decreases focal infarct volume but not the response to topical acetylcholine in pial vessels. J. Cereb. Blood Flow Metab. 14, 924–929.

    PubMed  CAS  Google Scholar 

  • Yue, T. L., and Feuerstein, G. Z. (1994) Platelet-activating factor: a putative neuromodulator and mediator in the pathophysiology of brain injury. Crit. Rev. Neurobiol. 8, 11–24.

    PubMed  CAS  Google Scholar 

  • Zhang, F., Casey, R., Ross, M. E., and Iadecola, C. (1996a) Aminoguanidine ameliorates and L-arginine worsens brain damage from intraluminal middle cerebral artery occlusion. Stroke 27, 317–323.

    PubMed  CAS  Google Scholar 

  • Zhang, F., Eckman, S., Younkin, S., Hsiao, K. K., and Iadecola, C. (1997) Increased susceptibility to ischemic brain damage in transgenic mice overexpressing the amyloid precursor protein. J. Neurosci. 17, 7655–7661.

    PubMed  CAS  Google Scholar 

  • Zhang, F., and Iadecola, C. (1994) Reduction of focal cerebral ischemic damage by delayed treatment with nitric oxide donors. J. Cereb. Blood Flow Metab. 14, 574–580.

    PubMed  CAS  Google Scholar 

  • Zhang, F, White, J. G., and Iadecola, C. (1994a) Nitric oxide donors increase blood flow and reduce brain damage in focal ischemia: evidence that nitric oxide is beneficial in the early stages of cerebral ischemia. J. Cereb. Blood Flow Metab. 14, 217–226.

    PubMed  CAS  Google Scholar 

  • Zhang, R. L., Chopp, M., Chen, H., and Garcia, J. H. (1994b) Temporal profiile of ischemic tissue damage, neutrophil response, and vascular plugging following perma nent and transient (2H) middle cerebral artery occlusion in the rat. J. Neurol. Sci. 125, 3–10.

    Google Scholar 

  • Zhang, R. L., Chopp, M., Li, Y., Zaloga, C., Jiang, N., Jones, M. L., Miyasaka, M., and Ward, P. A. (1994c) Anti-ICAM-1 antibody reduces ischemic cell damage after transient middle cerebral artery occlusion in the rat. Neurology 44, 1747–1751.

    Google Scholar 

  • Zhang, Z. G., Reif, D., Macdonald, J., Tang, W. X., Kamp, D., Gentile, R., Shakespeare, W., Murray, R., and Chopp, M. (1996b) ARL 17477, a potent and selective neuronal NOS inhibitor decreases infarct volume after transient middle cerebral artery occlusion in rats.J. Cereb. Blood Flow Metab. 16, 599–604.

    Google Scholar 

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  1. Costantino Iadecola
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  1. Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada

    Wolfgang Walz

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Iadecola, C. (1999). Mechanisms of Cerebral Ischemic Damage. In: Walz, W. (eds) Cerebral Ischemia. Contemporary Neuroscience. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-479-5_1

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