Abstract
Spontaneous intracerebral hemorrhage (ICH) accounts for 10–15% of all strokes. Despite high incidence, morbidity and mortality, the precise pathophysiology of spontaneous ICH is not fully understood, while there is little data concerning the mechanisms that follow the primary insult of the hematoma formation. The cholinergic system, apart from its colossal importance as a neurotransmission system, seems to also play an important role in brain injury recovery. It has been recently suggested that the brain possesses a cholinergic anti-inflammatory pathway that counteracts the inflammatory responses after ICH, thereby limiting damage to the brain itself. We, herein, report the findings of our study concerning the role of acetylcholinesterase (AChE; a crucial membrane-bound enzyme involved in cholinergic neurotransmission) in a porcine model of spontaneous ICH, with a focus on the first 4 and 24 h following the lesion’s induction, in combination with a study of the effectiveness of the lazaroid antioxidant U-74389G administration. Our study demonstrates the activation of AChE activity following U-74389G administration. The lazaroid U-74389G seems to be an established neuroprotectant and this is the first report of its supporting role in the enhancement of cholinergic response to the induction of ICH.
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References
Carageorgiou H, Tzotzes V, Pantos C, Mourouzis C, Zarros A, Tsakiris S (2004) In vivo and in vitro effects of cadmium on adult rat brain total antioxidant status, acetylcholinesterase, (Na+, K+)-ATPase and Mg2+-ATPase activities: protection by L-cysteine. Basic Clin Pharmacol Toxicol 94:112–118
de Haan P, Kalkman CJ, Vanicky I, Jacobs MJ, Drummond JC (1998) Effect of mild hypothermia and the 21-aminosteroid U-74389G on neurologic and histopathologic outcome after transient spinal cord ischemia in the rabbit. J Neurosurg Anesthesiol 10:86–93
Durmaz R, Ertilav K, Akyüz F, Kanbak G, Bildirici K, Tel E (2003) Lazaroid U-74389G attenuates edema in rat brain subjected to post-ischemic reperfusion injury. J Neurol Sci 215:87–93
Egashira T, Goto H, Takeda H, Takada K, Matsumiya T (1999) Alterations in neurotransmitter, amino acid and free radical related substances in cerebrospinal fluid in patients with cerebrovascular diseases. Nippon Ronen Igakkai Zasshi 36:256–261
El-Demerdash FM (2011) Lipid peroxidation, oxidative stress and acetylcholinesterase in rat brain exposed to organophosphate and pyrethroid insecticides. Food Chem Toxicol 49:1346–1352
Ellman GL, Courtney KD, Andres V Jr, Featherstone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95
Fabian RH, Dewitt DS, Kent TA (1998) The 21-aminosteroid U-74389G reduces cerebral superoxide anion concentration following fluid percussion injury of the brain. J Neurotrauma 15:433–440
Farbiszewski R, Chwiecko M, Ustymowicz J (1994) The 21-aminosteroid U-74389G protects the antioxidant enzymes in the ischemia/reperfusion-induced rat brain damage. Eur J Pharmacol 270:263–265
Félix B, Léger ME, Albe-Fessard D, Marcilloux JC, Rampin O, Laplace JP (1999) Stereotaxic atlas of the pig brain. Brain Res Bull 49:1–137
Gonçalves JF, Fiorenza AM, Spanevello RM, Mazzanti CM, Bochi GV, Antes FG, Stefanello N, Rubin MA, Dressler VL, Morsch VM, Schetinger MR (2010) N-Acetylcysteine prevents memory deficits, the decrease in acetylcholinesterase activity and oxidative stress in rats exposed to cadmium. Chem Biol Interact 186:53–60
Harat M, Kochanowski J (1999) Effect of treatment with 21-aminosteroid U-74389G and glucocorticoid steroid methylprednisolone on somatosensory evoked potentials in rat spinal cord during mild compression. J Neurotrauma 16:187–193
Hijioka M, Matsushita H, Hisatsune A, Isohama Y, Katsuki H (2011) Therapeutic effect of nicotine in a mouse model of intracerebral hemorrhage. J Pharmacol Exp Ther 338:741–749
Katsuki H (2010) Exploring neuroprotective drug therapies for intracerebral hemorrhage. J Pharmacol Sci 114:366–378
Lee ST, Chu K, Jung KH, Kang KM, Kim JH, Bahn JJ, Jeon D, Kim M, Lee SK, Roh JK (2010) Cholinergic anti-inflammatory pathway in intracerebral hemorrhage. Brain Res 1309:164–171
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275
Pari L, Murugavel P (2007) Diallyl tetrasulfide improves cadmium induced alterations of acetylcholinesterase, ATPases and oxidative stress in brain of rats. Toxicology 234:44–50
Rodríguez-Yáñez M, Castellanos M, Freijo MM, López Fernández JC, Martí-Fàbregas J, Nombela F, Simal P, Castillo J; en representación del Comité ad hoc del Grupo de Estudio de Enfermedades Cerebrovasculares de la Sociedad Española de Neurología (2011) Clinical practice guidelines in intracerebral haemorrhage. Neurologia; Epub ahead of print
Schallreuter KU, Elwary SM, Gibbons NC, Rokos H, Wood JM (2004) Activation/deactivation of acetylcholinesterase by H2O2: more evidence for oxidative stress in vitiligo. Biochem Biophys Res Commun 315:502–508
Shadnia S, Dasgar M, Taghikhani S, Mohammadirad A, Khorasani R, Abdollahi M (2007) Protective effects of alpha-tocopherol and N-acetyl-cysteine on diazinon-induced oxidative stress and acetylcholinesterase inhibition in rats. Toxicol Mech Methods 17:109–115
Tsakiris S (2001) Effects of L-phenylalanine on acetylcholinesterase and Na+, K + -ATPase activities in adult and aged rat brain. Mech Ageing Dev 122:491–501
Vlkolinský R, Stolc S, Ross A (1999) Effect of stobadine, U-74389G, trolox and melatonin on resistance of rat hippocampal slices to oxidative stress. Life Sci 65:1969–1971
Wagner KR (2007) Modeling intracerebral hemorrhage: glutamate, nuclear factor-kappa B signaling and cytokines. Stroke 38(2 Suppl):753–758
Wagner KR, Xi G, Hua Y, Kleinholz M, de Courten-Myers GM, Myers RE, Broderick JP, Brott TG (1996) Lobar intracerebral hemorrhage model in pigs: rapid edema development in perihematomal white matter. Stroke 27:490–497
Weiner L, Kreimer D, Roth E, Silman I (1994) Oxidative stress transforms acetylcholinesterase to a molten-globule-like state. Biochem Biophys Res Commun 198:915–922
Wyse AT, Stefanello FM, Chiarani F, Delwing D, Wannmacher CM, Wajner M (2004) Arginine administration decreases cerebral cortex acetylcholinesterase and serum butyrylcholinesterase probably by oxidative stress induction. Neurochem Res 29:385–389
Zhou JF, Zhou YH, Zhang L, Chen HH, Cai D (2003) 3,4-methylenedioxymethamphetamine (MDMA) abuse markedly inhibits acetylcholinesterase activity and induces severe oxidative damage and liperoxidative damage. Biomed Environ Sci 16:53–61
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Alexios Bimpis and Apostolos Papalois are authors with equal contribution to the study.
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Bimpis, A., Papalois, A., Tsakiris, S. et al. Activation of acetylcholinesterase after U-74389G administration in a porcine model of intracerebral hemorrhage. Metab Brain Dis 27, 221–225 (2012). https://doi.org/10.1007/s11011-012-9301-2
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DOI: https://doi.org/10.1007/s11011-012-9301-2