NEUROTHERAPEUTIC EVALUATION OF KOLAVIRON IN A 2-VESSEL OCCLUSION MODEL OF GLOBAL CEREBRAL ISCHEMIA/REPERFUSION-MEDIATED BRAIN INJURY

Abstract

Brain damage as a consequence of cardiac arrest and stroke is a leading cause of death and long-term disability worldwide with overwhelming majority of strokes adduced to cerebral ischemia. Kolaviron, the predominant bioactive constituent in Garcinia kola seeds have been reported to demonstrate prophylactic efficacy against cerebral ischemia/reperfusion injury. In this study, the effects of post-treatment with Kolaviron in rats with cerebral ischemia/reperfusion injury have been investigated in order to ascertain its efficacy as a potential therapeutic agent for stroke. Male Wistar rats were subjected to 30 min of bilateral common carotid artery occlusion (BCCAO) followed by 24 h of reperfusion (BCCAO/R) and then administered 25 mg/kg kolaviron, 50 mg/kg kolaviron, 100 mg/kg kolaviron or 20 mg/kg quercetin (i.p.). Animals were assessed and scored for motor and cognitive deficits 24 h after reperfusion and then euthanized for dissection of cortices, striata and hippocampi which were processed for biochemical estimations. The effect of kolaviron on BCCAO/R-induced oxidative stress was estimated by assaying for catalase, xanthine oxidase, glutathione peroxidase and superoxide dismutase (SOD) activities as well as malondiadehyde (MDA) and glutathione (GSH) levels. The effect of kolaviron on BCCAO/R-induced inflammation was assessed by evaluating the relative brain weight and water content as well as nitrite level and myeloperoxidase activity. The influence of kolaviron on dopamine metabolism was assessed by evaluating the activities of tyrosine hydroxylase and monoamine oxidase as well as determining dopamine concentration while the modulation of BCCAO/R-evoked excitotoxicity was assessed by assaying for glutamine synthetase, lactate dehydrogenase, Na+ K+ ATPase and acetylcholine esterase activities. In addition, hippocampal mitochondrial integrity was assessed as well as histopathological examination of the hippocampal CA1, CA2, and CA3 regions. Results indicated that there was significant (p<0.01) reversal of motor and cognitive deficits in ischemic rats treated with kolaviron as Brain damage as a consequence of cardiac arrest and stroke is a leading cause of death and long-term disability worldwide with overwhelming majority of strokes adduced to cerebral ischemia. Kolaviron, the predominant bioactive constituent in Garcinia kola seeds have been reported to demonstrate prophylactic efficacy against cerebral ischemia/reperfusion injury. In this study, the effects of post-treatment with Kolaviron in rats with cerebral ischemia/reperfusion injury have been investigated in order to ascertain its efficacy as a potential therapeutic agent for stroke. Male Wistar rats were subjected to 30 min of bilateral common carotid artery occlusion (BCCAO) followed by 24 h of reperfusion (BCCAO/R) and then administered 25 mg/kg kolaviron, 50 mg/kg kolaviron, 100 mg/kg kolaviron or 20 mg/kg quercetin (i.p.). Animals were assessed and scored for motor and cognitive deficits 24 h after reperfusion and then euthanized for dissection of cortices, striata and hippocampi which were processed for biochemical estimations. The effect of kolaviron on BCCAO/R-induced oxidative stress was estimated by assaying for catalase, xanthine oxidase, glutathione peroxidase and superoxide dismutase (SOD) activities as well as malondiadehyde (MDA) and glutathione (GSH) levels. The effect of kolaviron on BCCAO/R-induced inflammation was assessed by evaluating the relative brain weight and water content as well as nitrite level and myeloperoxidase activity. The influence of kolaviron on dopamine metabolism was assessed by evaluating the activities of tyrosine hydroxylase and monoamine oxidase as well as determining dopamine concentration while the modulation of BCCAO/R-evoked excitotoxicity was assessed by assaying for glutamine synthetase, lactate dehydrogenase, Na+ K+ ATPase and acetylcholine esterase activities. In addition, hippocampal mitochondrial integrity was assessed as well as histopathological examination of the hippocampal CA1, CA2, and CA3 regions. Results indicated that there was significant (p<0.01) reversal of motor and cognitive deficits in ischemic rats treated with kolaviron as