Pharmacological investigation sonneuro inflammatory and excite toxic mechanisms in animal model of stroke

Abstract

Stroke is a devastating clinical condition and millions of people die every year due to stroke making it the world s second leading cause of death and a third major cause of disability. Post-stroke pathological cascades exaggerate the primary injury and lead to secondary neuronal damage. The present thesis work has been designed to investigate the involvement and pharmacological management of neuroinflammation and excitotoxicity in the pathological progression of stroke-induced cerebral injury. Ischemic stroke was induced in rats by either the bilateral common carotid artery occlusion model or by the middle cerebral artery occlusion model. For in vitro studies, the oxygen-glucose deprivation model was used to induce ischemia whereas hemorrhagic stroke was induced by intrastriatal injections of collagenase. Various pharmacological interventions were investigated such as licofelone, azilsartan, coenzyme Q10, azelnidipine, citicoline, acamprosate and minocycline and diverse pharmacological assessments were performed such as behavioural function, oxidative stress parameters, neuroinflammatory mediators and gene/protein expression, immunohistochemistry (glial parameters), excitotoxicity, mitochondrial polarography and histological assessments. Licofelone showed potent anti-inflammatory action against both ischemic and hemorrhagic stroke, azilsartan improved mitochondrial function whereas acamprosate and azelnidipine reduced excitotoxic damage. To conclude, the research work in this study highlights the pharmacological utility of newlinevarious new drug interventions or combinations of existing drugs against experimentally induced ischemic or hemorrhagic stroke. The study comprehensively unfolds the entangled pathological mechanisms involved in the neuroprotective effect of these drugs and provides hope that such pharmacological interventions can be further researched and used in the treatment of these devastating clinical conditions. newline newline