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PHARMASPIRE - Volume 10, Issue 2, April - June, 2018

Pages: 68-86

Date of Publication: 14-Jun-2022

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Neuroprotection of brain permeable Forskolin ameliorates behavioral, biochemical and histopathological alterations in rat model of intracerebral hemorrhage

Author: Rajesh Dudi , Sidharth Mehan

Category: Pharmaceutics


Mitochondrial complexes enzymes’ (I, II, IV, and V) dysfunction increases neuroinflammatory cytokines, oxidative stress, and alterations of brain metabolic enzymes may be key pathological hallmarks of cerebral hemorrhage. Here, the first time in the history of this intracerebral hemorrhage (ICH) animal model, we extensively examined the huge range of behavioral, biochemical, neuropathological, morphological, and histopathological effects of direct adenylyl cyclase activator Forskolin (FSK) in adult rats’ brain tissue homogenate, serum, and urine. Intraventricular injection of autologous blood in rats caused impairment in memory, grip strength posture, and cognitive function. Biochemical analysis of brain homogenate, serum, and urine samples in ICH-treated rats showed an increase in altered mitochondrial complexes activities, inflammatory cytokines, oxidative stress, and lipid biomarkers. Neurohistological alterations of hippocampus, basal ganglia, and cerebral cortex of ICH-treated rats exhibit severe neuronal space, irregular damaged cells, and dense pyknotic nuclei-associated marked focal diffused gliosis. FSK (20, 40, and 60 mg/kg, p.o) once-daily treatment for a period of 22 days significantly improved motor performance and cognitive behavior task. Further, FSK treatment significantly improved mitochondrial complexes’ enzyme activity, attenuated inflammatory, and oxidative damage of rat brain. In present research work, neuroprotective effects of direct AC activator FSK responsible for activation of cyclic adenosine monophosphate/protein kinase further leads to CREB activation, and through the repairing in the basal ganglia, cortex, and hippocampus functioning associate with mitochondrial dysfunctioning in cerebral hemorrhage.

Keywords: Cerebral hemorrhage, neuroinflammation, cyclic adenosine monophosphate, forskolin


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