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Original Article
Year : 2018   |  Volume : 10  |  Issue : 3  |  Page : 132-140

Possible mechanism of sustained 5-adenosine monophosphate-activated protein kinase activator associated with neuronal nitric oxide synthase inhibition in global cerebral ischemia-induced neurodegeneration in rats

Global cerebral ischemia (GCI) is a clinical condition that causes a deprivation of blood supply and energy in the brain due to blockade of carotid arteries. The decreased level of oxygen and glucose causes various cellular changes leading to excitotoxicity and oxidative damage. Cerebral ischemia leads to cell death in CA1 region of the hippocampus, which occurs 3–4 days after an initial ischemic insult and neurodegeneration is evident by 3 days of reperfusion, and neuronal death culminates by 6 days. GCI was induced by bilateral carotid artery occlusion for 10 min. 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) (50 μg and 100 μg) and 3-Br-7-nitroindazole (10 μg, 20 μg, and 50 μg) were administered once a daily for 4 days as a treatment. Cerebral ischemia leads to 5-adenosine monophosphate-activated protein kinase (AMPK) activation, and further administration of AICAR leads to sustained activation of AMPK. Literature has suggested that AMPK activation causes stimulation of mitochondrial biogenesis resulting in an increase in free radical accumulation. In the present study, cerebral ischemia has been noted to cause: Increased malondialdehyde levels, decreased glutathione levels, increased lactate dehydrogenase levels, and decreased acetylcholinesterase levels, and increased nitrate levels in brain homogenate. AMPK activation through AICAR administration was observed to damage cortex and hippocampal regions of brain as are evident from photomicrographs. Thus, it may be concluded from the present study that AMPK activation in ischemic animals leads to neurodegeneration.
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