Cerebral ischemia initiates a cascade of detrimental events including glutamate associated excitotoxicity, membrane lipid degradation, DNA damage, formation of reactive oxygen species andacute inflammation, which lead to the disruption of cellular homeostasis and structural damage of ischemic brain tissue. Inflammation is increasingly recognized to be the key element in pathological progression of ischemic stroke. Therefore, reducing oxidative stress and downregulating the inflammatory response are options that merit consideration as potential therapeutic targets for ischemic stroke. Consequently, agents capable of modulating both elements will constitute promising therapeutic solutions but as of now no such therapies have been translated to clinical application. Hence we hypothesized that contribution of oxidative and inflammatory response through TNF receptors in the course of ischemic cell death and its modulation by natural herbs may be of prime significance.Natural agent Gingko biloba extract (GBE) has been previously reported to be useful in the treatment of various cardiovascular diseases and neuronal degeneration. Here in this study we used an in vitro murine model of ischemia (PC-12 cells exposed to oxygen–glucose deprivation[OGD]/reperfusion) andinvestigated the effects of this natural agentin neuroprotection and cell survival after ischemic injury.We observed that the treatment of cultures with GBE significantly increased cell viability and decreased NO generation in a dose-dependent manner. GBE (50 and 100 μg/ml) treatment of OGD exposed cellsmarkedly reduced the injury associated with increases in inducible nitric oxide synthase (iNOS), and active caspase-3 protein expressions as well as the mRNA expression of TNF-a. This effect may be partiallymediated by the inhibition of TNF-α activation, followed by the inhibition of inflammatory responses in PC12 cells. Therefore, GBE treatment may represent a novel approach for lowering the risk of or improving function in ischemia-reperfusion brain injury-related disorders.
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