| Background: Cerebrovascular disease is the third leading cause of death in the world. Ischemic cerebrovascular disease is the most common type in the cerebrovascular disease. Cerebral ischemia/reperfusion injury is a complex pathophysiologic process which is not been clarified now. Recent studies found that the injuries caused by cerebral blood flow cessation and reperfusion are a rapid cascade reaction which includes disfunction of ATP production, overproduction of reactive oxygen species, intracellular acidosis , increased release of excitatory amion acids, destabilization of intracellular calcium and apoptosis-related genes activation and so on. These pathophysiologic processes overlap and intercommunicate then form a vicious cycle which results in cell apoptosis or necrosis. It is a focus in neuroscience that looking for the ideal neuroprotective agents that can block ischemic cascade reaction. Curcumin is a phenol derived from tumeric which has anticancer, antiinflammation, anti-HIV and antioxidation properties and low toxic and side-effect. It has good potential in clinic. From recent years, curcumin was been found that it has understanding application prospect in neuroprotction and therapeutics of cerebrovascular disease because of its antioxidation and antiinflammation properties.Objecitve: To study neuroprotective effects of curcumin on focal cerebral ischemia/reperfusion injury in rats and explore its possible mechanisms and related signal transduction pathways.Methods: Part one : Transient cerebral ischemia/reperfusion model in rats was established by middle cerebral artery occlusion using modified suture occlusion technique.The rats were randomly divided into sham group, MCAO group, curcumin-treated group. Neuroscores of all groups were evaluated. Infarct volume was measured by TTC staining and morphologic changes were observed by H.E. and Nissl staining. TUNEL was used for detecting cell apoptosis. Meanwhile, we measured Malondialdehyde (MDA) and superoxide dismutase(SOD) of cerebral tissue to evaluate antioxidation activitis of curcumin . Part two: TTC staining, immunohistochemisty , Western blot technique were used to explore neuroprotection of curcumin on focal cerebral ischemia/reperfusion injury in rats ,with or without the existence of LY294002(a inhibitor of phosphatidylinositol-3- kinase ,PI3K).And also, the effects of curcumin on the expression of phospha-Akt, apoptosis-associated protein Bcl2/Bax,Caspase3 ,transcript factor Nrf2 and NQO1. Results: Part one: Curcumin could significantly improve the neurologic impairment, reduce cerebral infarct volume and decrease neuronal apoptosis and necrosis. And also, curcumin could decrease the level of MDA whereas increase the level of SOD. Part two: Curcumin could increase the expression of pAkt, antiapoptosis protein Bcl-2, transcript factor Nrf2 and II detoxifying enzymes NQO1 whereas decrease the expression of proapoptosis protein Bax and caspase-3. However, with the existence of LY294002, the neuroprotection of curcumin was inhibited. Improvement of neurologic impairment and reduction of cerebral infarct volume in Cur+LY group were less than that in CUR group. Moreover, the expression of pAkt, Bcl-2/Bax , Nrf2 and NQO1 in CUR+LY group were lower than that in CUR group whereas the expression of caspase-3 protein in CUR+LY group was higher than that in CUR group.Conclusions: 1.Curcumin has exact neuroprotective effects on focal cerebral ischemia/reperfusion injuries on rats which could inhibit the neuronal apoptosis and necrosis, reduce cerebral infarct volume and improve neurologic impairment. 2. The neuroprotection of curcumin was accomplished by antioxidation and antiapoptosis. It was one of important neuroprotective mechanisms of curcumin that regulating the expression of apoptosis-associated protein and antioxidative enzyme by PI3K/Akt pathway.
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