| Many researches have shown that penumbral area is a valuable target of therapy in clinic. The cell death ocurred in penumbral area are is mainly due to apoptosis. Recently, it is found that the neuron apoptosis caused by brain ischemia is associated with signal pathway of endoplasmic reticulum stress (ER stress), which is different from the traditional apoptotic pathway. Caspase-12 has been identified as a molecule which initiates apoptosis selectively in response to ER stress and is not activated by other pathways. Caspase-12 is localized on the ER membrane, but once specifically activated by ER stress, it translocates to the cytoplasm. Based on these background, in this study, we observe endoplasmic reticulum stress induced by brain ischemia and investigate the mechanism of protective effect of Edaravone on brain ischemia.This experiment was divided into two parts, in the first part, we established focal cerebral ischemia model by reforming Longa method in Sprague-Dawley rats, and determine the dynamic alteration of GRp78 expression and activation of caspase12. Also, neurological deficits of rats after ischemia were assessed and scored as described by Longa. Then, in the second part, animal model was treated with edaravone and futher observed the above index. Our results showed that the expression of GRP78 was elevated at 2h, 6h, 12h, 24h and 48h post ischemia, and restored at72h; furthermore, caspase-12 was activated at 24h and 48h after ischemia; edaravone treatment could significantly down-regulate the expression of GRP78 and repress the activation of caspase-12.In summary, ER stress response was activated at the acute stage of cerebral ischemia and the degree of ER stress was time dependence. In addition, ER-associated apoptosis was activated in penumbral area which may be responsible for neuron death caused by acute cerebral ischemia. Furthermore, edaravone was shown to repress ER stress and ER stress-associated apoptosis, which may be another protective mechanism of edaravone. |
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