Inhibitory effects of p38 inhibitor against mitochondrial dysfunction in the early brain injury after subarachnoid hemorrhage in mice
2013
Huang, Liyong | Wan, Jia | Chen, Ying | Wang, Zhongwei | Hui, Lei | Li, Yan | Xu, Dawei | Zhou, Wenke
Brain injury occurred in the early stage after subarachnoid hemorrhage (SAH) can activate p38 mitogen-activated protein kinase (MAPK), which, in turn, not only regulates mitochondrial structure and function, but also triggers cell death though mitochondrial pathway. Although a lot of work has been done, the relationship between p38 and mitochondrial dysfunction has not been delineated in the early brain injury after SAH. The purpose of this study was to do such an exploration. SAH mouse model was established using single-hemorrhage method. We performed immunohistochemical and enzyme activity analysis, respectively, to detect the alteration of p-p38, cytorosome c (cyt c), mitochondrial membrane potential, ATP content, and lactate dehydrogenase (LDH) activation, as well as TUNEL assay to detect cell apoptosis at the different time course of SAH. p-p38 expression after SAH was significantly higher than that of in SB203580 treated counterparts. As for mitochondrial dysfunction events, mitochondrial membrane potential was significantly decreased with the time course of SAH, whereas it was returned to normal level and maintained at a stable level after treatment with SB203580. Meanwhile, after SAH the decreased ATP content, and increased cyt c and LDH level were all returned to normal level in SB203580 treated group. In addition, SB203580 significantly inhibited apoptosis. These results demonstrated that the neuroprotective effects of p38 inhibitor may be rely on the prevention of mitochondrial dysfunction, therefore blocking neuronal cell death, emphasizing on the importance of early therapeutic intervention by targeting p38, and suggesting a potential therapeutic window before greater cortex dysfunction occurs.
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