title: Inhibitory effects of p38 inhibitor against mitochondrial dysfunction in the early brain injury after subarachnoid hemorrhage in mice.
abstract: 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.
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, China.
authors.forename: Liyong
authors.initials: L
authors.lastname: Huang
authors.forename: Jia
authors.initials: J
authors.lastname: Wan
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Hui
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Dawei
authors.initials: D
authors.lastname: Xu
authors.forename: Wenke
authors.initials: W
authors.lastname: Zhou
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001930:Brain Injuries / Q000150:complications* / Q000188:drug therapy / Q000209:etiology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use; D020287:In Situ Nick-End Labeling; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D051379:Mice; D028361:Mitochondrial Diseases / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D013345:Subarachnoid Hemorrhage / Q000150:complications*; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580