Kim Seung-Woo, Yu Young-Mi, Piao Chun Shu, Kim Jung-Bin, Lee Ja-Kyeong
Department of Anatomy, Inha University School of Medicine, 7-241 Shinheung-dong, Jung-Gu, Inchon, 400-712, South Korea.
Brain Res. 2004 May 8;1007(1-2):188-91. doi: 10.1016/j.brainres.2004.02.009.
The activation of p38 mitogen-activated protein kinase (MAPK) has been implicated in the pathological changes accompanying inflammatory and apoptotic processes of various cell types including neurons. In a kainic acid (KA)-induced mouse seizure model, p38 MAPK is induced in reactive astrocytes in the CA3 region of the hippocampus where severe neuronal loss occurs. Here we report the delayed and protracted activation of p38 MAPK in the CA3 region of the hippocampus of mice treated with KA. In this model, the inhibition of p38 MAPK isoforms by SB203580, a specific inhibitor, attenuated neuronal loss in the CA3 and CA1 regions of the hippocampus, which was accompanied by the suppression of the p38 MAPK activation as well as astrogliosis. Thus, the delayed and sustained induction of p38 MAPK plays a crucial role in the neuronal damage of KA-induced brain seizures.
p38丝裂原活化蛋白激酶（MAPK）的激活与包括神经元在内的各种细胞类型的炎症和凋亡过程所伴随的病理变化有关。在 kainic 酸（KA）诱导的小鼠癫痫模型中，海马体CA3区发生严重神经元损失，p38 MAPK 在该区域的反应性星形胶质细胞中被诱导。在此，我们报告了用KA处理的小鼠海马体CA3区中p38 MAPK的延迟和持久激活。在该模型中，特异性抑制剂SB203580对p38 MAPK亚型的抑制减轻了海马体CA3和CA1区的神经元损失，这伴随着p38 MAPK激活以及星形胶质细胞增生的抑制。因此，p38 MAPK的延迟和持续诱导在KA诱导的脑癫痫的神经元损伤中起关键作用。
