Increased p38 mitogen-activated protein kinase signaling is involved in the oxidative stress associated with oxygen and glucose deprivation in neonatal hippocampal slice cultures

被引:44
作者
Lu, Qing [1 ]
Rau, Thomas F. [2 ]
Harris, Valerie [1 ]
Johnson, Maribeth [3 ]
Poulsen, David J. [2 ]
Black, Stephen M. [1 ]
机构
[1] Med Coll Georgia, Vasc Biol Ctr, Augusta, GA 30912 USA
[2] Univ Montana, Dept Biomed & Pharmaceut Sci, Missoula, MT 59812 USA
[3] Georgia Hlth Sci Ctr, Dept Biostat, Augusta, GA USA
关键词
apoptosis; hypoxia-ischemia; neonate brain; neuronal cell death; rat; superoxide; MAP KINASE; CELL-DEATH; PROVIDES NEUROPROTECTION; CASPASE-3; ACTIVATION; PHOSPHORYLATION; INHIBITOR; HYPOXIA; NEURONS; STROKE; MODEL;
D O I
10.1111/j.1460-9568.2011.07786.x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The pathological basis of neonatal hypoxia-ischemia (HI) brain damage is characterized by neuronal cell loss. Oxidative stress is thought to be one of the main causes of HI-induced neuronal cell death. The p38 mitogen-activated protein kinase (MAPK) is activated under conditions of cell stress. However, its pathogenic role in regulating the oxidative stress associated with HI injury in the brain is not well understood. Thus, this study was conducted to examine the role of p38 MAPK signaling in neonatal HI brain injury using neonatal rat hippocampal slice cultures exposed to oxygen / glucose deprivation (OGD). Our results indicate that OGD led to a transient increase in p38 MAPK activation that preceded increases in superoxide generation and neuronal death. This increase in neuronal cell death correlated with an increase in the activation of caspase-3 and the appearance of apoptotic neuronal cells. Pre-treatment of slice cultures with the p38 MAPK inhibitor, SB203580, or the expression of an antisense p38 MAPK construct only in neuronal cells, through a Synapsin I-1-driven adeno-associated virus vector, inhibited p38 MAPK activity and exerted a neuroprotective effect as demonstrated by decreases in OGD-mediated oxidative stress, caspase activation and neuronal cell death. Thus, we conclude that the activation of p38 MAPK in neuronal cells plays a key role in the oxidative stress and neuronal cell death associated with OGD.
引用
收藏
页码:1093 / 1101
页数:9
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