Amelioration of hippocampal neuronal damage after transient forebrain ischemia in cyclooxygenase-2-deficient mice
Amelioration of hippocampal neuronal damage after transient forebrain ischemia in cyclooxygenase-2-deficient mice
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DOI：
10.1097/01.wcb.0000100065.36077.4a
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发表时间：
2004-01-01
影响因子：
6.3
通讯作者：
Hori, M
中科院分区：
文献类型：
--
作者：
Sasaki, T;Kitagawa, K;Hori, M
一些研究表明，环氧合酶-2（考克斯-2）在缺血性神经元死亡中起作用。考克斯-2的遗传破坏已被证明可降低对局灶性缺血损伤和N-甲基-D-天冬氨酸介导的神经毒性的易感性。本研究的目的是检测考克斯-2缺陷对短暂性前脑缺血后神经元易损性的影响。考克斯-2免疫染色在缺血早期即明显上调，缺血后3天以上，考克斯-2染色在CA 1内侧区和CA 2区持续明显。考克斯-2染色的免疫组织学模式在这些部门逐渐浓缩到核周围的位置。考克斯-2缺陷小鼠全脑缺血引起的海马神经元损伤程度低于野生型小鼠，与海马DNA断裂减弱一致。此外，缺血后使用选择性考克斯-2抑制剂尼美舒利治疗可减少海马神经元损伤。这些环氧化酶-2的遗传破坏和化学抑制的结果表明，抑制考克斯-2可改善小鼠短暂前脑缺血后的选择性神经元死亡。
Several studies have suggested that cyclooxygenase-2 (COX-2) plays a role in ischemic neuronal death. Genetic disruption of COX-2 has been shown to reduce susceptibility to focal ischemic injury and N-methyl-D-aspartate-mediated neurotoxicity. The purpose of this study was to examine the effects of COX-2 deficiency on neuronal vulnerability after transient forebrain ischemia. Marked upregulation of COX-2 immuno-staining in neurons was observed at the early stage and prominent COX-2 staining persisted in the CA1 medial sector and CA2 sector over 3 days after ischemia. The immunohistologic pattern of COX-2 staining in these sectors gradually condensed to a perinuclear location. The degree of hippocampal neuronal injury produced by global ischemia in COX-2-deficient mice was less than that in wild-type mice, coincident with attenuation of DNA fragmentation in the hippocampus. Also, treatment with a selective COX-2 inhibitor, nimesulide, after ischemia decreased hippocampal neuronal damages. These results of genetic disruption and chemical inhibition of cyclooxygenase-2 show that inhibition of COX-2 ameliorates selective neuronal death after transient forebrain ischemia in mice.