Use of a poly(ADP-ribose) polymerase inhibitor to suppress inflammation and neuronal death after cerebral ischemia-reperfusion
Use of a poly(ADP-ribose) polymerase inhibitor to suppress inflammation and neuronal death after cerebral ischemia-reperfusion
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DOI：
10.1161/01.str.0000250742.61241.79
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发表时间：
2007-02-01
期刊：
影响因子：
8.3
通讯作者：
Swanson, Raymond A.
中科院分区：
文献类型：
--
作者：
Hamby, Aaron M.;Suh, Sang Won;Swanson, Raymond A.
背景和目的：大多数脑卒中患者在发生脑缺血数小时后才就诊。因此，神经保护策略需要相对较长的治疗窗口。聚（adp -核糖）聚合酶抑制剂如PJ34已知可抑制小胶质细胞活化，这是一种可能导致神经元死亡的缺血后事件。我们评估了短暂性前脑缺血8小时后给予PJ34的效果。方法：大鼠前脑缺血10分钟，再灌注后8小时开始用PJ34治疗7 d。在缺血后0 ~ 14天的连续时间点用CD11b免疫染色法检测活化的小胶质细胞和浸润的巨噬细胞。观察缺血后7天CA1神经元的存活情况。结果：PJ34治疗的大鼠显示小胶质细胞/巨噬细胞活化几乎完全抑制（第5天评估），CA1神经元死亡减少84%。结论：短暂性缺血再灌注后8小时给予PJ34对CA1存活有较大的保护作用。这种作用可能是通过抑制脑缺血后炎症反应介导的。（中风。2007;38[part 2]:632-636。）
Background and Purpose-Most stroke patients do not present for medical treatment until several hours after onset of brain ischemia. Consequently, neuroprotective strategies are required with comparably long therapeutic windows. Poly(ADP-ribose) polymerase inhibitors such as PJ34 are known to suppress microglial activation, a postischemic event that may contribute to neuronal death. We evaluated the effects of PJ34 administered 8 hours after transient forebrain ischemia. Methods-Rats were subjected to 10 minutes of forebrain ischemia and treated with PJ34 for 7 days beginning 8 hours after reperfusion. Activated microglia and infiltrating macrophages were evaluated at serial time points between zero and 14 days after ischemia by immunostaining for CD11b. CA1 neuronal survival was evaluated 7 days after ischemia. Results-Rats treated with PJ34 showed a near-complete inhibition of microglia/macrophage activation (evaluated on day 5) and an 84% reduction in CA1 neuronal death. Conclusions-Administration of PJ34 as late as 8 hours after transient ischemia-reperfusion has a large protective effect on CA1 survival. This effect may be mediated by suppression of the postischemic brain inflammatory response. (Stroke. 2007;38[part 2]:632-636.)