Reactive oxygen intermediates contribute to necrotic and apoptotic neuronal injury in an infant rat model of bacterial meningitis due to group B streptococci
Reactive oxygen intermediates contribute to necrotic and apoptotic neuronal injury in an infant rat model of bacterial meningitis due to group B streptococci
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DOI：
10.1172/jci119084
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发表时间：
1996-12-01
影响因子：
15.9
通讯作者：
Tauber, MG
中科院分区：
文献类型：
--
作者：
Leib, SL;Kim, YS;Tauber, MG
活性氧中间体(ROI)参与脑缺血和创伤后神经元的损伤。在这项研究中，我们探讨了ROI在细菌性脑膜炎中的作用。由B群链球菌引起的幼年大鼠脑膜炎导致两种不同形式的神经元损伤，皮质坏死区和海马齿状回神经元丢失，后者显示出细胞凋亡的证据。脑组织切片经锰缓冲液灌流后的二氨基联胺染色和脑组织匀浆中脂质过氧化产物的测定都提供了脑膜炎导致ROI产生的证据。用自由基清除剂α-苯基叔丁基硝酮(PEN)(100 mg/kg，q8h，i.p.)治疗。从感染时开始，完全取消了ROI检测和脂质过氧化增加。脑膜炎动物的大脑皮质灌注量减少到非感染对照组的37.5+/-21.0%(P<；0.05)，PEN恢复到对照组的72.0+/-8.1%(P<；0.05比脑膜炎)。PEN在感染时启动时也完全防止了皮层和海马区的神经元损伤(P<；0.02)，并在感染18小时后与抗生素一起启动时显著减少了这两种形式的损伤(皮层P<；0.004和海马区P<；0.001)。这些数据表明，在这种新生儿脑膜炎模型中，ROI的产生是导致脑缺血和坏死性和凋亡性神经元损伤的主要原因。
Reactive oxygen intermediates (ROI) contribute to neuronal injury in cerebral ischemia and trauma. In this study we explored the role of ROI in bacterial meningitis. Meningitis caused by group B streptococci in infant rats led to two distinct forms of neuronal injury, areas of necrosis in the cortex and neuronal loss in the dentate gyrus of the hippocampus, the latter showing evidence for apoptosis. Staining of brain sections with diaminobenzidine after perfusion with manganese buffer and measurement of lipid peroxidation products in brain homogenates both provided evidence that meningitis led to the generation of ROI. Treatment with the radical scavenger alpha-phenyl-tert-butyl nitrone (PEN) (100 mg/kg q8h i.p.) beginning at the time of infection completely abolished ROI detection and the increase in lipidperoxidation. Cerebral cortical perfusion was reduced in animals with meningitis to 37.5 +/- 21.0% of uninfected controls (P < 0.05), and PEN restored cortical perfusion to 72.0 +/- 8.1% of controls (P < 0.05 vs meningitis). PEN also completely prevented neuronal injury in the cortex and hippocampus, when started at the time of infection (P < 0.02), and significantly reduced both forms of injury, when started 18 h after infection together with antibiotics (P < 0.004 for cortex and P < 0.001 for hippocampus). These data indicate that the generation of ROI is a major contributor to cerebral ischemia and necrotic and apoptotic neuronal injury in this model of neonatal meningitis.