Rabies virus infection of primary neuronal cultures and adult mice: Failure to demonstrate evidence of excitotoxicity
Rabies virus infection of primary neuronal cultures and adult mice: Failure to demonstrate evidence of excitotoxicity
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DOI：
10.1128/jvi.01272-06
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发表时间：
2006-10-01
影响因子：
5.4
通讯作者：
Jackson, Alan C.
中科院分区：
文献类型：
--
作者：
Weli, Simon C.;Scott, Courtney A.;Jackson, Alan C.
从感染狂犬病病毒CVS株的17日龄小鼠胚胎的大脑皮层和海马区获得的培养显示，锥虫蓝排斥消失，形态上出现凋亡特征，并激活了caspase 3的表达，表明细胞凋亡。N-甲基-D-天冬氨酸(NMDA)拮抗剂氯胺酮(125mU)和MK-801(60mU)对CVS感染神经元无明显的神经保护作用，而半胱氨酸氨基转移酶抑制剂Ac-Asp-Glu-Val天冬氨酸醛(25mU)有明显的神经保护作用。在CVS感染的海马神经元中，谷氨酸刺激的细胞内钙水平的增加减少。给感染CVS的成年小鼠灌胃氯胺酮(120 mg/kg体重/天)没有任何有益的效果。我们没有发现支持兴奋性毒性在狂犬病病毒感染中起重要作用的证据。
Cultures derived from the cerebral cortices and hippocampi of 17-day-old mouse fetuses infected with the CVS strain of rabies virus showed loss of trypan blue exclusion, morphological apoptotic features, and activated caspase 3 expression, indicating apoptosis. The NMDA (N-methyl-D-aspartate acid) antagonists ketamine (125 mu M) and MK-801 (60 mu M) were found to have no significant neuroprotective effect on CVS-infected neurons, while the caspase inhibitor Ac-Asp-Glu-Val aspartic acid aldehyde (25 mu M) exerted a marked neuroprotective effect. Glutamate-stimulated increases in levels of intracellular calcium were reduced in CVS-infected hippocampal neurons. Ketamine (120 mg/kg of body weight/day intraperitoneally) given to CVS-infected adult mice produced no beneficial effects. We have found no supportive evidence that excitotoxicity plays an important role in rabies virus infection.