Interdepartmental Program in Neuroscience, University of Utah, Salt Lake City, Utah, USA.
Epilepsia. 2010 Aug;51(8):1418-28. doi: 10.1111/j.1528-1167.2009.02405.x. Epub 2009 Dec 1.
Central nervous system infections greatly increase the risk for the development of seizures and epilepsy (recurrent unprovoked seizures). We have previously shown that Theiler's murine encephalomyelitis virus (Theiler's virus or TMEV) infection causes acute symptomatic seizures in C57BL/6 (B6) mice. The objective of the present study was threefold: (1) to assess pathologic changes associated with acute TMEV infection and infection-induced seizures, (2) to determine whether Theiler's virus infection and associated acute seizures lead to chronically altered seizure susceptibility, and (3) to determine whether genetic background influences seizure susceptibility following Theiler's virus infection.
Immunohistochemical techniques were used to assess Theiler's virus antigen localization in the brain and associated neuronal cell death. A battery of electroconvulsive threshold (ECT) tests and corneal kindling studies were conducted to assess whether there were chronic alterations in seizure susceptibility and kindling development. Studies were conducted in both B6 and SJL/J mice to assess strain-dependent effects.
Histopathologic analyses indicate that TMEV has specific tropism for limbic structures and causes widespread cell death in these regions. Results from ECT studies demonstrate that B6 mice that displayed acute symptomatic seizures have significantly reduced seizure thresholds and kindle faster than either control mice or infected mice without acute seizures. Furthermore, these effects were mouse-strain dependent, since SJL/J mice displayed a different seizure threshold spectrum.
These findings indicate that Theiler's virus infection leads to chronically altered seizure susceptibility in mice. It is important to note that Theiler's virus infection of B6 mice represents a novel model to study postinfection hyperexcitability.
中枢神经系统感染大大增加了癫痫发作和癫痫（反复无诱因发作）的风险。我们之前已经表明，Theiler 鼠脑脊髓炎病毒（Theiler 病毒或 TMEV）感染会导致 C57BL/6（B6）小鼠出现急性症状性癫痫发作。本研究的目的有三：（1）评估与急性 TMEV 感染和感染诱导的癫痫发作相关的病理变化，（2）确定 TMEV 感染和相关的急性癫痫发作是否导致慢性改变的癫痫易感性，以及（3）确定遗传背景是否影响 TMEV 感染后的癫痫易感性。
免疫组织化学技术用于评估脑内 Theiler 病毒抗原定位和相关神经元细胞死亡。进行了一系列电惊厥阈值（ECT）测试和角膜点燃研究，以评估是否存在癫痫易感性和点燃发展的慢性改变。在 B6 和 SJL/J 小鼠中进行研究，以评估品系依赖性影响。
组织病理学分析表明，TMEV 对边缘结构具有特定的嗜性，并导致这些区域广泛的细胞死亡。ECT 研究结果表明，出现急性症状性癫痫发作的 B6 小鼠的惊厥阈值显着降低，并且比对照小鼠或没有急性癫痫发作的感染小鼠更快地点燃。此外，这些效应是小鼠品系依赖性的，因为 SJL/J 小鼠显示出不同的惊厥阈值谱。
这些发现表明，Theiler 病毒感染导致小鼠慢性改变的癫痫易感性。值得注意的是，B6 小鼠的 Theiler 病毒感染代表了研究感染后过度兴奋的新型模型。
