Kastrukoff L F, Lau A S, Leung G Y, Thomas E E
Department of Medicine, University of British Columbia, Vancouver, Canada.
J Neurol Sci. 1993 Jul;117(1-2):148-58. doi: 10.1016/0022-510x(93)90167-w.
We previously reported that lip inoculation of Herpes simplex virus type I (HSV I) in specific strains of mice would induce multifocal brain demyelination (MBD). The mechanisms mediating the development of MBD are unknown. In this study, five inbred strains of mice (C57BL/6J, Balb/cByJ, A/J, SJL/J, PL/J) immunosuppressed with either irradiation (IR), cyclophosphamide (CY), or cyclosporin A (CP) along with three immune deficient strains (C57BL/6J nu/nu, Balb/cByJ nu/nu, C57BL/6J bg/bg) were lip inoculated with HSV I to determine the effect of immunosuppression on viral spread throughout the brain and the development of demyelination during the acute stage of infection. Mortality increased in all groups when compared with controls but was greatest in A/J, SJL/J, and PL/J strains, where all mice died before day 6 PI. In contrast with immunocompetent C57BL/6J mice where virus is restricted to the brainstem, virus spread throughout the brain of immunosuppressed C57BL/6J, C57BL/6J nu/nu, and C57BL/6J bg/bg mice. Despite viral spread throughout the brain of immunosuppressed C57BL/6J, C57BL/6J nu/nu, Balb/cByJ and Balb/cByJ nu/nu mice, MBD did not develop. MBD did develop however, in both HSV I infected C57BL/6J bg/bg and CP treated Balb/cByJ mice. Immunosuppression of HSV I infected Balb/cByJ mice prevents the development of demyelination at the trigeminal root entry zone (TREZ) of the brainstem while in Balb/cByJ nu/nu mice, the extent of demyelination at TREZ was reduced and delayed when compared with immunocompetent controls. These results suggest that the immune system plays an important role in limiting viral spread in the brain as well as in the development of demyelination at TREZ and of MBD throughout the brain during the acute phase of infection. Virus alone does not induce MBD in this animal model of virus induced CNS demyelination but is a prerequisite for its development.
我们之前报道过，在特定品系的小鼠中经唇部接种单纯疱疹病毒I型（HSV I）会诱发多灶性脑脱髓鞘（MBD）。介导MBD发生发展的机制尚不清楚。在本研究中，对5个近交系小鼠（C57BL/6J、Balb/cByJ、A/J、SJL/J、PL/J）分别用辐射（IR）、环磷酰胺（CY）或环孢素A（CP）进行免疫抑制，同时选取3个免疫缺陷品系（C57BL/6J nu/nu、Balb/cByJ nu/nu、C57BL/6J bg/bg），经唇部接种HSV I，以确定免疫抑制对病毒在脑内扩散以及感染急性期脱髓鞘发生发展的影响。与对照组相比，所有组的死亡率均升高，但在A/J、SJL/J和PL/J品系中死亡率最高，所有这些品系的小鼠在感染后第6天前全部死亡。与免疫功能正常的C57BL/6J小鼠（病毒局限于脑干）不同，免疫抑制的C57BL/6J、C57BL/6J nu/nu和C57BL/6J bg/bg小鼠的病毒扩散至全脑。尽管免疫抑制的C57BL/6J、C57BL/6J nu/nu、Balb/cByJ和Balb/cByJ nu/nu小鼠的病毒扩散至全脑，但并未发生MBD。然而，在感染HSV I的C57BL/6J bg/bg小鼠和经CP处理的Balb/cByJ小鼠中均发生了MBD。对感染HSV I的Balb/cByJ小鼠进行免疫抑制可防止脑干三叉神经根进入区（TREZ）发生脱髓鞘，而在Balb/cByJ nu/nu小鼠中，与免疫功能正常的对照组相比，TREZ处的脱髓鞘程度减轻且延迟。这些结果表明，免疫系统在限制病毒在脑内扩散以及在感染急性期TREZ处脱髓鞘和全脑MBD的发生发展中起重要作用。在这种病毒诱导的中枢神经系统脱髓鞘动物模型中，仅病毒本身不会诱发MBD，但却是其发生发展的一个先决条件。
