Farahtaj Firozeh, Alizadeh Leila, Gholami Alireza, Khosravy Mohammad Sadeq, Bashar Rouzbeh, Gharibzadeh Safoora, Mahmoodzadeh Niknam Hamid, Ghaemi Amir
National Center for Reference & Research on Rabies, Institut Pasteur of Iran, Tehran, Iran.
Department of Virology, Pasteur Institute of Iran, Tehran, Iran.
Iran J Basic Med Sci. 2021 Jul;24(7):943-950. doi: 10.22038/ijbms.2021.54264.12188.
The mechanisms of rabies evasion and immunological interactions with the host defense have not been completely elucidated. Here, we evaluated the dynamic changes in the number of astrocytes, microglial and neuronal cells in the brain following intramuscular (IM) and intracerebral (IC) inoculations of street rabies virus (SRV).
The SRV isolated from a jackal and CVS-11 were used to establish infection in NMRI-female mice. The number of astrocytes (by expression of GFAP), microglial (by Iba1), and neuronal cells (by MAP-2) in the brain following IM and IC inoculations of SRV were evaluated by immunohistochemistry and H & E staining 7 to 30 days post-infection.
Increased numbers of astrocytes and microglial cells in dead mice infected by SRV via both IC and IM routes were recorded. The number of neuronal cells in surviving mice was decreased only in IC-infected mice, while in the dead group, this number was decreased by both routes.The risk of death in SRV-infected mice was approximately 3 times higher than in the CVS-11 group. In IC-inoculated mice, viral dilution was the only influential factor in mortality, while the type of strain demonstrated a significant impact on the mortality rate in IM inoculations.
Our results suggested that microglial cells and their inflammatory cytokines may not contribute to the neuroprotection and recovery in surviving mice following intracerebral inoculation of SRV. An unexpected decrease in MAP2 expression via intramuscular inoculation indicates the imbalance in the integrity and stability of neuronal cytoskeleton which aggravates rabies infection.
狂犬病逃避宿主防御的机制以及与宿主防御的免疫相互作用尚未完全阐明。在此，我们评估了肌肉注射（IM）和脑内注射（IC）街狂犬病毒（SRV）后小鼠大脑中星形胶质细胞、小胶质细胞和神经元细胞数量的动态变化。
从豺狼分离的SRV和CVS-11用于在NMRI雌性小鼠中建立感染。通过免疫组织化学和苏木精-伊红（H&E）染色评估感染后7至30天IM和IC接种SRV后大脑中星形胶质细胞（通过GFAP表达）、小胶质细胞（通过Iba1）和神经元细胞（通过MAP-2）的数量。
记录到通过IC和IM途径感染SRV的死亡小鼠中星形胶质细胞和小胶质细胞数量增加。仅在IC感染的存活小鼠中神经元细胞数量减少，而在死亡组中，两种途径该数量均减少。SRV感染小鼠的死亡风险比CVS-11组高约3倍。在IC接种的小鼠中，病毒稀释是死亡率的唯一影响因素，而毒株类型对IM接种的死亡率有显著影响。
我们的结果表明，小胶质细胞及其炎性细胞因子可能对脑内接种SRV后存活小鼠的神经保护和恢复没有贡献。肌肉注射导致MAP2表达意外下降，表明神经元细胞骨架的完整性和稳定性失衡，这加剧了狂犬病感染。
