Laboratory of Veterinary Anatomy, College of Veterinary Medicine, Konkuk University, 120 Neungdongro, Gwangjingu, Seoul 143-729, Korea.
Vet Res. 2014 Jun 10;45(1):63. doi: 10.1186/1297-9716-45-63.
Influenza A virus infections have been proposed to be associated with a broad spectrum of central nervous system complications that range from acute encephalitis/encephalopathy to neuropsychiatric disorders in humans. In order to study early influenza virus exposure in the brain, we created an influenza-infection model in neonatal mice to investigate infection route and resulting pathological changes in the brain. Real-time polymerase chain reaction and immunohistochemical analyses showed that influenza virus infection induced by an intraperitoneal injection was first detected as early as 1 day post infection (dpi), and the peak infection was observed at 5 dpi. The viral antigen was detected in a wide range of brain regions, including: the cerebral cortex, hippocampus, cerebellum, and brainstem. Apoptotic cell death and gliosis were detected in the areas of viral infection. Significant increases in proinflammatory cytokine expression were also observed at 5 dpi. Viral RNAs were detected in the cerebrospinal fluid of infected adult mice as early as 1 dpi. In addition, many infected cells were observed near the ventricles, indicating that the virus may enter the brain parenchyma through the ventricles. These results demonstrate that influenza virus may effectively infect broad regions of the brain through the hematogenous route, potentially through the cerebrospinal fluid along the ventricles, and subsequently induce neuropathological changes in the neonatal mouse brain.
甲型流感病毒感染被认为与人类中枢神经系统的广泛并发症有关，范围从急性脑炎/脑病到神经精神疾病。为了研究早期流感病毒在大脑中的暴露情况，我们在新生小鼠中创建了一个流感感染模型，以研究感染途径和大脑中的病理变化。实时聚合酶链反应和免疫组织化学分析显示，通过腹腔注射诱导的流感病毒感染最早可在感染后 1 天（dpi）检测到，并且在 5 dpi 时观察到峰值感染。病毒抗原在广泛的脑区被检测到，包括大脑皮层、海马体、小脑和脑干。在病毒感染区域检测到凋亡细胞死亡和神经胶质增生。在 5 dpi 时还观察到促炎细胞因子表达的显著增加。在感染成年小鼠的脑脊液中，早在 1 dpi 就检测到病毒 RNA。此外，在脑室附近观察到许多感染细胞，表明病毒可能通过脑室进入脑实质。这些结果表明，流感病毒可能通过血源性途径有效地感染大脑的广泛区域，可能通过沿着脑室的脑脊液，并随后在新生小鼠大脑中引起神经病理变化。
