Japanese Encephalitis Virus-Induced Peripheral Neuropathy in the Rat Model

Abstract

Background: Guillain–Barré Syndrome Associated with Japanese encephalitis virus(JEV) infection,the mechanism of JEV which caused peripheral nerve injury remains unknown.Recently, it has been suggested that an altered sphingolipid metabolism may contribute to the pathogenesis of peripheral neuropathy. In light of the emerging evidence of peripheral nerve injury when JEV infected and the evidence in the pathogenesis of neuroimmunity, we aimed to make a rat model which peripheral nerve injury after JEV infection and investigate relevant damage mechanism. Methods: We investigated the infected rat with peripheral neuropathy induced by JEV. The rat exhibited behavioral and pathological signs of peripheral nervous injury. The motor function of rats were determined by clinical scoring and tissue examination.Electrophysiological measurements and transmission electron microscopy was used on sciatic nerves to assess peripheral peripheral nervous injury.ELISA were used to evaluate IFNγ, IL-17,ceramide and acid sphingomyelinase level. Immunofluorescence was performed on sciatic nerves to assess the expression and localization of ceramide and matrix metalloproteinase-9.Results: Japanese encephalitis virus induced peripheral neuropathy in rat,evidenced by the aggravated clinical scores, electrophysiological,transmission electron microscopy,circulating pro-inflammatory cytokines, and histological anomalies, suggesting that demyelination and axonal damage of sciatic nerves. JEV destroyed the tight junction structure of rat’s blood nerve barrier and increased ceramide and matrix metalloproteinase-9.Conclusion:These data suggest that JEV is a potential reason caused peripheral nerve injury in rat model and this model can be used for the investigation of the roles of various cytokines and acid sphingomyelinase,ceramide system in infection-induced peripheral neuropathy. Further investigation of this model could give a better understanding and lead to more effective evidences for JEV infection-associated peripheral neuropathy.