Astrocytes play a key role in regulating aspects of
inflammation and in the homeostatic maintenance of the central nervous system (CNS). However, the role of astrocytes in
viral encephalitis mediated
inflammation is not well documented. As Japanese encephalitis virus (JEV)
infection is localized to neurons and considering the importance of astrocytes in supporting neuronal survival and function, we have exploited an experimental model of
Japanese encephalitis (JE) to better understand the role of astrocytes in JE. Suckling mice pups were inoculated with the virus and 2 and 4 days later we analyzed a panel of molecules characteristic of reactive
astrogliosis. We show that JEV
infection increases the expression of astrocyte-specific
glial fibrillary acidic protein (GFAP), the
glutamate aspartate transporter (GLAST),
glutamate transporter-1 (GLT-1) and
ceruloplasmin (CP). The transcript levels of
growth factors produced predominantly by activated astrocytes such as
nerve growth factor (
NGF) and ciliary
neurotrophin factor (
CNTF) were elevated following JEV
infection. The transcript level of
brain-derived neurotrophic factor (
BDNF) was also elevated following JEV
infection. Both
NGF and
CNTF were capable of preventing ROS mediated neuronal death following in vitro JEV
infection to a certain extent. Taken altogether, these data indicate that increased
astrogliosis following JEV
infection is accompanied by the enhanced ability of astrocytes to detoxify
glutamate, inactivate
free radical and produce
neurotrophic factors that are involved in neuronal protection. However, this elevated physiological state of astrocyte is insufficient in conferring neuroprotection, as infected animals eventually succumb to
infection. The response of astrocytes to JE can be amplified to modulate the adaptive response of brain to induce neuroprotection.