| OCR Text |
Show 98 Viral-induced epilepsy is difficult to study experimentally because animals either die from acute viral encephalitis or do not develop spontaneous recurrent seizures (Beers et al., 1993; Griffith et al., 1967; Lehrmann et al., 2008; Wu et al., 2003). An ideal mouse model for interrogating the role of astrocytes in viral-induced epilepsy is the Theiler's Murine Encephalitis Virus (TMEV) model (Libbey et al., 2008). This model exhibits a robust immune response, characterized by high TNF-α mRNA levels, acute seizures and profound HC reactive astrocytosis (Kirkman et al., 2010b). TMEV infected mice remain chronically susceptible to seizures and a majority of infected mice develop epilepsy (Stewart et al., 2010). Following cortical injection of TMEV, the virus migrates and infects CA1 and CA2 pyramidal neurons causing profound astrogliosis throughout the hippocampus, including the dentate gyrus. This is similar to the hippocampus-tropic migration observed in herpes encephalitis (Lisé et al., 2006). The dentate gyrus serves a "gate" function in the hippocampus−information must pass through it to enter or leave the hippocampus−and breakdown of this function could lead to seizures (Kim et al., 2005; Wilson et al., 2005). It is notable that granule cells of the dentate gyrus are not infected by TMEV and survive (Libbey et al., 2008). However, due to the astrocytosis that develops in the dentate gyrus (Kirkman et al., 2010b), altered astrocyte activity may contribute to synaptic changes in granule cells and cause this region of the hippocampus to become hyperexcitable. We will therefore use the TMEV model to study the role of astrocyte glutamate release and TNF-α in epileptogenesis. It is plausible that following TMEV infection, high levels of TNF-α in the brain contribute to epileptogenesis by promoting calcium-dependent glutamate release from reactive astrocytes which can then affect synaptic scaling, lead to acute seizures and set the stage for development of epilepsy. Using the PC::G5-tdT reporter |
