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Show 58 acute CNS infection. For instance, herpes simplex virus encephalitis (HSVE) in rodents, a model characterized by clinical signs of viral illness and acute behavioral seizures, is one of the most widely studied models of infection-induced seizures (Wu et al., 2003; Solbrig et al., 2006). However, while chronically enhanced hippocampal excitability and seizure susceptibility have been reported in herpes simplex virus type-l (HSV -1) infected mice, only about 50% of mice survive the acute infection (Wu et al., 2003; Wu et al., 2004). Moreover, spontaneous motor seizures have not been observed and alterations in seizure thresholds could possibly be attributed to lifetime persistence of low viral titers. Recently, we reported a novel model whereby C57BLl6 (B6) mice infected with Theiler's murine encephalomyelitis virus (Theiler'S virus or TMEV) develop acute encephalitic seizures (Libbey et al., 2008). TMEV belongs to the Picornaviridae family, which is a relatively large and clinically relevant family of nonenveloped, positive stranded RNA viruses that includes members such as hepatitis A, poliovirus and human rhinoviruses (common cold) (Buenz and Howe, 2006). Intracerebral inoculation of susceptible strains of mice induces a biphasic disease consisting of acute encephalitis and chronic demyelination in susceptible strains of mice (Monteyne et al., 1997). In contrast, resistant mouse strains such as B6 develop only acute encephalitis and completely clear the virus within 2-4 weeks postinfection (p.i.) (Tsunoda and Fujinami, 1996). In addition to acute spontaneous neuron acute seizures, B6 mice also display significant hippocampal pyramidal pyknosis and increased transforming growth factor (TGF)-B expression during the encephalitis (Buenz et al., 2006; Libbey et al., 2008). Further studies show that TMEV-infected B6 mice exhibit chronically reduced seizure thresholds and increased susceptibility to kindling acquisition (Chapter 2). These findings suggest that TMEV- |
