Valtrex treatment prevents seizures in infected mice

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Exp Neurol. 2004 Sep;189(1):66-77.

Valacyclovir

treatment ameliorates the persistently increased

pentylenetetrazol-induced seizure susceptibility in mice with herpes

simplex virus type 1 infection.

Wu HM ... Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan 701, Taiwan.

Herpes

simplex virus type 1 (HSV-1) is an important pathogen related to

epilepsy. We have shown previously that corneal inoculation of mice

with HSV-1 causes acute spontaneous behavioral and electrophysiological

seizures and increases hippocampal excitability and kainite-induced

seizure susceptibility. In this study, we aimed to determine whether

early-life HSV-1 infection in mice might cause short- and long-term

enhanced susceptibility to pentylenetetrazol (PTZ)-induced seizures and

to evaluate whether early antiviral drug therapy was effectively

ameliorating this deficit. Seizure threshold was calculated by the

latency of onset of the myoclonic jerk, generalized clonus, and maximal

tonic-clonic convulsion. We demonstrate that the localization of viral

antigens was predominantly within the bilateral temporal areas

(amygdala, piriform, and entorhinal cortex) of HSV-1-infected mice. We

also present evidence that mice of all HSV-1-infected groups had a

shorter latency and higher severity to PTZ-induced seizures than in

age-matched, mock-infected controls. Treatment of HSV-1-infected mice

with valacyclovir, a potent inhibitor of HSV-1 replication, produced a

dose-dependent decrease in the signs of neurological deficits,

pathological damages, and PTZ-induced seizure severity. Our results are

consistent with the hypothesis that early-life HSV-1 infection leads to

persistent enhancement of neuronal excitability in limbic circuits,

which could result in an overall increased propensity to induce

seizures later in life. Additionally, prompt optimal antiviral therapy

effectively decreases seizure susceptibility in HSV-1-infected mice by

limiting the level of viral replication and inflammatory response

induced by virus. The present study provides not only experimental

evidence, but also a new therapeutic strategy in HSV-1-associated human

epilepsy. MID: 15296837