valacyclovir and Infections

Topics: Cytomegalovirus; Cytomegalovirus Infections; Double-Blind Method; Female; Humans; Infections; Infectious Disease Transmission, Vertical; Pregnancy; Secondary Prevention; Valacyclovir

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.

Topics: Acyclovir; Animals; Antiviral Agents; Behavior, Animal; Body Weight; Disease Susceptibility; Dose-Response Relationship, Drug; Drug Interactions; Electroencephalography; Electromyography; Herpes Simplex; Herpesvirus 1, Human; Hippocampus; Immunohistochemistry; Infections; Male; Mice; Mice, Inbred BALB C; Pentylenetetrazole; Reaction Time; Seizures; Staining and Labeling; Time Factors; Valacyclovir; Valine; Virus Latency