Presentation description

Epilepsy, a neurological condition affecting 70 million people worldwide, is characterized by recurrent seizures that can significantly impact quality of life. Despite the efficacy of antiseizure medications, they do not work for 1/3 of patients. Brain inflammation induced by a central nervous system (CNS) viral infection plays a significant role in seizure development; understanding these mechanisms can support the discovery of new treatments. In a mouse model of viral-induced epilepsy, C57BL/6J mice intracranially (IC) infected with Theiler's Murine Encephalomyelitis Virus (TMEV) develop acute seizures from 3-7 days post-infection (dpi), followed by epilepsy (30dpi). Infiltration of inflammatory blood macrophages into the brain and secretion of inflammatory cytokines play a critical role in seizure development. Previous studies using non-infectious models demonstrated that Pioglitazone, a PPAR agonist, reduces seizures. Others have shown that Pioglitazone can polarize macrophages towards an anti-inflammatory phenotype. However, whether Pioglitazone modulates seizures following a CNS-viral infection remains unknown. Thus, we hypothesized that Pioglitazone treatment will promote anti-inflammatory macrophages, decreasing CNS inflammation and reducing seizures in TMEV-infected mice. C56BL6/J mice were IC infected with TMEV, and orally administered Pioglitazone daily (30mg/kg). Seizures were evaluated 2x/day (3-7 dpi). Contrary to our hypothesis, we observed greater seizure burden and incidence in Pioglitazone-treated mice. We speculate that Pioglitazone is polarizing not only macrophages, but also cells such as microglia, impairing their ability to present viral antigens to T cells, which are critical for reducing CNS-viral load. We are continuing to explore the role of Pioglitazone in modulating neuroinflammation, and its potential mechanisms in modifying seizures.