| Description |
Around 70 million people worldwide suffer from epilepsy, a neurological disorder that causes unprovoked and persistent seizures. A dominant cause of acquired epilepsies are from injuries to the central nervous system (CNS), such as viral infection of the CNS that results in brain inflammation (encephalitis). To study how viral encephalitis results in seizures, we use a mouse model of viral-induced epilepsy. In this model, C57BL/6J mice are intracerebrally injected with Theiler's murine encephalomyelitis virus (TMEV). Disease progression is demonstrated by an acute seizure phase followed by a latent phase, where no seizures are observed, followed by spontaneous recurrent seizures (epilepsy). It has been established that the innate immune system is implicated in the CNS inflammation that induces seizures. Specifically, activation of microglia and infiltration of peripheral macrophages into the brain together with the secretion of pro-inflammatory cytokines are associated with seizure development. The Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) was found to be exclusively and highly expressed by peripherally infiltrating macrophages during acute phase seizures. TREM-1 activation has been related to pro-inflammatory cytokine secretion. In this project, we used the mouse model of viralinduced epilepsy to study whether TREM-1 infiltrating macrophages play a role in seizure development by utilizing genetically modified mice lacking TREM-1. We evaluated both spontaneous and handling behavioral seizures. While there was no significant difference in spontaneous seizures, we found decreased behavioral seizure incidence and seizure severity in mice lacking TREM-1 during the acute phase of the infection. This suggests that TREM-1 plays a role in the development of acute phase seizures following viral encephalitis. Moreover, we found that cellular infiltration and macrophage activation in the CNS did not differ between wild type mice and mice lacking TREM-1. These studies allow us to learn more about how the inflammatory immune response to viral encephalitis relates to epileptogenesis and may reveal a novel therapeutic target to treat seizures and epilepsy in high-risk groups. |
