Abstracts

Rationale: Epilepsy affects 60 million people worldwide. Despite the development of antiepileptic drugs, up to 35% of patients are drug refractory with uncontrollable seizures. Toll-like receptors (TLRs) are a central component of the non-specific innate inflammatory response. Because TLR3 was recently implicated in neuronal plasticity, we hypothesized that it may contribute to the development of epilepsy after status epilepticus (SE). Methods: We used the pilocarpine model for SE in TLR3-deficient mice and their respective wild-type controls. In this model, a single SE event leads to spontaneous recurrent seizures (SRS). Two weeks after SE, mice were implanted with wireless electro-encephalogram (EEG) transmitters to quantify up to one month after SE. The impact of TLR3 deficiency on SE was assessed using separate cohorts of mice regarding EEG activity, seizure progression, hippocampal microglial cell distribution, and the expression of the pro-inflammatory cytokines Interleukin (IL)-1߬ IL-18, IL-6, Tumor Necrosis Factor (TNF)a and interferon (IFN)߮ Results: TLR3 deficiency significantly reduced SRS, augmented hippocampal volume, increased microglial cell number, reduced pro-inflammatory cytokine levels and increased survival following SE. Conclusions: This study reveals novel insights into the pathophysiology of epilepsy and the contribution of TLR3 to disease progression. Our results identify the TLR3 pathway as a potential future therapeutic target in SE. Funding: Research was funded by a local research grand from the collaboration of Rabin Medical Center and the Bar Ilan University.