Abstracts

Rationale: Cortical dysplasia is a common pathological substrate in a large number of patients with medically intractable epilepsy. The expression of seizures and epilepsy in patients with these congenital malformations is variable but usually follows a second hit (e.g. trauma, infection). We previously described the development of EEG biomarkers of epileptogenicity (spikes and spontaneous seizures) following a second hit in rats with in utero radiation induced cortical dysplasia. The mechanisms of epileptogenesis in these animals remain unknown. Recent reports presented clinical correlations between activation of innate and adaptive immune system and changes in neuronal networks leading to epileptogenesis. Our goal was to investigate the role of peripheral immune system in epilepsy. Methods: We used a model of acute provoked seizure induced by intraperitoneal PTZ injection in normal and epilepsy prone cortical dysplasia (XRT) Sprague-Dawley rats to evaluate T cell distribution and phenotype within the brain and in the periphery by flow cytometry. Results: Both normal and XRT rats demonstrated 30% decrease in spleen weight 48 hours following seizure. This reduction is spleen size was mainly due to the decrease in numbers of CD3+ CD4 and CD8 T lymphocytes (from 30% to 3%). At the same time (day 2 post-seizure), there was a significant increase in CD4 and CD8 T cells infiltrating the brain cortex and hippocampus (increased up to 10%), but not cerebellum. Brain-infiltrating cells uniformly expressed CD44, a cell surface marker of activated effector and memory T lymphocytes. Spleen size and splenic T cell numbers recovered to pre-seizure levels by day 15 after seizure in both normal and XRT rats. The CD4 and CD8 T cell counts in the brain of normal rats declined to basal levels by day 30 post-seizure (1-3% of brain cells). Notably, T cells with CD4+CD44+ phenotype accumulated in the brains of XRT rats (5-15% of brain cells), while brain-infiltrating CD8 T cells in these rats declined to the similar counts as in normal control rats. Conclusions: Our findings indicate a massive relocation of T cells from the periphery into the brain following a single chemically-induced seizure and suggest a possible role for T cells in epileptogenesis. The information on how T cells function in the brain and interact with neurons and other brain cells during and after seizure may translate into better understanding of the mechanisms of epileptogenesis and the introduction of novel therapies in patients at risk for the development of epilepsy.