Abstracts

Rationale: Cortical dysplasia is a common pathological substrate in a large number of patients with medically intractable epilepsy. Development of seizures and epilepsy in patients with these congenital malformations is variable, but usually follows a “second hit” such as trauma. 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. In addition, recent reports presented clinical correlations between activation of innate and adaptive immune system and changes in neuronal networks leading to epileptogenesis. However, the direct role of T cells in epilepsy is unknown. Our goal was to investigate the role of brain-infiltrating T cells in development of epilepsy.Methods: We used a model of acute provoked seizure induced by intraperitoneal PTZ injection in normal (NL) and epilepsy prone cortical dysplasia (XRT) Sprague-Dawley rats to generate brain-infiltrating T cells. We then isolated T cells from brains of NL and XRT rats 15 days post PTZ induced seizure. These purified T cells were then transferred intraventricularly into XRT or NL rats in a 10 μl volume. As control, 10 μl of PBS was injected into NL or XRT rats. Following the T cell transfer and epidural electrode implantation, rats were monitored by EEG for 3 days. On day 8 post T cell transfer, PTZ threshold was tested in rats with and without T cells. Our results indicated that intraventricular PBS injection in both NL and XRT rats resulted in SZ induction (20, 26 on average for NL and XRT respectively) during the first 8 hours post-surgery.Results: SZs continued in XRT rats up to 3 days post injection. Rats transferred with T Cells however, demonstrated significantly lower numbers of SZs post trauma (0, 5.2 on average for NL and XRT rats respectively). Furthermore, PTZ threshold for XRT rats with transferred T cells was higher than XRT control and XRT animals injected with PBS.Conclusions: These data suggests that brain-infiltrating T cells following SZs may have a protective effect on SZ development, especially in epilepsy prone rats. Further information on the identity of these T cells and their cytokine and chemokine production is needed for future therapeutic potential. However, investigating how T cells function in the brain and interact with neurons and other brain cells during and after seizure may lead to better understanding of the mechanisms of epileptogenesis and the eventual introduction of novel therapies in patients at risk for the development of epilepsy.