Abstracts

Rationale: Inflammation of the brain has received widespread attention as an important factor in acquired epileptogenicity, but the effect of specific inflammation mediators on neuron excitability has not yet been clarified. Recently, Maroso et al. reported that epileptogenic pathways are activated when high-mobility group box-1 (HMGB1) released from neurons and glia bind to toll-like receptor 4 (TLR4), a receptor that plays an important role in natural immunity. Therefore, to clarify inflammation mediator expression in intractable temporal lobe epilepsy patients, we used the hippocampus specimens of operated epilepsy patients to perform immunostaining for HMGB1, receptors TLR-2 and -4, and the receptor for advanced glycation end products (RAGE), investigating the expression of each of them Methods: This study targeted 19 patients who underwent resection surgery of the hippocampus or temporal lobe as treatment for intractable epilepsy at the Juntendo School of Medicine, Department of Neurosurgery from November 2004 through March 2012. Three specimens, including the patients of the same age range of 42 years , were used as controls. Immunostaining was performed for TLR2, TLR4, HMGB1, and RAGE receptors, and results were comparatively investigated. Results: Strong immune reactions for HMGB1, TLR2, and RAGE were observed in the pyramidal neurons, astrocytes, and microglia of epilepsy patients' cortical specimens. Meanwhile, in control cortexes, HMGB1 was detected in ubiquitous glia and neuron nuclei, but we did not observe TLR4 or RAGE expression. Conclusions: This study suggests that expression of HMGB1 and TLR4 increases in the epileptogenic site of the human brain and that HMGB1-TLR4 pathway also plays an important part in human epileptogenis. It was found that in human hippocampal epilepsy, HMGB1 has prolonged action in localized areas and TLR4 becomes involved. This may lead to hippocampal sclerosis and atrophy.