A signaling pathway known for its role in immune defense responses is also involved in epilepsy, according to a report in this week's Nature Medicine. The discovery could potentially be useful in the development of new anti-convulsant agents.
Brain inflammation is a major factor in epilepsy, but the impact of specific inflammatory molecules on the disease is not fully understood. Using several models of epilepsy in mice, Annamaria Vezzani and her colleagues discovered that release of a molecule called HMGB1 from neurons and glia and its interaction with a receptor key for the immune response against pathogens ― TLR4 ― promoted seizures.
The researchers also found that blocking the action of HMGB1 and TLR4 decreased seizure frequency. Mice lacking TLR4 were also resistant to manipulations known to induce seizures. Last, increased levels of HMGB1 and TLR4 in epileptogenic tissue from patients pointed to the potential human relevance of this mechanism, which could be targeted to develop new anticonvulsant agents.