Although infectious agents contribute to epilepsy, seizures can also be elicited through inflammatory pathways in sterile conditions. Vezzani and her colleagues demonstrate in both acute and chronic models of epilepsy that HMGB1, a protein normally found in the nucleus, is released by damaged or highly stressed cells and, by binding TLR4, lowers seizure threshold and increases time spent in seizures. Selective inhibition of this pathway retards seizure generation, suggesting new targets for anticonvulsant therapy (pages 369–370).
- Mattia Maroso
- Silvia Balosso
- Annamaria Vezzani