Brain injuries or seizures cause the damaged brain cells to release high mobility group box-1 (HMGB1), a protein that binds to its receptors (including TLR4) and plays a central role in inducing inflammation, brain damage, and abnormal brain activity. In this project, we will use an animal model to determine brain injury-induced changes in HMGB1 and its receptors and their contribution to the development of epilepsy. We will also directly test whether neutralizing HMGB1 will prevent posttraumatic epilepsy. Because targeting HMGB1 may promote brain repair and can be achieved with several currently available drugs or molecules, this strategy may have great potential for clinical application.
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