关键词：创伤性脑损伤；癫痫；海马
摘 要：Traumatic Brain Injury (TBI) is a well-established inducer of temporal lobe epilepsy (TLE), a frequently medically intractable and permanent epilepsy syndrome. Unlike many TLE models, which cause global brain injury that do not replicate the human condition, or other TBI models, which do not induce TLE reliably, the controlled cortical impact (CCI) model of posttraumatic epilepsy in mice results in localized cell loss, synaptic reorganization, and development of TLE. Abnormalities in inhibitory neurotransmission are important aspects of TLE in several animal models. Under this award, the CCI model was established in all three collaborating laboratories. Specific parameters of injury associated with epileptogenesis were determined. It was determined that upregulation of the JaK/STAT3 pathway in the injured hippocampus occurs after CCI, which could be blocked by post-injury administration of a JaK/STAT3 inhibitor. Blocking JaK/STAT3 activity did not prevent loss of GABA cells in the injured hippocampus. Inhibitory postsynaptic currents in the dentate gyrus ipsilateral to the injury were reduced in frequency weeks after the injury, recapitulating findings in other models in which aspects of epileptogenesis were attenuated by STAT3 inhibition. These results critically establish model parameters and control measurements, and provide the basis for remaining proposed experiments.