Mechanisms of Epilepsy Development
Temporal lobe epilepsy (TLE) commonly arises following long seizures early in life, especially long fever-associated seizures (febrile status epilepticus;; FSE). TLE, in addition to spontaneous seizures, is also commonly characterized by cognitive deficits. However, there are major gaps in our knowledge regarding the causal relationships of FSE and TLE, including its cognitive disturbances, and the mechanisms of how FSE can lead to TLE. To answer these questions a rodent model of experimental (e)FSE has been established, and, as in the human, a proportion of rats with eFSE develop TLE. This enables addressing fundamental questions that are required for diagnosis and intervention in humans: Which individuals with FSE will fall among the 40% that develop TLE? Are there predictive markers for those at risk? How does FSE provoke TLE and what are the mechanisms? Can we prevent FSE-provoked TLE and FSE-induced cognitive deficits? Addressing these questions is the goal and core of this thesis project.