Modulation of abnormal neuronal circuit in temporal lobe epilepsy

OBJECTIVE Temporal lobe epilepsy(TLE)is one of the most common types of human epilepsy,and they are often resistant to current treatments.METHODS By using optogenetic,electrophysiological,imaging and pharmacology strategies,we aimed toinvestigate the underlying circuit mechanism of TLE and tried to developthe novel and efficient approach to control epilepsy.RESULTS(1)Using micro PET and multichannel EEG recording,we found an abnormal neural network,characterized by early hypometabolism and after discharge spread,during the epileptogenensis of TLE.(2)Deep brain stimulation,especially low frequency stimulation,targeted the epileptic focus and the areas outside of the focus(critical regions for seizure spread),such as the piriform cortex,cerebellum,entorhinal cortex or subiculum,reduced seizure severity in TLE.Its anti-epileptic effect is time-window dependent and polarity dependent,which shows a promising strategy for treating epileptic seizures.(3)Using an optogenetic strategy,we demonstrated that excitatory projection from entorhinal cortex to hippocampus instructs the brain-stimulation treatments of epilepsy.(4)Our data from both the clinical and experimental studies further demonstrated that a disinhibitory GABAergic neuronmediated microcircuit in the subiculum contributes to secondary generalized seizures in TLE.(5)Finally,based on abnormal synchronization of the electrical activity in epileptic circuit,we developed electroresponsive hydrogel nanoparticles modified with angiopep-2 to facilitate the delivery of the antiepileptic drug phenytoin sodium,which greatly improves the therapeutic index.CONCLUSION Our findings may update the current view of epileptic neuronal networks and suggest possible promising ways for epilepsy treatment.