期刊
EXPERIMENTAL NEUROLOGY
卷 354, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2022.114087
关键词
Epilepsy; NMDAR; GluN2B; hippocampus; Ifenprodil; Seizure
资金
- National Science Center of Poland [2015/19/D/NZ7/02402]
- Foundation for Polish Science
This study investigates the role of GluN2B in the pathophysiology of temporal lobe epilepsy and suggests the potential therapeutic use of ifenprodil, a GluN2B selective NMDAR antagonist. The findings provide insights into the factors contributing to recurrent seizures and propose a new candidate treatment for temporal lobe epilepsy.
GluN2B is an NMDAR subunit that displays restricted expression in the mature hippocampus - a structure playing a major role in temporal lobe epilepsy. However, the contribution of GluN2B to the pathophysiology of the condition has not been fully explored. Here we combined status epilepticus models of temporal lobe epilepsy, protein expression studies, and patch-clamp experiments to demonstrate the profound change in the nature of glutamatergic transmission mediated in the epileptiform hippocampus by a subpopulation of GluN2B-containing NMDAR receptors. Satisfactory control of chronic seizures in temporal lobe epilepsy is still impossible for about 40% of patients. Therefore, new therapeutic approaches against the condition are desired. Using video-EEG recordings in animals and ex vivo extracellular recordings in brain sections, we present here the potential of ifenprodil (GluN2B selective NMDAR antagonist) for altering the course of epileptogenesis and ictogenesis in temporal lobe epilepsy. In sum, we identify GluN2B as one of the factors in the pathogenesis of recurrent seizures and provide a rationale for clinical studies on ifenprodil as a new candidate therapeutic against temporal lobe epilepsy.
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