Understanding complexities of synaptic transmission in medically intractable seizures: A paradigm of epilepsy research

Abstract

Investigating the changes associated with the development of epileptic state in humans is complex and requires a multidisciplinary\rapproach. Understanding the intricacies of medically intractable epilepsy still remains a challenge for neurosurgeons across\rthe world. A significant number of patients who has undergone resective brain surgery for epilepsy still continue to have\rseizures. The reason behind this therapy resistance still eludes us. Thus to develop a cure for the difficult to treat epilepsy, we\rneed to comprehensively study epileptogenesis. Although various animal models are developed but none of them replicate\rthe pathological conditions in humans. So the ideal way to understand epileptogenecity is to examine the tissue resected for\rthe treatment of intractable epilepsy. Advanced imaging and electrical localization procedures are utilized to establish the\repileptogenic zone in epilepsy patients. Further molecular and cytological studies are required for the microscopic analysis of\rbrain samples collected from the epileptogenic focus. As alterations in inhibitory as well as excitatory synaptic transmission\rare key features of epilepsy, understanding the regulation of neurotransmission in the resected surgery zone is of immense\rimportance. Here we summarize various modalities of in vitro slice analysis from the resected brain specimen to understand\rthe changes in GABAergic and glutamatergic synaptic transmission in epileptogenic zone. We also review evidence pertaining\rto the proposed role of nicotinic receptors in abnormal synaptic transmission which is one of the major causes of epileptiform\ractivity. Elucidation of current concepts in regulation of synaptic transmission will help develop therapies for epilepsy cases\rthat cannot me managed pharmacologically.