Harnessing the Brain's Plasticity to Acquire Epilepsy Resilience

Patients with epilepsy must take medicine to manage seizures. Even then, only 65% are able to control their symptoms, rendering invasive surgery the only cure. Now, a research group has investigated a new stimulation paradigm that could cultivate greater resistance to epilepsy.

Epilepsy resilience can be created by enhancement of suppressive system.

Around 1% of the world's population lives with epilepsy; yet only 65% of epilepsy patients can manage their symptoms with medication. Currently, surgically removing the lesion in the brain responsible for the condition is the only radical cure for epilepsy. Still, many patients have to take medication for the rest of their life to deal with their seizures.

A research group led by professor Ko Matsui from the Super-network Brain Physiology Lab at Tohoku University reported on a stimulation paradigm used on experimental animals that could potentially cultivate resilience to epilepsy.

Frequent seizure-evoking stimulation to the brain has been shown to induce epileptogenesis and epileptic brain conditions. To the researcher's surprise, however, repeated stimulation resulted in a dramatic decrease in the seizure response to the stimulus.

"Our brain has an infinite ability for plasticity," says Matsui. "If an epileptic state can be created, we must query whether it is also conceivable to reverse the transition or to override the existing hyper-excitable circuit with an additional suppressive system."

Using optogenetics technology to control the activity, Dr. Yoshiteru Shimoda, Matsui and their team demonstrated that a specific stimulation paradigm prompted the release of the endogenous inhibitory transmitter adenosine from glial cells. This converted the rat's brain to a state strongly resistant to seizures.

Details of their findings were published in Neurobiology of Disease online

Matsui is cautiously optimistic. "Although epileptogenesis unfortunately could not be reversed, we showed we could invoke the homeostatic nature of the brain circuit to contain hyper-excitation."

For the current study, light-sensitive proteins were genetically expressed in neurons to regulate moderate neuron-to-glial signaling at will. Such optogenetic technology would be difficult to apply in human patients, noted Matsui.

"Despite clinical use being a long way off, it is possible to imagine a future where a therapeutic strategy can directly target glial cells and enable the creation of an epileptic resistant state."

Published: 17 Jan 2022


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Title: Optogenetic stimulus-triggered acquisition of seizure resistance
Authors: Yoshiteru Shimoda, Kaoru Beppu, Yoko Ikoma, Yosuke M. Morizawa, Satoshi Zuguchi, Utaro Hino, Ryutaro Yano, Yuki Sugiura, Satoru Moritoh, Yugo Fukazawa, Makoto Suematsu, Hajime Mushiake, Nobukazu Nakasato, Masaki Iwasaki, Kenji F. Tanaka, Teiji Tominaga, Ko Matsui
Journal: Neurobiology of Disease
DOI: https://doi.org/10.1016/j.nbd.2021.105602