Role for GABA in accelerating brain activity - new mechanism for epilepsy

Following a prolonged epileptic seizures  neural connections of the brain may be rewired in an incorrect way. This may result in seizures that are difficult to control with medication. Mechanisms underlying this phenomenon are not entirely known, which makes current therapies ineffective in some patients.

In a study, published in the Annals of Neurology, researchers at the Neuroscience Center of the University of Helsinki have shown a role for gamma-aminobutyric acid (GABA), a main neurotransmitter in the brain, in the glutamatergic network rewiring in the brain. Rewiring of excitatory glutamatergic neuronal circuits is a major abnormality in epilepsy.

After a prolonged convulsive seizure, instead of the usual inhibitory effect of the transmitter, GABA accelerates brain activity. This, in turn, creates new, harmful neural connections.

Using a rat model of epilepsy they also found that accelerating effect of GABA was blocked for three days with a drug called bumetanide given soon after a seizure. The number of harmful connections detected in the brain was significantly lower two months later. Although there is extensive literature on the role of bumetanide in the acute treatment of seizures, this study has shown for the first time, that bumetanide has a long term effect on the neural network structure of the brain.

Citation

Nazim Kourdougli, Christophe Pellegrino, Juho-Matti Renko, Stanislav Khirug, Geneviève Chazal, Tiina-Kaisa Kukko-Lukjanov, Sari E. Lauri, Jean-Luc Gaiarsa, Liang Zhou, Angélique Peret, Eero Castrén, Raimo K. Tuominen, Valérie Crépel, Claudio Rivera. Depolarizing γ-aminobutyric acid contributes to glutamatergic network rewiring in epilepsy. Annals of Neurology, 2017; 81 (2): 251 DOI: 10.1002/ana.24870

Source: Helsingin yliopisto (University of Helsinki)

Cover: The amount of harmful nerve connections is significantly lower (far right, arrows) when treating with bumetanide after a prolonged convulsive seizure. Credit: Nazin Kourdougli