Bumetanide could prevent prolonged convulsive seizures in epilepsy

Written by Hannah Makin

A recent study published in Annals of Neurology has investigated the mechanisms underlying the formation of aberrant neural connections observed after an epileptic seizure. At the root of these findings is an abnormal depolarizing GABAergic drive, which studies suggest accelerates brain activity and leads to this incorrect re-wiring of connections in the brain.
In this investigation, researchers at the University of Helsinki (Helsinki, Finland) studied rat epilepsy models to identify the relationship between GABA and the neural connections in the brain after a convulsive seizure.

As Research Director Claudio Rivera (University of Helsinki) explained, GABA was found to accelerate depolarizing activity in the brain, contributing to the formation of aberrant neural connections that are formed after a convulsive seizure occurs.

Findings also indicated new possibilities for the drug bumetanide as a future treatment option for those with epilepsy. Bumetanide is currently on the drug market as a diuretic for the treatment of heart failure.

In this study, the acceleration of brain activity caused by GABA was blocked by bumetanide for up to 3 days after the occurrence of an epileptic seizure.

Additionally, the number of abnormal neuronal connections was significantly lower when measured 2 months after the seizure took place. “Most importantly, the number of convulsive seizures diminished markedly,” stated Claudio.

Past research has already demonstrated bumetanide’s ability to prevent convulsive seizures in the acute phase. However, this is the first study that demonstrates bumetanide’s potential long-term effects on the neural wiring in the brain.

It may also be possible that a similar mechanism evokes the onset of epilepsy after a serious brain injury, thereby indicating another potential therapeutic use for bumetanide.

Claudio commented on what research still needs to be done in the area: “The next step is to study bumetanide both by itself and in combination with other clinically used drugs. We want to find out the ways in which it may offer additional benefits in the treatment of epilepsy in combination with and even in place of currently used antiepileptic drugs.”

Sources: Kourdougli N, Pellegrino C, Renko JM et al. Depolarizing γ-aminobutyric acid contributes to glutamatergic network rewiring in epilepsy. Ann. Neurol. doi:10.1002/ana.24870 (2017) (Epub ahead of print); https://helsinki.fi/en/news/new-mechanism-underlying-epilepsy-found