Reversing effects of epilepsy

15 February 2017


Rat brain COX-2 activity during a seizure.


More than 150 years ago the Irish-born physician Robert Todd penned the first description of the phenomenon now known in his honour as "Todd's Paresis". This is a temporary yet debilitating muscle weakness that follows an epileptic seizure. And, usually, patients who suffer seizures frequently complain of subsequent drowsiness, confusion and memory impairment for an hour or more after a fit.

These manifestations had been attributed to "exhaustion" in the cerebral cortex brought on by the intense neurological activity that accompanies a seizure. But now experiments by Canadian scientists, and confirmed in human epilepsy patients, has found the real reason for these disabling symptoms as well as a simple way to block them.

Writing in eLife, University of Calgary scientist Cam Teskey and his colleagues have discovered that molecules released during a seizure by excited brain cells trigger arteries supplying the brain to constrict, limiting the flow of blood to the tissue.

This effect, which persists for an extended period after a seizure, deprives the affected brain cells of oxygen and sugars preventing them from working properly and causing the functional deficits experienced by the patient.

Teskey and his team made the discovery by implanting sensitive oxygen sensors into the brains of epileptic rats. Whenever the animals had a seizure, the team recorded dangerously low levels of oxygen in different brain territories afterwards.

This, they subsequently found, was preceded by an increase in the levels of an enzyme called cyclooxygenase, which produces signals that cause blood vessels to constrict.

Dosing the animals with drugs that either block the action of cyclooxygenase, or stop blood vessels from constricting, abolished the oxygen dip and prevented the functional problems that would both normally follow a fit. This effect also occurs in humans, Teskey's team have found.

By brain scanning human epilepsy patients they found the same post-seizure drop in oxygen supply.

"When a person fits they effectively suffer the same symptoms as though they are having a stroke or transient ischaemic attack - TIA," says Teskey. "And that means that long-term there could be on-going damage occurring in the brain. So this is good reason to try to do something about it."

The good news is that the team are already looking at ways to block the effects in patients.

"Turns out that one of the most effective treatments is ibuprofen [which blocks cyclooxygenase]," says Teskey. "That's what we're going after now..."


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