Lost brain function can be restored after stroke

Researchers have succeeded in restoring lost brain function in mouse models of stroke using small molecules, which could in future be developed into a stroke recovery therapy. Their breakthrough has been published in the journal Brain.

In an ischemic stroke, lack of blood flow to the brain causes damage, which rapidly leads to nerve cell loss that affects the network of nerve cells in the brain. This may lead to paralysis, sensorimotor impairment, and vision and speech difficulties, as well as pain and depression.

There are currently no approved drugs that improve or restore these functions after a stroke, apart from clot-dissolving treatment in the acute phase (within 4.5 hours of the stroke). Some spontaneous improvements occur, but many stroke patients suffer chronic loss of function. For example, about 60% of stroke sufferers experience lost somatosensory functions such as touch and position sense.

The new study, led by Lund University in collaboration with University of Rome La Sapeinza and Washington University in St. Louis, shows promising results in mice and rats that were treated with a class of substances that inhibit the metabotropic glutamate receptor (mGluR5), a receptor that regulates communication in the brain’s nerve cell network. As explained by study leader Tadeusz Wieloch, from Lund University, “Rodents treated with the GluR5 inhibitor regained their somatosensory functions.”

Two days after the stroke, ie, when the damage had developed and function impairment was most prominent, the researchers started treating the rodents that exhibited the greatest impaired function. According to Wieloch, “A temporary treatment effect was seen after just 30 minutes, but treatment for several weeks is needed to achieve a permanent recovery effect. Some function improvement was observed even when the treatment started 10 days after a stroke.”

Importantly, sensorimotor functions improved, even though the extent of the brain damage was not diminished. Wieloch said this is due to the intricate network of nerve cells in the brain, known as the connectome, ie, how various areas of the brain are connected and communicate with each to form the basis for various brain functions. Sensorimotor function was further improved if treatment with the mGluR5 inhibitor is combined with somatosensory training by housing several rodents in cages enriched with toys, chains, grids and plastic tubes.

“Impaired function after a stroke is due to cell loss, but also because of reduced activity in large parts of the connectome in the undamaged brain,” Wieloch said. “The receptor mGluR5 is apparently an important factor in the reduced activity in the connectome, which is prevented by the inhibitor which therefore restores the lost brain function.”

The researchers hope their work could lead to a clinical treatment that could be initiated a few days after an ischemic stroke, so long as they are able to repeat their results in humans. According to Wieloch, “This should be possible since several mGluR5 inhibitors have been studied in humans for the treatment of neurological diseases other than stroke, and shown to be tolerated by humans.”

Image credit: iStock.com/Renata Angerami