Stroke drug cocktail normalizes brain fluids, restores movement in mice

Adrenergic receptor (AdR) antagonists work by counteracting electrical and chemical disturbances in the brain. New research in mouse models suggests that a cocktail of these drugs may reduce the spread of tissue damage and aid in recovery.

Researchers led by the Riken Center for Brain Science in Japan administered AdR blockers to mice following a stroke and observed fluid in the brain, which can accumulate and lead to damaging swelling. They discovered that the drugs normalized fluid exchange and helped level out potassium in the animals’ brains.

Mice that received the drugs were able to regain the use of their front legs more quickly than animals that were not treated, the researchers reported in the journal Proceedings of the National Academy of Sciences.

"We know that the water dynamics in the brain immediately during and after a stroke are critical, so we focused on the pathways that move fluids in and out of cells," said lead author Hiromu Monai in a statement.

Specifically, they zeroed in on a fluid channel called aquaporin-4, the levels of which fall following a stroke. They hypothesized that aquaporin-4 is critical to protecting the brain during a stroke. To prove it, they took mice that had been genetically engineered to lack the fluid channel and treated them with AdR blockers. Their brain potassium levels stayed high, and they showed no benefits from the treatment, the team reported.

Several research groups are exploring different strategies for reducing brain swelling after a stroke. Last year, for example, a team at the Medical University of South Carolina described a compound that tamped down the immune response to stroke in mice, lowering inflammation in their brains without negatively affecting immune functions throughout the rest of the body.

Biogen bet $335 million last year on TMS’ plasminogen activator, which breaks down blood clots after strokes and inhibits inflammation in the brain.

The Riken researchers have applied for a patent for their AdR treatment, they said. "Keeping potassium levels in balance is an alternative therapeutic strategy for stroke, and we found that adrenergic receptor blockers promote this normalization," Monai said.

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