Identifying Key Targets for Brain Recovery after Stroke

A new study published in Nature offers key insights into a major limitation in the brain’s ability to recover function after a stroke and identifies a promising medical therapy to help overcome this limitation.

Stroke is the leading cause of disability in adults due to the brain’s limited capacity for recovery, and no pharmacological therapy is currently available for promoting recovery. The only option for most patients is physical therapy.

Researchers from UCLA sought to shed some light on the subject by investigating the impact of reducing excessive GABA-mediated tonic inhibition on functional recovery. The brain region adjacent to stroke damage—the peri-infarct zone—is critical for rehabilitation, as it demonstrates “heightened neuroplasticity, allowing sensorimotor functions to re-map from damaged areas. Thus, understanding the neuronal properties constraining this plasticity is important for the development of new treatments,” they hypothesized.

The UCLA researchers found that tonic inhibition immediately after a stroke causes a reduction in the brain’s level of excitability. But while this “damping down” initially helps limit the spread of stroke damage, the increased tonic inhibition level and reduced brain excitability persists for weeks, eventually becoming detrimental to the brain’s recovery, they said.

Based on this finding, the researchers identified a new way to silence this inhibitory response in order to promote stroke recovery and determined the window of time in which this and other brain-repair therapies after stroke should be administered. These findings offer new targets for drug development to promote stroke recovery.

“It was surprising to find that the level of tonic inhibition was increased for so long after stroke and that there was an inflection point where the increased level eventually hindered the brain from recovering,” said Tom Carmichael, MD, PhD, associate professor of neurology at the David Geffen School of Medicine at UCLA and a member of the UCLA Stroke Center, in a press release. “It was also surprising that we could easily manipulate tonic inhibition in the brain after stroke to restore it back to a normal, ‘non-stroke’ level and, in doing this, enhance behavioral recovery.”

For more:

• Reducing excessive GABA-mediated tonic inhibition promotes functional recovery after stroke
• Electrical Brain Stimulation Helps Post Stroke Brain Recover
• Stroke Prevention: Much Can Be Done

What are the possible implications of these results in terms of the potential to more effectively treat patients who suffer a stroke?