Calming Overexcited Neurons May Protect Brain After Stroke
upstart writes:
New data prompts reconsideration of decades-old theory about brain injury due to stroke:
Neuroscientists believed that, in the aftermath of a stroke, calming overexcited neurons might prevent them from releasing a toxic molecule that can kill neurons already damaged by lack of oxygen. This idea was supported by studies in cells and animals, but it lost favor in the early 2000s after numerous clinical trials failed to improve outcomes for stroke patients.
But a fresh approach has yielded evidence that the idea may have been discarded too hastily. The new findings are available online in the journal Brain.
By scanning the whole genomes of nearly 6,000 people who had experienced strokes, researchers at Washington University School of Medicine in St. Louis identified two genes associated with recovery within the pivotal first 24 hours after stroke. Events -- good or bad -- that occur in the first day set stroke patients on their courses toward long-term recovery. Both genes turned out to be involved in regulating neuronal excitability, providing evidence that overstimulated neurons influence stroke outcomes.
[...] "We started with no hypotheses about the mechanism of neuronal injury," Cruchaga said. "We started with the assumption that some genetic variants are associated with stroke recovery, but which ones they are, we did not guess. We tested every single gene and genetic region. So the fact that an unbiased analysis yielded two genes involved in excitotoxicity tells us that it must be important."
[...] "We know that that first 24-hour period has the greatest impact on outcomes," Lee said. "Beyond 24 hours, there's diminishing returns in terms of influence on long-term recovery. Right now, we don't have any neuroprotective agents for that first 24 hours. Many of the original studies with anti-excitotoxic agents were performed at a time when we weren't sure about the best trial design. We've learned a lot about stroke in the last few decades. I think it's time for a re-examination."
Journal Reference:
Ibanez, Laura, Heitsch, Laura, Carrera, Caty, et al. Multi-ancestry GWAS reveals excitotoxicity associated with outcome after ischaemic stroke, Brain (accepted manuscript)
DOI: 10.1093/brain/awac080
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