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Stanford neuroscientists uncover potential drug treatment for stroke

The third leading cause of death in the United States, stroke is also the number one cause of severe neurological disability, accounting for more than $50 billion annually in related costs. Now, research from Stanford neuroscientists and colleagues offers hope of a potential drug treatment to increase the number of new nerve cells in areas of the brain damaged during stroke and enhance patients' recovery.

In the animal study (subscription required), researchers focused on a compound called LM22A-4, a small molecule whose bulk is less than one-seventieth that of the brain protein it mimics: brain-derived neurotrophic factor (BDNF), a powerful and long-studied nerve growth factor. Critical during the development of the nervous system, BDNF is known to be involved in important brain functions including memory and learning. As my colleague describes in a release:

[The research] team induced severe strokes on one side of the brain in adult laboratory mice that had been previously trained in several distinct athletic tasks. Three days afterward, the researchers administered once-daily intranasal doses of LM22A-4 in a solution to one group of the mice, while giving another group (who had suffered strokes as severe as those in the first group) a similar dose of the same solution without any LM22A-4 in it. Delaying the first dose for three days better tests the ability of this treatment to help stroke patients in the real world, [senior author, Marion Buckwalter, MD, PhD,] said.

Dosing proceeded for 10 weeks, while the scientists monitored both the animals’ recovery of their motor skills and the numbers of new nerve cells in areas of the mice’s brains that had been damaged by strokes.

Mice receiving LM22A-4 regained their athletic prowess considerably more quickly than those given the dummy solution: both the accuracy of their foot placement and the swing speed of the limb on the side of their bodies affected by the stroke improved more rapidly. Moreover, analysis revealed twice as many new nerve cells in these mice’s stroke-affected brain areas, at six and 10 weeks after the event, than in those of their LM22A-4-denied counterparts.

For recovering patients, walking speed is critical, said Buckwalter. “A major factor in their ability to retain their independence and regain their self-confidence lies in their recovering the ability to get around on their feet,” she said.

The results are promising because the compound wasn’t administered to the animals until a full three days after they had suffered strokes, noted Buckwalter. As such, the treatment - if proven effective in humans - could be particularly useful for patients who suffer strokes while sleeping or don't readily recognize the symptoms and don't get to the hospital fast enough for existing therapeutic agents to be administered.

Previously: Brain sponge: Stroke treatment may extend time to prevent brain damage, Every second matters for stroke survival, recovery and Newly approved drug appears to provide more cost-effective stroke prevention than warfarin

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