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Investigators at Children's Hospital Boston Discover Method to Stimulate Brain Rewiring after Stroke

June 24, 2002

Researchers at Children's Hospital Boston have used a naturally occurring substance to help stroke-impaired rats 'rewire' their brains and partially recover motor function, according to a study being published in the June 25 issue of the Proceedings of the National Academy of Sciences.

After a stroke, brain cells die and their connections to other parts of the brain are lost. Researchers believe that undamaged brain cells in other brain regions can potentially establish new connections to those areas that have lost their normal inputs, and that this 'rewiring' could result in a limited amount of spontaneous recovery after a stroke.

In the study, inosine was shown to stimulate nerve cells in undamaged parts of the brain to grow new connections into brain areas that had lost their normal connections as a result of a stroke. This 'rewiring' partially compensated for the loss of the original connections, and resulted in significant improvement in several types of behavior compared to rats that did not receive inosine.

'These findings are of both scientific and clinical interest,' said Larry Benowitz, PhD, director of the Laboratories for Neuroscience Research at Children's Hospital Boston, and the principal investigator of the study. 'The study shows that inosine induces a great deal of rewiring in the brain after stroke. This rewiring is apparently sufficient to promote substantial functional recovery. In terms of clinical implications, inosine, which appears to have no apparent side effects in animals thus far, has potential as a novel nerve regeneration approach to treatment of stroke and other types of brain injuries.'

Inosine occurs in low levels in the brain, but in quantities that are insufficient to stimulate significant rewiring after stroke. By providing additional inosine into the brain, nerve cells increase their expression of a set of genes that encode proteins essential for axon growth. In a previous Benowitz lab study, inosine was found to be effective even when administered as much as 24 hours after stroke.

Inosine dramatically improved rats' performance on several behavioral tasks, including reaching for food in a tray outside their cages, placing their paws on a table top as they approached it, and controlling the movement of the paws while swimming. By the fourth week of the study, with their unaffected paw restrained, half of the inosine-treated rats used their stroke-affected paws to reach for food, compared to none of the untreated rats with strokes. Moreover, when inosine-treated rats were allowed to reach with either paw, 20 percent continued to use the paw affected by stroke. This has never been seen after stroke in any previous study, according to collaborating author, Bryan Kolb, Ph.D., an authority on cortical functions in rats, at the University of Lethbridge (Canada). In humans, strokes similar to the ones in the study cause long-lasting, and often permanent losses in movement and sensation.

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Children's Hospital Boston is the nation's premier pediatric medical center. Children's Hospital is the primary pediatric teaching affiliate of Harvard Medical School, home to the world's leading pediatric research enterprise, and the largest provider of health care to the children of Massachusetts. For more information about the hospital visit: www.childrenshospital.org.