Jun 24, 2002
By Megan Rauscher
NEW YORK (Reuters Health)
In adult rats with unilateral cortical infarcts, treatment with inosine, a naturally occurring substance, stimulated undamaged neurons to form new connections into damaged areas of the midbrain and spinal cord, resulting in markedly improved recovery.
"We hope that this can be translated clinically into a treatment that might help improve level of recovery after stroke in humans," Dr. Larry I. Benowitz of Children's Hospital in Boston said in a telephone interview with Reuters Health. He and colleagues from Boston Life Sciences, Inc and elsewhere describe their studies in the June 25th Proceedings of the National Academy of Sciences.
Naturally occurring concentrations of inosine in the brain are insufficient to induce significant rewiring after stroke, according to the team. Artificially increasing inosine levels leads to increased neuronal expression of genes that encode proteins required for axon growth.
After experimentally induced stroke, rats treated with inosine showed dramatic improvement on several behavioral tasks compared with saline-treated rats. On tests like reaching through bars to retrieve food there is a "black-and-white difference," Dr. Benowitz said.
By week 4, when the unaffected paw was restrained, 50% of inosine-treated rats used their affected paw to reach for food compared with none of the untreated rats. When inosine-treated rats were allowed to reach with either paw, 20% used the affected paw, a result never seen before, according to Canadian scientist and collaborator Dr. Bryan Kolb of the University of Lethbridge.
Behavioral results correlated with anatomical study results. "Normally after stroke there is limited recovery and this is generally thought to be due to some compensation by remaining intact parts of the brain, including, perhaps, some degree of anatomical rewiring," Dr. Benowitz explained. "But this rewiring is presumed to be at a very modest level. What we think inosine does is amplify that rewiring several-fold, and, accordingly, the recovery is very noticeably better."
Clinical trials, spearheaded by Boston Life Sciences, are expected to begin in the next few months.
Proc Natl Acad Sci USA 2002;99:9031-9036.
© 2002 Reuters Ltd