PT  - JOURNAL ARTICLE
AU  - Laila Zai
AU  - Christina Ferrari
AU  - Carlie Dice
AU  - Sathish Subbaiah
AU  - Leif A. Havton
AU  - Giovanni Coppola
AU  - Daniel Geschwind
AU  - Nina Irwin
AU  - Eric Huebner
AU  - Stephen M. Strittmatter
AU  - Larry I. Benowitz
TI  - Inosine Augments the Effects of a Nogo Receptor Blocker and of Environmental Enrichment to Restore Skilled Forelimb Use after Stroke
AID  - 10.1523/JNEUROSCI.4498-10.2011
DP  - 2011 Apr 20
TA  - The Journal of Neuroscience
PG  - 5977--5988
VI  - 31
IP  - 16
4099  - http://www.jneurosci.org/content/31/16/5977.short
4100  - http://www.jneurosci.org/content/31/16/5977.full
SO  - J. Neurosci.2011 Apr 20; 31
AB  - Stroke is the leading cause of disability in much of the world, with few treatment options available. Following unilateral stroke in rats, inosine, a naturally occurring purine nucleoside, stimulates the growth of projections from the undamaged hemisphere into denervated areas of the spinal cord and improves skilled use of the impaired forelimb. Inosine augments neurons' intrinsic growth potential by activating Mst3b, a component of the signal transduction pathway through which trophic factors regulate axon outgrowth. The present study investigated whether inosine would complement the effects of treatments that promote plasticity through other mechanisms. Following unilateral stroke in the rat forelimb motor area, inosine combined with NEP1-40, a Nogo receptor antagonist, doubled the number of axon branches extending from neurons in the intact hemisphere into the denervated side of the spinal cord compared with either treatment alone, and restored rats' level of skilled reaching using the impaired forepaw to preoperative levels. Similar functional improvements were seen when inosine was combined with environmental enrichment (EE). The latter effect was associated with changes in gene expression in layer 5 pyramidal neurons of the undamaged cortex well beyond those seen with inosine or EE alone. Inosine is now in clinical trials for other indications, making it an attractive candidate for the treatment of stroke patients.