Abstract
Purpose: The mechanism underlying forced limb-use -induced structural plasticity remains to be studied. We examined whether the cyclic adenosine monophosphate (cAMP)–mediated signal transduction pathway was involved in brain plasticity and promoted behavioral recovery induced by forced limb-use after stroke. Methods: Adult rats were divided into a sham group, an ischemia group, an ischemia group with forced limb-use, and an ischemia group with forced limb-use and infusion of N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoline-sulfonamide (H89). Forced limb-use began on post-stroke day 7. Biotinylated dextran amine (BDA) was injected into the sensorimotor cortex on post-stroke day 14. Behavioral recovery was evaluated on post-stroke days 29 to 32, and the levels of cAMP, PKA C-α, phosphorylated CREB (pCREB), synaptophysin, PSD-95, BDA, and BrdU/NeuN were measured. Results: The number of midline-crossing axons and the expression levels of synaptophysin and PSD-95 were increased after forced limb-use. Forced limb-use enhanced the survival of the newborn neurons and increased the levels of cAMP, PKA C-α and pCREB. These were significantly suppressed by H89. Behavioral performance improved with forced limb-use and was reversed with H89. Conclusions: Enhanced structural plasticity and the behavioral recovery promoted by post-stroke forced limb-use are suggested to be mediated through the cAMP/PKA/CREB signal transduction pathway.
Get full access to this article
View all access options for this article.