Delayed anti-nogo-a therapy improves function after chronic stroke in adult rats.

Background And Purpose: we have shown that anti-Nogo-A immunotherapy to neutralize the neurite growth inhibitory protein Nogo-A results in functional improvement and enhanced plasticity after ischemic stroke in the adult rat. The present study investigated whether functional improvement and neuronal plasticity can be induced by this immunotherapy when administered to the chronic stroke-impaired rat.

Methods: adult rats were trained to perform the skilled forelimb reaching test, followed by permanent middle cerebral artery occlusion to impair the preferred forelimb.

Long-term motor improvement after stroke is enhanced by short-term treatment with the alpha-2 antagonist, atipamezole.

Drugs that increase central noradrenergic activity have been shown to enhance the rate of recovery of motor function in pre-clinical models of brain damage. Less is known about whether noradrenergic agents can improve the extent of motor recovery and whether such improvement can be sustained over time. This study was designed to determine if increasing central noradrenergic tone using atipamezole, an alpha-2 adrenoceptor antagonist, could induce a long-term improvement in motor performance in rats subjected to ischemic brain damage caused by permanent middle cerebral artery occlusion.

Motor recovery and axonal plasticity with short-term amphetamine after stroke.

Background And Purpose: There is considerable debate regarding the efficacy of amphetamine to facilitate motor recovery after stroke or experimental brain injury. Different drug dosing and timing schedules and differing physical rehabilitation strategies may contribute to outcome variability. The present study was designed to ascertain (1) whether short-term amphetamine could induce long-term functional motor recovery in rats after an ischemic lesion modeling stroke in humans; (2) how different levels of physical rehabilitation interact with amphetamine to enhance forelimb-related functional outcome; and (3) whether motor improvement was associated with axonal sprouting from intact corticoefferent pathways originating in the contralesional forelimb motor cortex.

Dendritic plasticity in the adult rat following middle cerebral artery occlusion and Nogo-a neutralization.

Our work has shown that following focal ischemic lesion in adult rats, neutralization of the axon growth inhibitor Nogo-A with the monoclonal antibody (mAb) IN-1 results in functional recovery. Furthermore, new axonal connections were formed from the contralesional cortex to subcortical areas corresponding to the observed functional recovery. The present study investigated whether dendritic changes, also known to subserve functional recovery, paralleled the axonal plasticity shown after ischemic lesion and treatment with mAb IN-1.

Functional recovery and neuroanatomical plasticity following middle cerebral artery occlusion and IN-1 antibody treatment in the adult rat.

Stroke is a prevalent and devastating disorder, and no treatment is currently available to restore lost neuronal function after stroke occurs. One unique therapy that may improve functional recovery after stroke is blockade of the neurite inhibitory protein Nogo-A with the monoclonal antibody IN-1, through enhancement of neuroanatomical plasticity from uninjured areas of the central nervous system. In the present study, we combined IN-1 treatment with an ischemic lesion (permanent middle cerebral artery occlusion) to determine the effect of Nogo-A neutralization on cortical plasticity and functional recovery.