The Effects of Pharmacotherapy and Training on Functional Recovery after Global and Focal Cerebral Ischemia in Rats

The brain is an organ which is constantly modulated by our experiences. Moreover, the brain is capable of reorganization following injuries, such as stroke. There is evidence that adaptive reorganization can be supported by rehabilitative training and pharmacotherapy. We investigated the recovery promoting significance of two catecholaminergic agents: an α2-adrenoceptor antagonist, atipamezole, and a monoamine oxidase type-B (MAO-B) inhibitor, selegiline, in experimental models of focal and global cerebral ischemia. We also studied the efficacy of spontaneous training in an enriched environment in these two stroke models. The outcome of these treatments was assessed by different behavioural tests. The effect of housing in an enriched environment on hippocampal function was studied by Fos-staining following a learning experience in a water-maze test. We found that atipamezole treatment facilitated recovery following focal cerebral ischemia in sensorimotor tests. However, it is not clear whether atipamezole treatment actually enhanced the recovery or only hastened it, since ischemic animals eventually reached the same performance level as the drug treated rats. Selegiline treatment was found to attenuate the cognitive deficit following focal cerebral ischemia, but this effect was dependent upon concomitant rehabilitative training. The rehabilitative training with an enriched-environment housing facilitated the recovery from a spatial learning deficit and abolished the hyperactivity following global cerebral ischemia. When assessed after a learning situation the enrichedenvironment housing increased the activation of hippocampus in the dentate gyrus revealed by activation of Fos-positive neurons in sham-operated rats and in their counterparts subjected to global ischemia. In conclusion, recent evidence has shown that atipamezole and selegiline can both be considered as good candidates for recovery promoting agents following stroke. Furthermore, these data show that rehabilitative training also plays an important role in the recovery and may even be necessary if one is to achieve the recovery promoting pharmacologic effects. National Library of Medicine Classification: WL 355, QY 58 Medical Subject Headings: brain ischemia; ischemic attack, transient; brain/drug effects; environment; housing, animal; motor activity/drug effects; maze learning; adrenergic alpha-antagonists; receptors, adrenergic, alpha-2; selegiline; rats; animal