Delayed recovery and exaggerated infarct size by post-lesion stress in a rat model of focal cerebral stroke

Stress might be one of the most salient intrinsic factors influencing the risk of stroke and its outcome. Previous studies have linked stress to increased infarct size and exaggerated cognitive deficits in rodent models of stroke. This study compares the effects of chronic restraint stress, representing a psychological stressor, prior to or after motor cortex devascularization lesion on motor recovery in rats. Daily testing in a skilled reaching task revealed initially exaggerated deficits in limb use caused by pre-lesion stress in the absence of increased infarct size. Both pre- and post-lesion stresses affected movement by delaying recovery and limiting compensation of lesion-induced deficits. Nevertheless, only rats that experienced post-lesion stress showed enlarged infarct size. This was accompanied by enlarged edema formation in the lesion hemisphere of post-stress animals on day 2 post-lesion. There were no significant differences in infarct size between post-lesion day 2 and day 15. The data demonstrate that both pre- and post-lesion chronic restraint stresses affect motor recovery after ischemic lesion. Lesion volume, however, is influenced by the timing of a stressful experience relative to the lesion. These findings suggest that stress represents a critical variable determining the outcome after stroke. (C) 2008 Elsevier B.V. All rights reserved.