Stress and corticosterone enhance cognitive recovery from hippocampal stroke in rats

When locally infused, the potent vasoconstrictor, endothelin-1 (ET-1) produces partial ischemic damage in many regions of the brain, including the hippocampus. The hippocampus is known for a high density of glucocorticoid receptors and for the potent actions of stress and corticosterone to modulate function. The current experiment evaluates the effects of stress and corticosterone on the severity of memory impairment and anatomical pathology produced by hippocampal mini-stroke. Rats with ET-1-induced mini-stroke were exposed to mild restraint stress (1 h/day) or oral corticosterone (0.5 mg/kg) for 16 consecutive days. Spatial memory was then tested in the Morris water task (MWT) and the ziggurat task (ZT). The groups ET-1+stress and ET-1+corticosterone performed significantly better in both tasks than the ET-1-only group. This suggests that increasing corticosteroid levels alleviates the hippocampal stroke-induced memory deficits. Hippocampal volumetric assessment also revealed that both the post-stroke stress and corticosteroid treatment significantly decreased the volume of hippocampal damage. The findings support the view that elevated levels of corticosterone may exert neuroprotective effects in the hippocampus following stroke.