Stress precipitates functional deficits following striatal silent stroke: a synergistic effect

Stress has been linked to structural and functional outcomes after stroke. Moreover, the striatum, both dorsal and ventral, is a vital regulator of stress perception and associated physiological responses. This study investigates potential synergistic effects of focal stroke in the ventrolateral striatum and restraint stress on motor and spatial performance. Adult male Long-Evans rats were pre-trained in a skilled reaching task and randomly assigned to sham, stroke-only, stress-only and stroke+stress conditions. Ventrolateral striatal focal ischemia was induced by endothelin-1 (ET-1) infusion. Rats in stress-only and stroke+stress groups received 21 days of mild restraint stress after stroke. All rats were tested in the skilled reaching task and the ziggurat task (ZT) for post-stroke motor and spatial performance. There was no effect of ventrolateral striatal ischemia or stress alone on motor and spatial performance. Notably, stroke and stress interacted synergistically to reduce reaching success and to disrupt qualitative aspects of movement performance in the absence of histological differences in lesion size. Thus, stress can precipitate behavioural deficits after focal ischemia even in the absence of significant functional deficits on its own. These results emphasize the importance of prevention programmes to control post-stroke levels of stress in clinical populations.