Sleep disruption aggravates focal cerebral ischemia in the rat.

STUDY OBJECTIVES: Sleep changes are frequent in stroke patients and predict a poor outcome. It remains unclear how sleep influences stroke evolution and recovery. We assessed effects of sleep disruption on brain damage and on the expression of axon sprouting genes after focal cerebral ischemia in rats. DESIGN: 12 h after ischemia induced by occlusion of the middle cerebral artery, rats were subjected to sleep disruption including sleep deprivation for 12h (SDpv12h) and sleep disturbances (SDis) by SDpv12h for consecutive 3 days. Control groups included ischemia without SDpv12h or SDis, sham surgery plus SDis and sham surgery without SDis. Sleep changes were evaluated based on EEG and EMG recordings. MEASUREMENTS AND RESULTS: SDpv12h increased the infarct volume by 40% (SDpv12h 82.8 +/- 10.9 vs. control 59.2 +/- 13.9 mm3, P = 0.008) and SDis by 76% (SDis 58.8 +/- 20.4 vs. control 33.8 +/- 6.3 mm3, P = 0.017). SDpv12h also increased the number of damaged cells, visualized by TUNEL staining, by 137% (SDpv12h 46.8 +/- 15 vs. control 19.7 +/- 7.7/mm2, P < 0.001) and SDis by 219% (SDis 32.9 +/- 13.2 vs. control 10.3 +/- 2.5/mm2, P = 0.002). In addition, SDis significantly elevated the expression of the axonal extension inhibitory molecule neurocan (SDis 14.3 +/- 0.4 vs. control 6.2 +/- 0.1-fold of change, P < 0.001) in the injured hemisphere. CONCLUSIONS: These results provide the first direct evidence for a detrimental impact of sleep disruption on stroke evolution and suggest a potential role of sleep modulating treatments on stroke outcomes.