Sleep Disturbance Impairs Stroke Recovery in the Rat

Abstract

There is a lack of experimental evidence to support the hypothesis that sleep may modulate stroke outcome as suggested by clinical observations. We have previously shown that sleep disturbance (SDis) over 3 days aggravates brain damage in a rat model of focal cerebral ischemia. The aim of this study is to further investigate effects of SDis on long-term stroke recovery and neuroplasticity as assessed by axonal sprouting, neurogenesis, and angiogenesis. Focal cerebral ischemia was induced by permanent occlusion of the distal branches of middle cerebral artery. Twelve hours after initiation of ischemia, SDis was performed over 3 consecutive days (deprivation of 80% sleep during the 12-h light phase). Weekly assessments on sensorimotor function by the single pellet reaching test (SPR) were performed for 5 weeks after surgery. Axonal sprouting was evaluated by anterograde tracing with biotinylated dextran amine (BDA) and neurogenesis/angiogenesis by bromodeoxyuridine (BrdU) labelling along with cell-type markers. Control groups included ischemia without SDis, sham with SDis, and sham without SDis. Basic sleep research laboratory. Rats subjected to SDis after ischemia showed significantly less recovery of forearm motor skills during the post-stroke period of 5 weeks. This effect was accompanied by a substantial reduction in axonal sprouting, expression of synaptophysin, and the ischemia-stimulated neural and vascular cell proliferation. SDis has detrimental effects on functional and morphological/structural outcomes after stroke, suggesting a role of sleep in the modulation of recovery processes and neuroplasticity.