An Exercise Mimetic Approach to Reduce Poststroke Deconditioning and Enhance Stroke Recovery.

Evidence supports early rehabilitation after stroke to limit disability. However, stroke survivors are typically sedentary and experience significant cardiovascular and muscular deconditioning. Despite growing consensus that preclinical and clinical stroke recovery research should be aligned, there have been few attempts to incorporate cardiovascular and skeletal muscle deconditioning into animal models of stroke. Here, we demonstrate in rats that a hindlimb sensorimotor cortex stroke results in both cardiovascular and skeletal muscle deconditioning and impairments in gait akin to those observed in humans. To reduce poststroke behavioral, cardiovascular, and skeletal muscle perturbations, we then used a combinatorial intervention consisting of aerobic and resistance exercise in conjunction with administration of resveratrol (RESV), a drug with exercise mimetic properties. A combination of aerobic and resistance exercise mitigated decreases in cardiovascular fitness and attenuated skeletal muscle abnormalities. RESV, beginning 24 hours poststroke, reduced acute hindlimb impairments, improved recovery in hindlimb function, increased vascular density in the perilesional cortex, and attenuated skeletal muscle fiber changes. Early RESV treatment and aerobic and resistance exercise independently provided poststroke benefits, at a time when individuals are rapidly becoming deconditioned as a result of inactivity. Although no additive effects were observed in these experiments, this approach represents a promising strategy to reduce poststroke behavioral impairments and minimize deconditioning. As such, this treatment regime has potential for enabling patients to engage in more intensive rehabilitation at an earlier time following stroke when mechanisms of neuroplasticity are most prevalent.

An RFID-based activity tracking system to monitor individual rodent behavior in environmental enrichment: Implications for post-stroke cognitive recovery.

BACKGROUND: Diminished cognitive flexibility is a common form of executive dysfunction that results from stroke in the prefrontal cortex. Potential therapies targeting this type of cognitive deficit following stroke are lacking. NEW METHOD: Here, we used environmental enrichment (EE) as a rehabilitation approach, integrated with a radio frequency identification (RFID)-based activity tracking system to evaluate the contribution of individual EE elements to promote cognitive recovery. Male and female Sprague-Dawley rats received either sham surgery or endothelin-1 (ET-1) induced focal ischemia targeting the medial prefrontal cortex (mPFC). Cognitive flexibility was assessed through an egocentric-spatial version of the Morris Water Maze (MWM) task. RESULTS: Prefrontal cortex damage resulted in impaired reversal learning using the egocentric MWM and reduced physical activity in the running wheel, while social interaction was not affected. EE exposure (2 h/day, 5 days/week, for 5 weeks) improved cognitive flexibility in reversal learning of egocentric MWM for both stroke and sham rats. COMPARISON WITH EXISTING METHOD: As changes in cognition post-stroke can be subtle and difficult to detect using conventional behavioural assessment, we suggest that the implementation of individualized automated animal tracking as used herein will ultimately help decipher whether individual components of EE are important for promoting cognitive recovery post-stroke. CONCLUSION: This study represents an attempt to better align preclinical and clinical implementations of EE and facilitate the uptake of this intervention in the clinical setting.