Abstract

The majority of stroke sufferers need rehabilitation and institutional grade long-term care even after IV-tPA therapy. RIC therapy is easier to perform, safe, promising and ideal for post-stroke rehabilitation. Long-term benefits of RIC have never been reported after eMCAO. Our objective here was to determine if RIC provides long-term behavioral benefits with and without IV-tPA. Methods: eMCAO was induced in WT C57/Bl male mice (~6-mo old). Animals were randomized for the treatments (RIC, NO vs. YES; and IV-tPA, NO vs. YES, n=20/group) after eMCAO. Either IV-tPA (10 mg/kg b.wt.) or IV-saline was infused at 4 hours post-eMCAO. RIC was performed non-invasively on the left hind limb at 2, 8 and 24 hours post-eMCAO, followed by every alternate day till day 15. Neurological deficit score (NDS), and adhesive tape test were performed on day 2, 7 and 15 post-stroke to assess the motor function. Cognitive function was assessed by novel object recognition (NOR) test on day 8 and 16 post-stroke. Results: RIC improved NDS and sensorimotor functions significantly (p<0.05) on day 2 and 7 with and without IV-tPA, but late IV-tPA alone was not effective. On day 15, there was a trend towards improved motor function in RIC treated groups, which was not significant. However, cognitive function was improved significantly (p<0.05) on day 8 and 16 in RIC-treated groups with and without IV-tPA. IV-tPA alone did not provide any significant improvement in cognition. RIC also improved the survival with and without IV-tPA. Conclusion: RIC is a promising therapy for improved motor and cognitive functions during post-stroke rehabilitation and provides survival benefits. Further work is needed to determine the potential of RIC in aged animals and in animals with comorbidities.

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