Abstract TMP65: Remote Ischemic Conditioning With Exercise (RICE) Induced Better Neurorehabilitation After Ischemic Stroke

• Published in: Stroke (1970) 2022-02, Vol.53 (Suppl_1), p.ATMP65-ATMP65
• Main Authors: Wang, Qingzhu, Geng, Xiaokun, Wills, Melissa, Li, Fengwu, Ding, Yuchuan
• Format: Article
• Language: English
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/str.53.suppl_1.TMP65

ObjectiveAlthough early performance is well recognized as an important concept in rehabilitation, the optimal models remain to be determined. Physical exercise has long been considered a promising strategy at the forefront of stroke rehabilitation. However, very early exercise has been demonstrated to exacerbate brain injury. Remote ischemic conditioning (RIC) is safe and feasible within 24 hours after stroke, while it has not been applied to post-stroke rehabilitation. The present study was to establish a novel rehabilitation strategy, the RIC followed by exercise (RICE). MethodsA total of 32 adult male Sprague-Dawley rats were used in 4 groups1) stroke, 2) stroke with exercise (exercise at day 5 and up to day 28), 3) stroke with RIC (RIC at 6 hours after reperfusion and up to day 28), and 4) stroke with RICE (initiated with RIC at 6 hours after reperfusion followed by exercise at day 5 and up to day 28). Long-term functional outcomes were determined by grid walk tests, rota-rod tests, beam balance tests, forelimb placing tests, and the Morris water maze. Synaptogenesis [synaptophysin (SYN), and post-synaptic density protein-95 (PSD-95)], angiogenesis [vascular endothelial growth factor (VEGF), Angiopoietin-1 (Ang-1), and Angiopoietin-2 (Ang-2)], and regulatory molecules [brain-derived neutrophic factor (BDNF), hypoxia inducible factor 1α (HIF-1α), phospholipase D2 (PLD2) and mechanistic target of rapamycin (mTOR) pathway] were all measured at the mRNA and protein levels with real-time PCR and Western blot. ResultsAlthough all rehab procedures induced significant improvement in functional outcomes, including in sensory, motor, and cognitive functions, RICE but not RIC and exercise alone was better able to improve functions after stroke. The functional improvement was significantly associated with gene and protein expressions of molecules for neuroplasticity, synaptogenesis and angiogenesis, with additional increases being induced by RICE. A HIF-1α/PLD2/mTOR signaling pathway was underpinning this processes. ConclusionsRICE induced a better rehabilitation after ischemic stroke by promoting neuroplasticity. This study established the RICE strategy and provided novel clues to pave future endeavors in stroke rehabilitation.