Abstract
Background and Purpose: Remote limb ischemic conditioning (RLIC), delivered through brief intermittent bouts of blood pressure cuff inflation on the arm, has recently been shown to have neuroprotective effects. Because the mechanisms through which RLIC promotes tissue protection are multifactorial and epigenetic, RLIC holds promise as a neurorecovery agent to augment learning and optimize rehabilitation outcomes following a stroke. The purposes of this study were to test if RLIC enhanced motor and cognitive learning in human adults compared to a sham treatment and to determine if RLIC at 20 mmHg above systolic blood pressure would yield equivalent results as RLIC to 200 mmHg. Methods: Thirty adults were randomized to three treatment groups (n=10 per group), and participated in a 7 day protocol of RLIC/sham conditioning followed by motor and cognitive training, to induce learning. Learning was assessed at the end of the 7th day and at 2 and 4 week follow-ups. Data were analyzed using repeated measures ANOVAs with planned post-hoc comparisons to analyze group-by-time interaction effects. Results: Despite the same initial motor performance, the two RLIC groups had larger improvements after training at Day 7 compared to the sham group (mean seconds in balance change score ± SEM; RLIC+20: 16.9 ± 1.5 secs; RLIC200: 16.6 ± 1.0 secs; sham: 9.6 ± 1.4 secs; p ≤ .001). Improvements in motor performance in the RLIC groups were retained at 2 week (p = .001) and 4 week (p ≤ .001) follow-ups. There was also a trend towards greater improvements in cognitive performance after training at Day 7 in the two RLIC groups compared to the sham group (mean correct response reaction time change score ± SEM; RLIC+20: -98.4 ± 14.2 ms; RLIC200: -93.0 ± 20.5 ms; sham: -46.6 ± 13.1 ms; p = .074). The two RLIC groups were equivalent at each time point for motor (p = 0.56 - 0.99) and cognitive (p = 0.79 - 0.97) performance. Conclusions: RLIC, induced with cuff inflation as low as 20 mmHg above systolic blood pressure, had a robust effect on both motor and cognitive learning paradigms in healthy adults. RLIC could be a low-cost and clinically-feasible strategy to augment learning and enhance neurorehabilitation following stroke.
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