Remote limb ischemic conditioning to enhance neuroplasticity and learning.

Research Report
Population: Adult

Kendra M. Cherry-Allen, PT, DPT, PhD, Doctoral Candidate in the Movement Science Program, Washington University in St. Louis School of Medicine

Jeff Gidday, PhD, Associate Professor in Neurological Surgery, Cell Biology and Physiology, & Ophthalmology and Visual Sciences, Washington University in St. Louis School of Medicine
current address :Department of Ophthalmology, Louisiana State University School of Medicine, LSU Health Sciences Center, New Orleans, LA 70112

Jin-Moo Lee, MD, PhD, Professor in Neurology, Washington University in St. Louis School of Medicine

Tamara Hershey, PhD, Professor in Neurology, Psychiatry, & Radiology, Washington University in St. Louis School of Medicine

Catherine Lang, PT, PhD, Associate Professor in Physical Therapy, Neurology, & Occupational Therapy, Washington University in St. Louis School of Medicine

Keywords: Plasticity, Remote Limb Ischemic Conditioning, Motor learning, Behavioral Training


Purpose: Conditioning one tissue with sub-injurious bouts of ischemia induces protection of remote tissues against subsequent ischemic challenges (remote ischemic conditioning). Inducing remote limb ischemic conditioning (RLIC) with a blood pressure cuff has both cardio- and neuroprotective effects. The mechanisms of RLIC are multifactorial and epigenetic, and may potentially be harnessed for the purposes of neuroplasticity.

Experiment 1 tested if conditioning the nervous system with RLIC prior to training would facilitate the neurophysiological processes of learning, making training more effective in neurologically-intact adults.  We hypothesized that improvements in motor and cognitive performance would be greater in those who received RLIC vs. sham conditioning. Experiment 2 optimized RLIC parameters in neurologically-intact adults by assessing RLIC at two different pressures, with the goal of reducing side effects of bruising.  We hypothesized that the benefits of RLIC could be reproduced with more tolerable cuff inflation pressures.

Number of Subjects: Experiment 1: 18; Experiment 2: 30

Materials/Methods: Experiments 1 and 2 were 9 sessions and single-blinded. Sessions one and two consisted of RLIC/sham conditioning, achieved via blood pressure cuff on the non-dominant arm. Following two sessions of conditioning alone, subjects returned for 5 consecutive conditioning + training sessions. During each of these sessions, subjects underwent RLIC/sham conditioning followed by 15 minutes of motor training on balance task and 15 minutes of cognitive training on an associative recognition task. Posttest performance was assessed at the end of the fifth conditioning + training session and at two follow-up visits 2 and 4 weeks later. In an attempt to elucidate underlying mechanisms we included measures of muscle activation, muscle strength, and serum BDNF concentration in Experiment 1, and serum markers of ischemia in the hemostatic, inflammatory, and endothelial pathways in Experiment 2.

Results: Experiment 1: Using repeated measures ANOVAs, we found that subjects who received RLIC had significantly greater improvements on the balance task and retention of those improvements compared to subjects who received sham conditioning. Compared to sham conditioning, RLIC did not result in greater improvements in cognitive performance or retention, nor was it associated with increases in muscle activation, muscle strength, or serum BDNF concentration. Experiment 2 results are pending.

Conclusions: RLIC has a robust effect on motor learning and retention in neurologically-intact adults. The results of Experiment 2 will allow us to optimize conditioning parameters so that RLIC could be implemented in persons with motor deficits post-stroke to improve rehabilitation outcomes.

Clinical Relevance:  RLIC induced via a blood pressure cuff could be a low-tech, low-cost, and clinically-feasible strategy to maximize experience-dependent plasticity and enhance neurorehabilitation training.

Cherry-Allen, Kendra M., PT, DPT, PhD; Gidday, Jeff M., PhD; Lee, Jin-Moo , MD, PhD; Hershey, Tamara , PhD; Lang, Catherine E., PT, PhD. Remote limb ischemic conditioning to enhance neuroplasticity and learning.. Poster Presentation. IV STEP Conference, American Physical Therapy Association, Columbus, OH, July 17, 2016. Online.