Continuous Remote Ischemic Conditioning Attenuates Cognitive and Motor Deficits From Moderate Traumatic Brain Injury

Introduction While studies show that single-dose remote ischemic conditioning (RIC) improves outcomes, the effect of continuous (daily) RIC is unknown. Thus, we aimed to investigate the role of continuous-RIC on cognitive and motor function following traumatic brain injury (TBI). Methods We subjected 24 male C57BL mice to a cortical-controlled TBI. Two-hours after TBI the animals were randomly allocated to the RIC group (n=12) or the Sham group (n=12). RIC was induced by non-invasive external compression of the hind limb using an occlusive band (six 4-min cycles/24 hours) for consecutive 6 days. Before TBI, a baseline rotarod test and novel-object-recognition (NOR) were performed. Post-TBI rotarod and NOR tests were performed on days 1-5, 7, 14, and 21. After the animals were sacrificed on day 21, brain sections were analyzed using Hematoxylin & Eosin (H&E) and Glial Fibrillary Acidic Protein (GFAP) staining to evaluate the hippocampal CA1 area for neuronal injury. Results Both the RIC and Sham groups had lower latency to fall compared to the baseline post-TBI. The RIC animals had a higher latency to fall compared to the Sham animals at all time points, statistically significant after day 3, until day 21 post-TBI. Both the RIC and Sham group had lower recognition index compared to the baseline post-TBI. The RIC animals had a significantly higher recognition index than the Sham animals after day-1, until day 21 post-TBI. H&E and GFAP staining of the brain samples of the Sham group revealed that more neurons in the hippocampal CA1 area appeared shrunken with eosinophilic cytoplasm and pyknotic nuclei compared to the brain samples of the RIC group. Conclusion Post-injury continuous RIC resulted in improved cognitive functions and motor coordination in a mouse model of moderate TBI. Further studies are required to determine optimum dosage and frequency of this novel therapy to maximize its beneficial effects following TBI. Level of Evidence Level 1, Therapeutic studies, randomized controlled trial Oral presentation at the 30th Annual Eastern Association for the Surgery of Trauma, 9th-13th January 2018, Lake Buena Vista, Florida. Address for correspondence: Bellal Joseph, MD, University of Arizona, Department of Surgery, Division of Trauma, Critical Care, and Emergency Surgery. 1501 N. Campbell Ave, Room.5411, P.O. Box 245063, Tucson, AZ 85727, E-mail: bjoseph@surgery.arizona.edu, Tel 520-626-5056, Fax 520-626-5016 © 2018 Lippincott Williams & Wilkins, Inc.

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