Prolonged acute intermittent hypoxia improves forelimb reach-to-grasp function in a rat model of chronic cervical spinal cord injury

• Published in: Experimental neurology Vol. 340; p. 113672
• Main Authors: Arnold, Breanna M., Toosi, Behzad M., Caine, Sally, Mitchell, Gordon S., Muir, Gillian D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2021
• Subjects: Chronic spinal cord injury; Intermittent hypoxia; Limb function; Plasticity; Rehabilitation; Task-specific training; Intermittent hypoxia; Task-specific training; Limb function; Rehabilitation; Chronic spinal cord injury; Plasticity
• ISSN: 0014-4886; 1090-2430; 1090-2430
• DOI: 10.1016/j.expneurol.2021.113672

Repetitive acute intermittent hypoxia (AIH – brief, episodes of low inspired oxygen) elicits spinal motor plasticity, resulting in sustained improvements of respiratory and non-respiratory motor function in both animal models and humans with chronic spinal cord injury (SCI). We previously demonstrated that 7 days of AIH combined with task-specific training improves performance on a skilled locomotor task for at least 3 weeks post-treatment in rats with incomplete SCI. Here we investigated the effect of repetitive AIH administered for 12 wks on a forelimb reach-to-grasp task in a rat model of chronic, incomplete cervical SCI. In a replicated, sham-controlled, randomized and blinded study, male Spraque-Dawley rats were subject to partial hemisection at the 3rd cervical spinal segment, and exposed to daily AIH (10, 5 min episodes of 11% inspired O2; 5 min intervals of 21% O2) or sham normoxia (continuous 21% O2) for 7 days beginning 8 weeks post-injury. Treatments were then reduced to 4 daily treatments per week, and continued for 11 weeks. Performance on 2 pre-conditioned motor tasks, single pellet reaching and horizontal ladder walking, was recorded each week for up to 12 weeks after initiating treatment; performance on spontaneous adhesive removal was also tested. SCI significantly impaired reach-to-grasp task performance 8 weeks post-injury (pre-treatment). Daily AIH improved reaching success by the first week of treatment versus sham controls, and this difference was maintained at 12 weeks (p < 0.0001). Daily AIH did not affect step asymmetry or stride length during ladder walking or adhesive removal time. Thus, prolonged AIH combined with task-specific training improved forelimb reach-to-grasp function in rats with a chronic cervical hemisection, but not off-target motor tasks. This study further supports the idea that daily AIH improves limb function when combined with task-specific training. •Cervical spinal hemisection caused persistent reach-to-grasp deficits in rats.•Acute intermittent hypoxia (AIH) and rehabilitative training improved reaching.•Benefits were observed from week 1 after treatment for up to at least 12 weeks.•AIH consistently improved reaching, but recovery time-course varied among.