Prednisolone Pretreatment Enhances Intermittent Hypoxia-Induced Plasticity in Persons With Chronic Incomplete Spinal Cord Injury

Abstract

Objective. To test the hypothesis that an anti-inflammatory corticosteroid drug enhances spinal motor plasticity induced by acute intermittent hypoxia (AIH) in persons with chronic incomplete spinal cord injury (iSCI). Methods. Fourteen subjects with incomplete spinal cord injury (ASIA level C or D; mean age = 46 years) participated in a randomized, double-blinded, crossover, and placebo-controlled study. Subjects received either 60 mg oral prednisolone or a matching placebo, 1 hour before administration of AIH (15, 60-second hypoxic exposures; fraction of inspired oxygen [FiO2] = 0.09). Changes in voluntary ankle strength, lower extremity electromyograms (EMG), and serum inflammatory biomarkers were quantified. Results. Maximal ankle plantarflexion torque was significantly higher following prednisolone + AIH versus placebo + AIH (mean difference [MD] 9, 11, and 7 newton meter [N∙m] at 30, 60, and 120 minutes post-AIH, respectively; all Ps <.02). Soleus surface EMG during maximal voluntary contraction was also significantly increased following prednisolone + AIH (MD 3.5, P = .02 vs placebo + AIH), while activity of other leg muscles remained unchanged. Individuals had significantly higher levels of the anti-inflammatory serum biomarker interleukin-10 after prednisolone versus placebo ( P = .004 vs placebo + AIH). Conclusions. Pretreatment with prednisolone increased the capacity for AIH-induced functional motor plasticity, suggesting that suppression of inflammation enhances the efficacy of AIH administration in individuals with spinal cord injury. Clinical trial registration number: NCT03752749.