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

Abstract

<i>Objective</i>. 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). <i>Methods</i>. 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 [F_iO₂] = 0.09). Changes in voluntary ankle strength, lower extremity electromyograms (EMG), and serum inflammatory biomarkers were quantified. <i>Results</i>. 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 <i>P</i>s <.02). Soleus surface EMG during maximal voluntary contraction was also significantly increased following prednisolone + AIH (MD 3.5, <i>P</i> = .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 (<i>P</i> = .004 vs placebo + AIH). <i>Conclusions</i>. 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.