AbstractIntroductionSpinal cord injury (SCI) leads to inflammation, axonal degeneration, and gliosis. A combined treatment of exercise and neural stem cells (NSC) has been proposed to improve neural repair. This study evaluated a combined treatment of high‐intensity interval training (HIIT) with NSC generation from adipose‐derived stem cells (ADSCs) on a contusive model of SCI in rats.Materials and MethodsIn vitro, rat ADSCs were isolated from the perinephric regions of Sprague–Dawley rats using enzymatic digestion. The ADSCs were transdifferentiated into neurospheres using B27, EGF, and bFGF. After production of NSC, they were labeled using green fluorescent protein (GFP). For the in vivo study, rats were divided into eight groups: control group, sham operation group, sham operation + HIIT group, sham operation + NSC group, SCI group, SCI + HIIT group, SCI + NSC group, and SCI/HIIT/NSC group. Laminectomy was carried out at the T12 level using the impactor system. HIIT was performed three times per week. To assess behavioral function, the Basso–Beattie–Bresnahan (BBB) locomotor test and H‐reflex was carried out once a week for 12 weeks. We examined glial fibrillary acidic protein (GFAP), S100β, and NF200 expression.ResultsNSC transplantation, HIIT and combined therapy with NSC transplantation, and the HIIT protocol improved locomotor function with decreased maximum H to maximum M reflexes (H/M ratio) and increased the Basso–Beattie–Bresnahan score.ConclusionCombined therapy in contused rats using the HIIT protocol and neurosphere‐derived NSC transplantation improves functional and histological outcomes.