Combined lithium and resistance training exerts a synergistic effect on functional recovery and attenuates neuroinflammation in a rat model of sciatic nerve injury

Sciatic nerve injury results in significant functional impairment and is associated with neuroinflammatory responses. While lithium and exercise have shown independent neuroprotective potential, their combined effects remain less explored. This study investigated the therapeutic efficacy of lithium, resistance training, and their combination on functional recovery and neuroinflammatory markers in a rat model of sciatic nerve injury. Twenty-five rats were randomly divided into five groups: Sham, Model (sciatic nerve injury), Model+Lithium, Model+Resistance training, and Model+Lithium+Resistance training. Lithium carbonate (10 mg/kg, i.p.) was administered for 5 days, and resistance training was conducted for 6 weeks, with both interventions starting 24 hours’ post-injury. Functional recovery was assessed using the beam walk test. Neuroinflammation was evaluated by measuring the activity of myeloperoxidase (MPO) and nitric oxide (NO) in the cerebrospinal fluid at the end of the 6-week intervention period. Sciatic nerve injury (Model group) induced a significant deficit in beam test performance compared to the Sham group (p < 0.001). All treatment groups (Lithium, Resistance training, and Combined) showed significant improvement in functional scores compared to the Model group, with the Combined treatment group showing significantly greater recovery than either monotherapy (p < 0.05). Furthermore, the Model group exhibited a significant increase in MPO and NO levels. Resistance training alone and in combination with lithium significantly attenuated this increase (p < 0.0001). Interestingly, lithium monotherapy did not reduce the elevated neuroinflammatory markers. Our findings demonstrate that resistance training alone effectively reduces neuroinflammation and improves functional recovery after sciatic nerve injury. The combination of lithium and resistance training yields a synergistic effect, resulting in the most significant functional improvement, suggesting a promising combined therapeutic strategy for peripheral nerve injury.