Journal of Exercise & Organ Cross Talk
Journal of Eexercise & Organ Cross Talk

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

Document Type : Original Article

Authors

Sahar Seddighi
Foad Feizolahi
Amir Sarshin
Alireza Rahimi

Department of Exercise Physiology, Ka. C., Islamic Azad University, Karaj, Iran.

https://doi.org/10.22122/jeoct.2025.557915.1178
Abstract
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.

What is already known on this subject?

Peripheral nerve injuries (PNIs), particularly those involving the sciatic nerve, represent a significant clinical challenge in neurology and rehabilitation medicine, often leading to long-term sensorimotor deficits, neuropathic pain, and a substantial reduction in quality of life.

 

What this study adds?

The combination strategy (resistance training while lithium), targeting both the extrinsic inhibitory environment and the intrinsic regenerative capacity of the neuron, presents a promising and rational translational approach for the treatment of peripheral nerve injuries

Keywords

Sciatic nerve injury
Neuroinflammation
Lithium
Resistance training
Myeloperoxidase
Nitric oxide

Subjects

Acknowledgements

None

Funding

None

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Compliance with ethical standards

Conflict of interest The authors declare that there is no conflict of interest in the present research.

Ethical approval All procedures were approved by the university ethics committee and complied with institutional guidelines for animal care.

Informed consent Animal study. 

Author contributions 

Conceptualization: S.S., F.F, A.S., A.R., Methodology: S.S., F.F, A.S., A.R., Software: S.S., F.F, A.S., A.R., Validation: S.S., F.F, A.S., A.R.,; Formal analysis: S.S., F.F, A.S., A.R.,; Investigation: S.S., F.F, A.S., A.R.,; Resources: S.S., F.F, A.S., A.R.,; Data curation: S.S., F.F, A.S., A.R.,; Writing - original draft: S.S., F.F, A.S., A.R.,; Writing–review & editing S.S., F.F, A.S., A.R.,; Visualization: S.Sh., H.A, F.Gh., M.GH.,; Supervision: F.F.; Project administration: S.S.,.; Funding acquisition: S.S.    

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Journal of Exercise & Organ Cross Talk
Volume 5, Issue 4
Autumn 2025
Pages 161-167

  • Receive Date 06 September 2025
  • Revise Date 17 November 2025
  • Accept Date 20 November 2025

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