The Effects of Modafinil and Methylprednisolone on Neurological Healing in Experimental Spinal Cord Injury

Year 2026, Volume: 12 Issue: 1, 30 - 48, 25.02.2026

Mehmet Emre Yıldırım , Ayhan Tekiner , Yavuz Erdem , Haydar Çelik , Halil Kul , Adem Kurtuluş , Ömer Şahin , Tuncer Taşcıoğlu , Serdar Cengiz , Kemal Kantarcı , Burak Yürük , Berkay Ayhan , Zeliha Çulcu

https://izlik.org/JA77WP96MZ

Abstract

Objective: Methylprednisolone remains one of the most extensively studied pharmacological agents in the treatment of acute spinal cord injury; however, concerns regarding its adverse effects have prompted the investigation of alternative therapeutic strategies. This study aimed to evaluate the neurobehavioral and electrophysiological effects of Modafinil administered alone and in combination with Methylprednisolone in an experimental rat model of spinal cord injury.
Methods: Twenty-five male Wistar Albino rats were randomly divided into five groups. Following laminectomy and standardized spinal cord trauma, Modafinil and/or Methylprednisolone were administered according to group allocation. Neurobehavioral recovery was assessed using the Inclined Plane Test, and electrophysiological evaluation was performed using motor evoked potential recordings.
Results: A statistically significant difference in inclined plane angles was observed between the groups on postoperative day 1 (p < 0.01). Groups 4 and 5 demonstrated significantly higher functional scores compared to Group 2, whereas no significant difference was observed between Groups 2 and 3. In within-group analysis, functional improvement between day 1 and day 10 was significant in Groups 4 and 5 but not in Groups 1 and 2. Early post-traumatic amplitudes decreased significantly in all trauma groups. Late amplitude measurements demonstrated significant recovery within treatment groups, with greater improvement observed in the combined treatment group.
Conclusion: Modafinil demonstrated beneficial neurobehavioral and electrophysiological effects in this experimental spinal cord injury model. The combined administration of Modafinil and Methylprednisolone resulted in greater functional and electrophysiological recovery, suggesting a potential synergistic effect. Further experimental and clinical studies are required to clarify its therapeutic role.

Keywords

Modafinil , Methylprednisolone , Spinal Cord Injuries , Motor Evoked Potentials

References

• Lu Y, Shang Z, Zhang W, Pang M, Hu X, Dai Y, et al. Global incidence and characteristics of spinal cord injury since 2000–2021: a systematic review and meta-analysis. BMC Med. 2024;22: 285. doi:10.1186/s12916-024-03514-9
• GBD Spinal Cord Injuries Collaborators. Global, regional, and national burden of spinal cord injury, 1990–2019. Lancet Neurol. 2023;22(11): 1026–1047. doi:10.1016/S1474-4422(23)00287-9
• Fischer GF, Bättig L, Stienen MN, Curt A, Fehlings MG, Hejrati N, et al. Advancements in neuroregenerative and neuroprotective therapies for traumatic spinal cord injury. Front Neurosci. 2024;18: 1372920. doi:10.3389/fnins.2024.1372920
• Montoto‑Marqués A, Benito‑Penalva J, Ferreiro‑Velasco ME, Wright MA, Salvador‑De la Barrera S, Kumru H, et al. Advances and new therapies in traumatic spinal cord injury. J Clin Med. 2025;14(7): 2203. doi:10.3390/jcm14072203
• Fehlings MG, Wilson JR, Tetreault LA, Aarabi B, Anderson P, Arnold PM, et al. A clinical practice guideline for the management of acute spinal cord injury: recommendations on the use of methylprednisolone sodium succinate. Global Spine J. 2017;7(3S): 203S–211S. doi:10.1177/2192568217703085
• Evaniew N, Belley‑Côté EP, Fallah N, Noonan VK, Rivers CS, Dvorak MF. Methylprednisolone for the treatment of patients with acute spinal cord injuries: a systematic review and meta-analysis. Global Spine J. 2017;7(3S): 116S–137S. doi:10.1177/2192568217706366
• Geisler FH, Moghaddamjou A, Wilson JRF, Fehlings MG. Methylprednisolone in acute traumatic spinal cord injury: case‑matched outcomes from NASCIS‑II and Sygen historical data. J Neurosurg Spine. 2023;38(5): 595–606. doi:10.3171/2022.12.SPINE22713
• Liu LJW, Rosner J, Cragg JJ. High‑dose methylprednisolone for acute traumatic spinal cord injury: a meta-analysis. Neurology. 2020;95: 272–274. doi:10.1212/WNL.0000000000009263
• Han J, Chen D, Liu D, Zhu Y. Modafinil attenuates inflammation via inhibiting Akt/NF‑κB pathway in apoE‑deficient mouse model of atherosclerosis. Inflammopharmacology. 2018;26(2): 385–393. doi:10.1007/s10787-017-0387-3
• Wadhwa M, Chauhan G, Roy K, Sahu S, Deep S, Jain V, et al. Caffeine and modafinil ameliorate neuroinflammation and anxious behavior during sleep deprivation by inhibiting microglia activation. Front Cell Neurosci. 2018;12: 49. doi:10.3389/fncel.2018.00049
• Brandão WN, Andersen ML, Palermo‑Neto J, Peron JP, Zager A. Therapeutic treatment with modafinil decreases the severity of experimental autoimmune encephalomyelitis in mice. Int Immunopharmacol. 2019;75: 105809. doi:10.1016/j.intimp.2019.105809
• Amini MJ, Seighali N, Bahri RA, Ala M, Jafari RM, Dehpour AR. Repurposing modafinil as an anti‑inflammatory drug: a systematic review of experimental studies. Naunyn Schmiedebergs Arch Pharmacol. 2025;398: 15599–15609. doi:10.1007/s00210-025-03964-9
• Li H, Kim JA, Jo SE, Lee H, Kim KC, Choi S, et al. Modafinil exerts anti‑inflammatory and anti‑fibrotic effects by upregulating adenosine A2A and A2B receptors. Purinergic Signal. 2023. 2024 Aug;20(4): 371-384. doi: 10.1007/s11302-023-09973.
• Visser MM, Goodin P, Parsons MW, Lillicrap T, Spratt NJ, Levi CR, et al. Modafinil treatment modulates functional connectivity in stroke survivors with severe fatigue. Sci Rep. 2019;9: 350. doi:10.1038/s41598-019-46149-0
• Ozturk Y, Bozkurt I, Guvenc Y, Kepoglu U, Cingirt M, Gulbahar O, et al. Modafinil attenuates the neuroinflammatory response after experimental traumatic brain injury. J Neurosurg Sci. 2023;67(4):498–506. doi:10.23736/S0390-5616.21.05382-0
• Rivlin AS, Tator CH. Objective clinical assessment of motor function in rats after experimental spinal cord injury. J Neurosurg. 1977;47: 577–581. doi:10.3171/jns.1977.47.4.0577
• Petersen JA, Spiess M, Curt A, Dietz V, Schubert M. One‑year evolution of motor‑evoked potentials and recovery of leg motor function in 255 patients with acute SCI. Neurorehabil Neural Repair. 2012;26(8): 939–948. doi:10.1177/1545968312438437
• Maeda Y, Takeda M, Mitsuhara T, Okazaki T, Shimizu K, Kuwabara M, et al. Longitudinal electrophysiological changes after mesenchymal stem cell transplantation in a spinal cord injury rat model. PLoS One. 2022;17(8): e0272526. doi:10.1371/journal.pone.0272526
• All AH, Wong KL, Al‑Nashash HA. Characterization of contusive spinal cord injury by monitoring motor‑evoked potentials. Biomedicines. 2024;12(11): 2548. doi:10.3390/biomedicines12112548
• Tekiner AS, Tekiner A, Sargon MF. Effect of propolis on neurological recovery after experimental spinal cord injury. Turk Neurosurg. 2021;31(1): 93–98. doi:10.5137/1019-5149.JTN.29202-20.3