Systemic inflammation in spastic forms of cerebral palsy: pathogenetic role and modulation possibilities using Mexidol in motor rehabilitation of pediatric patients

Gaynetdinova D.D.; Afandieva L.Z.

doi:https://doi.org/10.17116/jnevro202612605174

Gaynetdinova D.D.

Kazan State Medical University, Kazan, Russia

ORCID: 0000-0002-4255-9107

Afandieva L.Z.

Kazan State Medical University, Kazan, Russia

ORCID: 0000-0002-8752-4071

Systemic inflammation in spastic forms of cerebral palsy: pathogenetic role and modulation possibilities using Mexidol in motor rehabilitation of pediatric patients

Authors:

Gaynetdinova D.D., Afandieva L.Z.

More about the authors

Journal: S.S. Korsakov Journal of Neurology and Psychiatry. 2026;126(5): 74‑82

DOI: 10.17116/jnevro202612605174

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To cite this article:

Gaynetdinova DD, Afandieva LZ. Systemic inflammation in spastic forms of cerebral palsy: pathogenetic role and modulation possibilities using Mexidol in motor rehabilitation of pediatric patients. S.S. Korsakov Journal of Neurology and Psychiatry. 2026;126(5):74‑82. (In Russ.)
https://doi.org/10.17116/jnevro202612605174

Подписка 2026 Журнал неврологии и психиатрии им. С.С. Корсакова (S.S. Korsakov Journal of Neurology and Psychiatry)

Использование инфографики авторами научных работ

OBJECTIVE

To evaluate the ability of ethylmethylhydroxypyridine succinate (Mexidol) to modulate free radical oxidation rates and pro-inflammatory cytokine activity as a part of comprehensive medical rehabilitation for children diagnosed with spastic cerebral palsy.

MATERIAL AND METHODS

The study cohort included children aged 6 to 8 years with spastic cerebral palsy (CP). Group 1 (n=24) received Mexidol in combination with robotic therapy incorporating biofeedback for 6 weeks. Group 2 (n=23) received only robotic therapy. Assessments were conducted on free radical oxidation indicators, serum levels of pro-inflammatory cytokines (tumor necrosis factor α [TNF-α] and interleukin-6 [IL-6]), and functional cognitive and motor indicators, utilizing data obtained from the integrated sensors of the exoskeleton platform.

RESULTS

In children with spastic forms of cerebral palsy, two concurrent pathogenetic processes were observed: systemic inflammation, indicated by elevated levels of TNF-α and IL-6, and oxidative stress, marked by increased activity of antioxidant defense enzymes (peroxidase, catalase, and superoxide dismutase) alongside indicators of lipid peroxidation (malondialdehyde). The complex therapy demonstrated a statistically significant advantage in improving motor and cognitive indicators compared to robotic therapy only. Specifically, improvements in motor indicators ranged from 37.6% to 58.7%, while cognitive improvements ranged from 14.4% to 52.6%. These enhancements were found to significantly exceed those observed in the group receiving only robotic therapy (motor improvements of 24% to 39% and cognitive improvements of 5% to 22%; intergroup differences p<0.05).

CONCLUSION

The combination therapy in children with spastic cerebral palsy effectively enhances both motor and cognitive functions while modulating antioxidant status and systemic inflammation. The integration of antioxidant pharmacotherapy into rehabilitation programs has been shown to increase the efficacy of training, thereby facilitating the development of a biomarker-driven approach to personalized treatment.

Keywords:

spastic cerebral palsy

robotic therapy

ethylmethylhydroxypyridine succinate

Mexidol

TNF-α

IL-6

free radical oxidation

Authors:

Gaynetdinova D.D.

Kazan State Medical University, Kazan, Russia

ORCID: 0000-0002-4255-9107

Afandieva L.Z.

Kazan State Medical University, Kazan, Russia

ORCID: 0000-0002-8752-4071

Received:

13.04.2026

Accepted:

20.04.2026

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References:

Rosenbaum P, Paneth N, Leviton A, et al. A report: the definition and classification of cerebral palsy. Dev Med Child Neurol. 2007;109:8-14. https://doi.org/10.1111/j.1469-8749.2007.tb12610.x
Gano D, Cowan FM, de Vries LS. Cerebral palsy after very preterm birth an imaging perspective. Semin Fetal Neonatal Med. 2020;25(3):101106. https://doi.org/10.1016/j.siny.2020.101106
Novak I, Morgan C, Adde L. Early, accurate diagnosis and early intervention in cerebral palsy: advances in diagnosis and treatment. JAMA Pediatr. 2017;171(9):877-887. https://doi.org/10.1001/jamapediatrics.2017.1689
Gaynetdinova DD, Yusupova EF. State of lipid peroxidation processes in children with motor disorders in periventricular leukomalacia. Nevrologicheskii Vestnik. 2010;42(3):42-46. (In Russ.).
Gaynetdinova DD, Khakimova RF, Gaysina LZ. Neuroimmunological aspects of cerebral palsy pathogenesis. Meditsinskaya Immunologiya. 2011;13(2-3):115-120. (In Russ.). https://doi.org/10.15789/1563-0625-2011-2-3-115-120
Gaynetdinova DD, Afandiyeva LZ, Khakimova RF. Features of immunological parameters in early age children with spastic forms of cerebral palsy. Ross Vestn Perinatol Pediatr. 2017;62(5):153-157. (In Russ.). https://doi.org/10.21508/1027-4065-2017-62-5-153-157
Magalhães RC, Moreira JM, Lauar AO, et al. Inflammatory biomarkers in children with cerebral palsy: A systematic review. Res Dev Disabil. 2019;95:103508. https://doi.org/10.1016/j.ridd.2019.103508
Sankowski R, Mader S, Valdés-Ferrer SI. Systemic inflammation and the brain: novel roles of genetic, molecular, and environmental cues as drivers of neurodegeneration. Front Cell Neurosci. 2015;9:28. https://doi.org/10.3389/fncel.2015.00028
Volpe JJ, Chappell TM, eds. Volpe’s Neurology of the Newborn. 6th ed. Philadelphia: Elsevier. 2018;1088. ISBN: 978-0-323-47913-4.
Hagberg H, Mallard C, Ferreira AJ. The role of inflammation in perinatal brain injury. Nat Rev Neurol. 2015;11(4):192-208. https://doi.org/10.1038/nrneurol.2015.13
Kuban KC, O’Shea TM, Allred EN, et al; ELGAN Study Investigators. Systemic inflammation and cerebral palsy risk in extremely preterm infants. J Child Neurol. 2014;29(12):1692-1698. https://doi.org/10.1177/0883073813513335
Paton MCB, Finch-Edmondson M, Dale RC, et al. Persistent Inflammation in Cerebral Palsy: Pathogenic Mediator or Comorbidity? A Scoping Review. J Clin Med. 2022;11(24):7368. https://doi.org/10.3390/jcm11247368
Lin CY, Chang YC, Wang ST, et al. Altered inflammatory responses in preterm children with cerebral palsy. Ann Neurol. 2010;68(2):204-212. https://doi.org/10.1002/ana.22049
Zareen Z, Strickland T, Fallah L, et al. Cytokine dysregulation in children with cerebral palsy. Dev Med Child Neurol. 2021;63(4):407-412. https://doi.org/10.1111/dmcn.14770
Afandiyeva LZ, Gaynetdinova DD. Gross motor functions and immune parameters in children with spastic cerebral palsy: is there a connection? Prakticheskaya Meditsina. 2023;21(4):47-54. (In Russ.). https://doi.org/10.32000/2072-1757-2023-4-47-54
Gaynetdinova DD, Semenov VV, Ismagilov MF, Kharitonov VS. Clastogenic, aneugenic, prooxidant and antioxidant properties of some neurotropic drugs. Eksperimental’naya i Klinicheskaya Farmakologiya. 2006;69(3):58-62. (In Russ.).
Jackman M, Sakzewski L, Morgan C, et al. Interventions to improve physical function for children and young people with cerebral palsy: international clinical practice guideline. Dev Med Child Neurol. 2022;64(5):536-549. https://doi.org/10.1111/dmcn.15055
Zavadenko NN, Suvorinova NYu, Batysheva TT, et al. Results of a multicenter double-blind randomized placebo-controlled clinical trial of the efficacy and safety of Mexidol in the treatment of attention deficit hyperactivity disorder in children (MEGA). S.S. Korsakov Journal of Neurology and Psychiatry. 2022;122(4):75-86. (In Russ.). https://doi.org/10.17116/jnevro202212204175
Nemkova SA. Modern approaches to diagnosis and treatment of vegetative dysfunction syndrome in children. S.S. Korsakov Journal of Neurology and Psychiatry. 2024;124(11-2):66-75. (In Russ.). https://doi.org/10.17116/jnevro202412411266
Voronina TA, Litvinova SA, Gladysheva NA, Shulyndin AV. Known and new insights into the mechanism of action and spectrum of effects of Mexidol. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;125(5):22-33. (In Russ.). https://doi.org/10.17116/jnevro202512505122
Shchulkin AV. A modern concept of antihypoxic and antioxidant effects of mexidol. S.S. Korsakov Journal of Neurology and Psychiatry. 2018;118(12-2):87-93. (In Russ.). https://doi.org/10.17116/jnevro201811812287
Carvalho I, Pinto SM, Chagas DV, et al. Robotic gait training for individuals with cerebral palsy: a systematic review and meta-analysis. Arch Phys Med Rehabil. 2017;98(11):2332-2344. https://doi.org/10.1016/j.apmr.2017.03.022
Peake J, Della Gatta P, Suzuki K, et al. Cytokine expression and secretion by skeletal muscle cells: regulatory mechanisms and exercise effects. Exerc Immunol Rev. 2015;21:8-25.
Ertek S, Cicero A. Impact of physical activity on inflammation: effects on cardiovascular disease risk and other inflammatory conditions. Arch Med Sci. 2012;8(5):794-804. https://doi.org/10.5114/aoms.2012.31614
Kalinin SA, Shulgina SM, Antropova EN, et al. State of the human and animal immune system under physical loads of various origins. Immunologiya. 2019;40(3):72-82. (In Russ.). https://doi.org/10.24411/0206-4952-2019-13008
Gray L, Ng H, Bartlett D. The gross motor function classification system: an update on impact and clinical utility. Pediatr Phys Ther. 2010;22(3):315-320. https://doi.org/10.1097/PEP.0b013e3181ea8e52
Vologzhanin DA, Golota AS, Ignatenko AI, et al. Effect of physical activity on the immune system in health and disease: a review. Vestnik Vosstanovitel’noy Meditsiny. 2025;24(1):91-102. (In Russ.). https://doi.org/10.38025/2078-1962-2025-24-1-91-102
Kolesnikova EV, Vyshlova IA, Karpov SM, et al. Cerebral palsy: current status of the problem (review of literature). Russkiy Zhurnal Detskoy Nevrologii. 2024;19(4):20-28. (In Russ.). https://doi.org/10.17650/2073-8803-2024-19-4-20-28
Paul S, Nahar A, Bhagawati M, et al. A review on recent advances of cerebral palsy. Oxid Med Cell Longev. 2022;2022:2622310. https://doi.org/10.1155/2022/2622310
Singh A, Kukreti R, Saso L, et al. Oxidative Stress: A Key Factor in the Pathogenesis of Neurodegenerative Diseases. Molecules. 2019;24(8):1583. https://doi.org/10.3390/molecules24081583
van Kammen K, Boonstra AM, van der Woude LHV, et al. Differences in muscle activity and temporal step parameters between Lokomat guided walking and treadmill walking in post-stroke hemiparetic patients and healthy walkers. J Neuroeng Rehabil. 2017;14:32. https://doi.org/10.1186/s12984-017-0244-z
Than UTT, Nguyen LT, Nguyen PH, et al. Inflammatory mediators drive neuroinflammation in autism spectrum disorder and cerebral palsy. Sci Rep. 2023;13:22587. https://doi.org/10.1038/s41598-023-49902-8
Billiards SS, Haynes RL, Folkerth RD, et al. Myelin abnormalities without oligodendrocyte loss in a neonatal rat model of periventricular leukomalacia. Brain Pathol. 2008;18(2):153-163. https://doi.org/10.1111/j.1750-3639.2007.00107.x
Docherty S, Harley R, McAuley JJ, et al. The effect of exercise on cytokines: implications for musculoskeletal health: a narrative review. BMC Sports Sci Med Rehabil. 2022;14:5. https://doi.org/10.1186/s13102-022-00397-2