Особенности цитокинового статуса в патогенезе детского церебрального паралича и возможности физической реабилитации
https://doi.org/10.18699/SSMJ20250406
Аннотация
Детский церебральный паралич (ДЦП) является одной из ведущих причин инвалидизации в детском возрасте. В ряде случаев данная патология существенно снижает качество жизни пациентов и требует комплексного междисциплинарного подхода к лечению, поэтому крайне актуальны задачи ранней диагностики, профилактики и коррекции ее осложнений. Для разработки эффективных стратегий лечения необходимо понимать не только этиологические факторы, но и патогенетические механизмы, лежащие в основе заболевания. Последнее время особая роль уделяется проблеме персистирующего воспаления в результате активации микроглии у пациентов с ДЦП после органического повреждения мозга. Все больше данных свидетельствует о том, что дисбаланс прои противовоспалительных цитокинов в головном мозге усугубляет нейрональное повреждение и ухудшает реабилитационный прогноз. Дальнейшие исследования нейровоспаления необходимы для выявления ключевых мишеней и разработки новых подходов физической реабилитации пациентов с ДЦП. Цель данного обзора – представить современные данные по проблеме нейровоспаления у пациентов с ДЦП и возможные точки воздействия методами физической реабилитации.
Об авторе
Т. Н. Щербинина
НИИ детской курортологии, физиотерапии и медицинской реабилитации
Россия
Россия
Щербинина Татьяна Николаевна
297412, г. Евпатория, ул. Маяковского, 6
Список литературы
1. Graham H.K., Rosenbaum P., Paneth N., Dan B., Lin J.P., Damiano D.L., Becher J.G., GaeblerSpira D., Colver A., Reddihough D.S., Crompton K.E., Lieber R.L. Cerebral palsy. Nat. Rev. Dis. Primers. 2016;2(1):15082. doi: 10.1038/nrdp.2015.82
2. Sadowska M., Sarecka-Hujar B., Kopyta I. Cerebral palsy: current opinions on definition, epidemiology, risk factors, classification and treatment options. Neuropsychiatr. Dis. Treat. 2020;16:1505–1518. doi: 10.2147/NDT.S235165
3. Novak I., Morgan C., Adde L., Blackman J., Boyd R.N., Brunstrom-Hernandez J., Cioni G., Damiano D., Darrah J., Eliasson A.C., … Badawi N. Early, accurate diagnosis and early intervention in cerebral palsy: advances in diagnosis and treatment. JAMA Pediatrics. 2017;171(9):897–907. doi: 10.1001/jamapediatrics.2017.1689
4. Kołtuniuk A., Rozensztrauch A., Budzińska P., Rosińczuk J. The quality of life of Polish children with cerebral palsy and the impact of the disease on the family functioning. J. Pediatr. Nurs. 2019;47:75–82. doi: 10.1016/j.pedn.2019.05.011
5. Vitrikas K., Dalton H., Breish D. Cerebral palsy: an overview. Am. Fam. Physician. 2020;101(4):213–220.
6. Paton M.C., Finch-Edmondson M., Dale R.C., Fahey M.C., Nold-Petry C.A., Nold M.F., Griffin A.R., Novak I. Persistent inflammation in cerebral palsy: pathogenic mediator or comorbidity? A scoping review. J. Clin. Med. 2022;11(24):7368. doi: 10.3390/jcm11247368
7. Than U.T., Nguyen L.T., Nguyen P.H., Nguyen X.H., Trinh D.P., Hoang D.H., Nguyen P.A., Dang V.D. Inflammatory mediators drive neuroinflammation in autism spectrum disorder and cerebral palsy. Sci. Rep. 2023;13(1):22587. doi: 10.1038/s41598-023-49902-8
8. Schleiss M.R. Altered cytokine responses in children with cerebral palsy: pathogenesis and novel therapies. Dev. Med. Child. Neurol. 2021;63(4):365–366. doi: 10.1111/dmcn.14821
9. Page M.J., McKenzie J.E., Bossuyt P.M., Boutron I., Hoffmann T.C., Mulrow C.D., Shamseer L., Tetzlaff J.M., Akl E.A., Brennan S.E., … Moher D. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:71. doi: 10.1136/bmj.n71
10. Yi M., Li T., Niu M., Zhang H., Wu Y., Wu K., Dai Z. Targeting cytokine and chemokine signaling pathways for cancer therapy. Signal Transduct. Target. Ther. 2024;9(1):176. doi: 10.1038/s41392-024-01868-3
11. Sochocka M., Diniz B.S., Leszek J. Inflammatory response in the CNS: friend or foe? Mol. Neurobiol. 2017;54(10):8071–8089. doi: 10.1007/s12035-016-0297-1
12. Mallah K., Couch C., Borucki D.M., Toutonji A., Alshareef M., Tomlinson S. Anti-inflammatory and neuroprotective agents in clinical trials for CNS disease and injury: where do we go from here? Front. Immunol. 2020;11:2021. doi: 10.3389/fimmu.2020.02021
13. Bourgognon J.M., Cavanagh J. The role of cytokines in modulating learning and memory and brain plasticity. Brain Neurosci. Adv. 2020;4:2398212820979802. doi: 10.1177/2398212820979802
14. Kummer K.K., Zeidler M., Kalpachidou T., Kress M. Role of IL-6 in the regulation of neuronal development, survival and function. Cytokine. 2021;144:155582. doi: 10.1016/j.cyto.2021.155582
15. Kerkis I., da Silva Á.P., Araldi R.P. The impact of interleukin-6 (IL-6) and mesenchymal stem cell-derived IL-6 on neurological conditions. Front. Immunol. 2024;15:1400533. doi: 10.3389/fimmu.2024.1400533
16. Belizário J.E., Fontes-Oliveira C.C., Borges J.P., Kashiabara J.A., Vannier E. Skeletal muscle wasting and renewal: a pivotal role of myokine IL-6. Springerplus. 2016;5:619. doi: 10.1186/s40064-016-2197-2
17. Ramesh G., MacLean A.G., Philipp M.T. Cytokines and chemokines at the crossroads of neuroinflammation, neurodegeneration, and neuropathic pain. Mediators Inflamm. 2013;2013:480739. doi: 10.1155/2013/480739
18. Wu J., Li X. Plasma tumor necrosis factor-alpha (TNF-α) levels correlate with disease severity in spastic diplegia, triplegia, and quadriplegia in children with cerebral palsy. Med. Sci. Monit. 2015;21:3868–3874. doi: 10.12659/msm.895400
19. Bi D., Chen M., Zhang X., Wang H., Xia L., Shang Q., Li T., Zhu D., Blomgren K., He L., … Zhu C. The association between sex-related interleukin-6 gene polymorphisms and the risk for cerebral palsy. J. Neuroinflammation. 2014;11:100. doi: 10.1186/1742-2094-11-100
20. Pingel J., Barber L., Andersen I.T., Walden F.V., Wong C., Døssing S., Nielsen J.B. Systemic inflammatory markers in individuals with cerebral palsy. European Journal of Inflammation. 2019;17:205873921882347. doi: 10.1177/2058739218823474
21. Hu M., Bai C., Zhao H., Wu J., Luan X. Research progress on the role of the interleukin family in the pathogenesis of cerebral palsy in children. J. Integr. Neurosci. 2024;23(12):213. doi: 10.31083/j.jin2312213
22. Mallick R., Basak S., Chowdhury P., Bhowmik P., Das R.K., Banerjee A., Paul S., Pathak S., Duttaroy A.K. Targeting cytokine-mediated inflammation in brain disorders: developing new treatment strategies. Pharmaceuticals (Basel). 2025;18(1):104. doi: 10.3390/ph18010104
23. Bessis A., Béchade C., Bernard D., Roumier A. Microglial control of neuronal death and synaptic properties. Glia. 2007;55(3):233–238. doi: 10.1002/glia.20459
24. Teo E.J., Chand K.K., Miller S.M., Wixey J.A., Colditz P.B., Bjorkman S.T. Early evolution of glial morphology and inflammatory cytokines following hypoxic-ischemic injury in the newborn piglet brain. Sci. Rep. 2023;13(1):282. doi: 10.1038/s41598-022-27034-9
25. Zheng Y., Zhu T., Chen B., Fang Y., Wu Y., Feng X., Pang M., Wang H., Zhu J., Lin Z. Diallyl disulfide attenuates pyroptosis via NLRP3/Caspase-1/ IL-1β signaling pathway to exert a protective effect on hypoxic-ischemic brain damage in neonatal rats. Int. Immunopharmacol. 2023;124(Pt B):111030. doi: 10.1016/j.intimp.2023.111030
26. Schafer D.P., Stevens B. Microglia function in central nervous system development and plasticity. Cold Spring Harb. Perspect. Biol. 2015;7(10):a020545. doi: 10.1101/cshperspect.a020545
27. Liu G., Li M., Qian S., Yu L., Qian L., Feng X. Interleukin-35 exhibits protective effects in a rat model of hypoxic-ischemic encephalopathy through the inhibition of microglia-mediated inflammation. Transl. Pediatr. 2022;11(5):651–662. doi: 10.21037/tp-22-100
28. Tan Z., Yang G., Qiu J., Yan W., Liu Y., Ma Z., Li J., Liu J., Shan N. Quercetin alleviates demyelination through regulating microglial phenotype transformation to mitigate neuropsychiatric symptoms in mice with vascular dementia. Mol. Neurobiol. 2022;59(5):3140– 3158. doi: 10.1007/s12035-021-02712-3
29. Gilles F.H., Leviton A. Neonatal white matter damage and the fetal inflammatory response. Semin. Fetal. Neonatal. Med. 2020;25(4):101111. doi: 10.1016/j.siny.2020.101111
30. Jearjaroen P., Thangwong P., Tocharus C., Chaichompoo W., Suksamrarn A., Tocharus J. Hexahydrocurcumin attenuated demyelination and improved cognitive impairment in chronic cerebral hypoperfusion rats. Inflammopharmacology. 2024;32(2):1531–1544. doi: 10.1007/s10787-023-01406-7
31. Clark I.A., Vissel B. Autocrine positive feedback of tumor necrosis factor from activated microglia proposed to be of widespread relevance in chronic neurological disease. Pharmacol. Res. Perspect. 2023;11(5):e01136. doi: 10.1002/prp2.1136
32. Sedel F., Béchade C., Vyas S., Triller A. Macrophage-derived tumor necrosis factor alpha, an early developmental signal for motoneuron death. J. Neurosci. 2004;24(9):2236–2246. doi: 10.1523/JNEUROSCI.4464-03.2004
33. Franki I., Desloovere K., de Cat J., Feys H., Molenaers G., Calders P., Vanderstraeten G., Himpens E., van Broeck C. The evidence-base for basic physical therapy techniques targeting lower limb function in children with cerebral palsy: a systematic review using the International Classification of Functioning, Disability and Health as a conceptual framework. J. Rehabil. Med. 2012;44(5):385–395. doi: 10.2340/16501977-0983
34. Solanki R., Karande A., Ranganathan P. Emerging role of gut microbiota dysbiosis in neuroinflammation and neurodegeneration. Front. Neurol. 2023;14:1149618. doi: 10.3389/fneur.2023.1149618
35. Vieira C.P., Lelis C.A., Ochioni A.C., Rosário D.K.A., Rosario I.L.S., Vieira I.R.S., Carvalho A.P.A., Janeiro J.M., da Costa M.P., Lima F.R.S., … Junior C.A.C. Estimating the therapeutic potential of NSAIDs and linoleic acid-isomers supplementation against neuroinflammation. Biomed. Pharmacother. 2024;177:116884. doi: 10.1016/j.biopha.2024.116884
36. Kumari S., Dhapola R., Sharma P., Singh S.K., Reddy D.H. Implicative role of cytokines in neuroinflammation-mediated AD and associated signaling pathways: current progress in molecular signaling and therapeutics. Ageing Res. Rev. 2023;102098. doi: 10.1016/j.arr.2023.102098
37. Ramesh G., MacLean A.G., Philipp M.T. Cytokines and chemokines at the crossroads of neuroinflammation, neurodegeneration, and neuropathic pain. Mediators Inflamm. 2013;2013:480739. doi: 10.1155/2013/480739
38. Guha A., Husain M.A., Si Y., Nabors L.B., Filippova N., Promer G., Smith R., King P.H. RNA regulation of inflammatory responses in glia and its potential as a therapeutic target in central nervous system disorders. Glia. 2023;71(3):485–508. doi: 10.1002/glia.24288
39. Sharma S., Bhonde R. Mesenchymal stromal cells are genetically stable under a hostile in vivo-like scenario as revealed by in vitro micronucleus test. Cytotherapy. 2015;17(10):1384–1395. doi: 10.1016/j.jcyt.2015.07.004
40. Mińko A., Turoń-Skrzypińska A., Rył A., Mańkowska K., Cymbaluk-Płoska A., Rotter I. The importance of the concentration of selected cytokines (IL-6, IL-10, IL-12, IL-15, TNF-α) and inflammatory markers (CRP, NLR, PLR, LMR, SII) in predicting the course of rehabilitation for patients after COVID-19 infection. Biomedicines. 2024;12(9):2055. doi: 10.3390/biomedicines12092055
41. Magalhães R.C., Filha R.D.S., Vieira É.L.M., Teixeira A.L., Moreira J.M., Simões E Silva A.C. Rehabilitation intervention is associated with improved neurodevelopment and modulation of inflammatory molecules in children with cerebral palsy. J. Child Neurol. 2024;39(9-10):324–333. doi: 10.1177/08830738241273436
42. Nash D., Hughes M.G., Butcher L., Aicheler R., Smith P., Cullen T., Webb R. IL-6 signaling in acute exercise and chronic training: Potential consequences for health and athletic performance. Scand. J. Med. Sci. Sports. 2023;33(1):4–19. doi: 10.1111/sms.14241
43. Vella C.A., Allison M.A., Cushman M., Jenny N.S., Miles M.P., Larsen B., Lakoski S.G., Michos E.D., Blaha M.J. Physical activity and adiposity-related inflammation: the MESA. Med. Sci. Sports. Exerc. 2017;49(5):915–921. doi: 10.1249/MSS.0000000000001179
44. Hamer M., Sabia S., Batty G.D., Shipley M.J., Tabák A.G., Singh-Manoux A., Kivimaki M. Physical activity and inflammatory markers over 10 years: follow-up in men and women from the Whitehall II cohort study. Circulation. 2012;126(8):928–933. doi: 10.1161/CIRCULATIONAHA.112.103879
45. Libardi C.A., de Souza G.V., Cavaglieri C.R., Madruga V.A., Chacon-Mikahil M.P. Effect of resistance, endurance, and concurrent training on TNF-α, IL-6, and CRP. Med. Sci. Sports. Exerc. 2012;44(1):50– 56. doi: 10.1249/MSS.0b013e318229d2e9
46. Park S.S., Park S.H., Jeong H.T., Shin M.S., Kim M.K., Kim B.K., Yoon H.S., Kim S.H., Kim T.W. The effect of treadmill exercise on memory function and gut microbiota composition in old rats. J. Exerc. Rehabil. 2024;20(6):205–212. doi:10.12965/jer.2448692.346
47. Feng H., Qi Y., Wang X., Chen F., Li X. Treadmill exercise decreases inflammation via modulating IL-6 expression in the rat model of middle cerebral artery occlusion. Neurocrit. Care. 2023;38(2):279–287. doi: 10.1007/s12028-022-01575-3
48. Zheng G., Qiu P., Xia R., Lin H., Ye B., Tao J., Chen L. Effect of aerobic exercise on inflammatory markers in healthy middle-aged and older adults: a systematic review and meta-analysis of randomized controlled trials. Front. Aging Neurosci. 2019;11:98. doi: 10.3389/fnagi.2019.00098
49. da Cunha M.J., Pires Dorneles G., Peres A., Maurer S., Horn K., Souza Pagnussat A. tDCS does not add effect to foot drop stimulator and gait training in improving clinical parameters and neuroplasticity biomarkers in chronic post-stroke: randomized controlled trial. Int. J. Neurosci. 2024;134(12):1518–1527. doi: 10.1080/00207454.2023.2272041
50. Reid L.B., Rose S.E., Boyd R.N. Rehabilitation and neuroplasticity in children with unilateral cerebral palsy. Nat. Rev. Neurol. 2015;11(7):390–400. doi: 10.1038/nrneurol.2015.97
51. Reid S., Hamer P., Alderson J., Lloyd D. Neuromuscular adaptations to eccentric strength training in children and adolescents with cerebral palsy. Dev. Med. Child Neurol. 2010;52(4):358–363. doi: 10.1111/j.1469-8749.2009.03409.x
52. Hou S., Wu G., Liang J., Cheng H., Chen C. Hyperbaric oxygen on rehabilitation of brain tumors after surgery and effects on TNF-α and IL-6 levels. Oncol. Lett. 2019;17(3):3277–3282. doi: 10.3892/ol.2019.10000
53. Sharova O., Smiyan O., Borén T. Immunological effects of cerebral palsy and rehabilitation exercises in children. Brain Behav. Immun. Health. 2021;18:100365. doi: 10.1016/j.bbih.2021.100365
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