Sex differences in neuroplasticity and functional recovery after neurosurgical interventions
Журнал: Вопросы нейрохирургии имени Н.Н. Бурденко. 2026;90(5):113-119.
DOI: 10.17116/neiro202690051113
Read: 862 раза
Abstract
OBJECTIVE
To analyze modern data on the influence of biological sex and gender factors on mechanisms of neuroplasticity and functional recovery after neurosurgical interventions.
MATERIAL AND METHODS
We reviewed the databases (PubMed, Scopus, Russian Science Citation Index (RSCI) and Google Scholar) over the past 10 years. The review covers clinical trials, prospective and retrospective cohort studies and animal models of traumatic brain injury, surgery for brain cancer, vascular accidents and spinal cord injury. The main parameters were diffusion tensor imaging data, functional MRI, hormonal profile and standardized clinical scales including the modified Rankin scale, Barthel index, ASIA and FIM scales.
RESULTS
Female brain has better interhemispheric connectivity that provides adaptive advantage in focal lesions of dominant hemisphere. Male brain is optimized for intrahemispheric signaling promoting faster motor coordination. Estrogens and progesterone have neuroprotective effect through modulation of inflammatory response and support of myelination, but this effect depends on age and phase of reproductive cycle. In clinical practice, women often demonstrate lower rates of functional independence at discharge after stroke due to comorbidity and social factors, despite equal or superior potential for neurological recovery compared to men.
CONCLUSION
Biological sex is a critical determinant of neurosurgical outcomes. Discrepancy between biological recovery potential (higher in women) and actual functional outcomes (often better in men) highlights the need to develop personalized, gender-specific rehabilitation protocols taking into account specifics of connectome and hormonal backgrounds.
Keywords
- neuroplasticity
- neurosurgery
- gender differences
- sexual dimorphism
- functional recovery
- estrogens
- neuroimaging
- connectome
- rehabilitation
- neuroprotection
Дата поступления: 05.01.2026
Дата принятия в печать: 20.07.2026
Дата публикации: 16.10.2026
- Kakhkharov RA, Kadyrov ShU, Ogurtsova AA, Bayev AA, Afandiev RM, Pronin IN. Surgical treatment of brain tumors adjacent to corticospinal tract in children. Burdenko’s Journal of Neurosurgery. 2024;88(1):97-102. (In Russ.). https://doi.org/10.17116/neiro20248801197
- Gardanova ZhR, Esaulov VI, Sedova EO, Ilgov VI, Veprentsova SYu, Kalina SA, Fetisova LN, Matreshin IM. Gender-specific risk factors for suicidal behavior in adolescents. Pediatric and Adolescent Reproductive Health. 2020;16(89):131-150. (In Russ.). https://doi.org/10.33029/1816-2134-2020-16-4-131-150
- Tyuvina NA, Stolyarova AE, Morozova VD, Verbitskaya MS. Gender differences in the clinical course of depression in bipolar disorder. Neurology, Neuropsychiatry, Psychosomatics. 2021;13(2):47-55. (In Russ.). https://doi.org/10.14412/2074-2711-2021-2-47-55
- Gupte R, Brooks W, Vukas R, Pierce J, Harris J. Sex Differences in Traumatic Brain Injury: What We Know and What We Should Know. Journal of Neurotrauma. 2019;36(22):3063-3091. https://doi.org/10.1089/neu.2018.6171
- Beery AK, Zucker I. Sex bias in neuroscience and biomedical research. Neuroscience and BioBehavioral Reviews. 2011;35(3):565-572. https://doi.org/10.1016/j.neubiorev.2010.07.002
- Kim H, Lee H. Current status and significance of research on sex differences in neuroscience: a narrative review and bibliometric analysis. Ewha Medical Journal. 2024;47(2):e16. https://doi.org/10.12771/emj.2024.e16
- Mamlouk GM, Dorris DM, Barrett LR, Meitzen J. Sex bias and omission in neuroscience research is influenced by research model and journal, but not reported NIH funding. Frontiers in Neuroendocrinology. 2020;57:100835. https://doi.org/10.1016/j.yfrne.2020.100835
- Mollayeva T, Mollayeva S, Pacheco N, Colantonio A. Systematic Review of Sex and Gender Effects in Traumatic Brain Injury: Equity in Clinical and Functional Outcomes. Frontiers in Neurology. 2021;12:678971. https://doi.org/10.3389/fneur.2021.678971
- Yusupov FA, Ydyrysov IT, Abdykadyrov MSh, Yusupova TF. Age and gender aspects of parkinson’s disease. Clinical Medicine (Russian Journal). 2025; 103(1):13-22. (In Russ.). https://doi.org/10.30629/0023-2149-2025-103-1-13-22
- Yao S, Liebenthal E, Juvekar P, Bunevicius A, Vera M, Rigolo L, Golby AJ, Tie Y. Sex Effect on Presurgical Language Mapping in Patients With a Brain Tumor. Frontiers in Neuroscience. 2020;14:4. https://doi.org/10.3389/fnins.2020.00004
- Zárate S, Stevnsner T, Gredilla R. Role of Estrogen and Other Sex Hormones in Brain Aging. Neuroprotection and DNA Repair. Frontiers in Aging Neuroscience. 2017;9:430. https://doi.org/10.3389/fnagi.2017.00430
- Barth C, Villringer A, Sacher J. Sex hormones affect neurotransmitters and shape the adult female brain during hormonal transition periods. Frontiers in Neuroscience. 2015;9:37. https://doi.org/10.3389/fnins.2015.00037
- Ghosson A, Soufan F, Kaddoura H, Fares E, Uwishema O. Understanding the Intersection Between Hormonal Dynamics and Brain Plasticity in Alzheimer’s Disease: A Narrative Review for Implementing New Therapeutic Strategies. Health Science Reports. 2025;8(7):e70975. https://doi.org/10.1002/hsr2.70975
- Brotfain E, Gruenbaum SE, Boyko M, Kutz R, Zlotnik A, Klein M. Neuroprotection by Estrogen and Progesterone in Traumatic Brain Injury and Spinal Cord Injury. Current Neuropharmacology. 2016;14(6):641-653. https://doi.org/10.2174/1570159x14666160309123554
- Wagner AK, McCullough EH, Niyonkuru C, Ozawa H, Loucks TL, Dobos JA, Brett CA, Santarsieri M, Dixon CE, Berga SL, Fabio A. Acute serum hormone levels: characterization and prognosis after severe traumatic brain injury. Journal of Neurotrauma. 2011;28(6):871-888. https://doi.org/10.1089/neu.2010.1586
- Pearson-Fuhrhop KM, Kleim JA, Cramer SC. Brain plasticity and genetic factors. Topics in Stroke Rehabilitation. 2009;16(4):282-299. https://doi.org/10.1310/tsr1604-282
- Ingalhalikar M, Smith A, Parker D, Satterthwaite TD, Elliott MA, Ruparel K, Hakonarson H, Gur RE, Gur RC, Verma R. Sex differences in the structural connectome of the human brain. Proceedings of the National Academy of Sciences of the United States of America. 2014;111(2):823-828. https://doi.org/10.1073/pnas.1316909110
- Kirby ED, Andrushko JW, Rinat S, D’Arcy RCN, Boyd LA. Investigating female versus male differences in white matter neuroplasticity associated with complex visuo-motor learning. Scientific Reports. 2024;14(1):5951. https://doi.org/10.1038/s41598-024-56453-z
- Kirby ED, Andrushko JW, Boyd LA, Koschutnig K, D’Arcy RCN. Sex differences in patterns of white matter neuroplasticity after balance training in young adults. Frontiers in Human Neuroscience. 2024;18:1432830. https://doi.org/10.3389/fnhum.2024.1432830
- Lenga P, Scherer M, Dao Trong P, Krieg SM, Suchorska B. Sex-specific disparities in postoperative adverse events following intracranial tumor surgery: insights from a tertiary neurosurgical center. Acta Neurochirurgica. 2025;167(1):292. https://doi.org/10.1007/s00701-025-06708-z
- Shaywitz BA, Shaywitz SE, Pugh KR, Constable RT, Skudlarski P, Fulbright RK, Bronen RA, Fletcher JM, Shankweiler DP, Katz L, Gore JC. Sex differences in the functional organization of the brain for language. Nature. 1995;373(6515):607-609. https://doi.org/10.1038/373607a0
- Pasquini L, Peck KK, Tao A, Del Ferraro G, Correa DD, Jenabi M, Kobylarz E, Zhang Z, Brennan C, Tabar V, Makse H, Holodny AI. Longitudinal Evaluation of Brain Plasticity in Low-Grade Gliomas: fMRI and Graph-Theory Provide Insights on Language Reorganization. Cancers. 2023; 15(3):836. https://doi.org/10.3390/cancers15030836
- Saviola F, Zigiotto L, Novello L, Zacà D, Annicchiarico L, Corsini F, Rozzanigo U, Papagno C, Jovicich J, Sarubbo S. The role of the default mode network in longitudinal functional brain reorganization of brain gliomas. Brain Structure & Function. 2022;227(9):2923-2937. https://doi.org/10.1007/s00429-022-02490-1
- Surbeck W, Herbet G, Duffau H. Sexuality after surgery for diffuse low-grade glioma. Neuro-Oncology. 2015;17(4):574-579. https://doi.org/10.1093/neuonc/nou326
- Späni CB, Braun DJ, Van Eldik LJ. Sex-related responses after traumatic brain injury: Considerations for preclinical modeling. Frontiers in Neuroendocrinology. 2018;50:52-66. https://doi.org/10.1016/j.yfrne.2018.03.006
- Colantonio A, Harris JE, Ratcliff G, Chase S, Ellis K. Gender differences in self reported long term outcomes following moderate to severe traumatic brain injury. BMC Neurology. 2010;10:102. https://doi.org/10.1186/1471-2377-10-102
- Wang S, Hu L, Cao J, Huang W, Sun C, Zheng D, Wang Z, Gan S, Niu X, Gu C, Bai G, Ye L, Zhang D, Zhang N, Yin B, Zhang M, Bai L. Sex Differences in Abnormal Intrinsic Functional Connectivity After Acute Mild Traumatic Brain Injury. Frontiers in Neural Circuits. 2018;12:107. https://doi.org/10.3389/fncir.2018.00107
- Amgalan A, Maher AS, Imms P, Ha MY, Fanelle TA, Irimia A. Functional Connectome Dynamics After Mild Traumatic Brain Injury According to Age and Sex. Frontiers in Aging Neuroscience. 2022;14:852990. https://doi.org/10.3389/fnagi.2022.852990
- Wright DW, Yeatts SD, Silbergleit R, Palesch YY, Hertzberg VS, Frankel M, Goldstein FC, Caveney AF, Howlett-Smith H, Bengelink EM, Manley GT, Merck LH, Janis LS, Barsan WG; NETT Investigators. Very early administration of progesterone for acute traumatic brain injury. The New England Journal of Medicine. 2014;371(26):2457-2466. https://doi.org/10.1056/NEJMoa1404304
- Marx CE, Naylor JC, Kilts JD, Dunn CE, Tupler LA, Szabo ST, Capehart BP, Morey RA, Shampine LJ, Acheson SK. Neurosteroids and Traumatic Brain Injury: Translating Biomarkers to Therapeutics; Overview and Pilot Investigations in Iraq and Afghanistan Era Veterans. In: Laskowitz D, Grant G, eds. Translational Research in Traumatic Brain Injury. Boca Raton (FL): CRC Press/Taylor and Francis Group; 2016.
- Sipski ML, Jackson AB, Gómez-Marín O, Estores I, Stein A. Effects of gender on neurologic and functional recovery after spinal cord injury. Archives of Physical Medicine and Rehabilitation. 2004;85(11):1826-1836. https://doi.org/10.1016/j.apmr.2004.04.031
- Benedict B, Javeed S, Kaleem M, Zhang JK, Yakdan S, Botterbush K, Wen H, Chen Y, Belzberg A, Tuffaha S, Burks SS, Levi AD, Zager EL, Faraji AH, Mahan MA, Midha R, Wilson TJ, Juknis N, Greenberg JK, Ray WZ; Nerve Transfers in Spinal Cord Injury (NT-SCI) Consortium. Sex-Related Differences in Functional and Neurological Outcomes of Spinal Cord Injury. Neurosurgery. 2026;98(1):246-255. https://doi.org/10.1227/neu.0000000000003615
- Kim JS, Lee KB, Roh H, Ahn MY, Hwang HW. Gender differences in the functional recovery after acute stroke. Journal of Clinical Neurology. 2010;6(4):183-188. https://doi.org/10.3988/jcn.2010.6.4.183
- Kautzky-Willer A, Harreiter J, Thomas A, Burger J, Schneeweiß U, Deischinger C, Klein W, Moser H. Women With Cerebral Infarction Feature Worse Clinical Profiles at Admission but Comparable Success to Men During Long-Term Inpatient Neurorehabilitation. Frontiers in Aging Neuroscience. 2021;13:663215. https://doi.org/10.3389/fnagi.2021.663215
- Cai Y, Liu Z, Jia C, Zhao J, Chai S, Li Z, Xu C, Zhang T, Ma Y, Ma C, Chen X, Jiang P, Zhao W, Chen J, Xiong N. Comparison of Sex Differences in Outcomes of Patients With Aneurysmal Subarachnoid Hemorrhage: A Single-Center Retrospective Study. Frontiers in Neurology. 2022;13:853513. https://doi.org/10.3389/fneur.2022.853513
- Cocco C, Siotto M, Guerrini A, Germanotta M, Falchini F, Cipollini V, Cortellini L, Pavan A, Lattanzi S, Insalaco S, Papadopoulou D, Ruco E, Antonacci E, Aprile IG. Gender Differences in Subacute Post-Stroke Patients During Rehabilitation: Functional, Cognitive, and Nutritional Insights. Neurology International. 2025;17(12):193. https://doi.org/10.3390/neurolint17120193
- Faria AL, Almeida Y, Branco D, Câmara J, Cameirão M, Ferreira L, Moreira A, Paulino T, Rodrigues P, Spinola M, Vilar M, Bermúdez i Badia S, Simões M, Fermé E. NeuroAIreh@b: an artificial intelligence-based methodology for personalized and adaptive neurorehabilitation. Frontiers in Neurology. 2024;14:1258323. https://doi.org/10.3389/fneur.2023.1258323
Recommended articles:
Clinical significance of silent strokes in carotid artery surgery: a systematic review and meta-analysis.Russian Journal of Anesthesiology and Reanimatology. 2026;(5):72-80
The effect of enhanced external contrpulsation on the diaphragm mobility and power of the patient with a combination of bronchial asthma and chronic obstructive pulmonary disease.Russian Journal of Preventive Medicine. 2026;29(9):103-109
Clinical heterogeneity and neurobiological mechanisms of asthenia.Russian Journal of Preventive Medicine. 2026;29(9):77-85
TECAR therapy for complications after brachioplasty.Plastic Surgery and Aesthetic Medicine. 2026;(2):62-67
Therapy prospects for post-stroke aphasia.S.S. Korsakov Journal of Neurology and Psychiatry. 2026;126(4-2):86-91
The effect of Cerebrolysin on the development of skills in patients after acute cerebrovascular accidents.S.S. Korsakov Journal of Neurology and Psychiatry. 2026;126(2):32-38
Postural disorders in practice of rehabilitation specialist (Handbook, 2025).Regenerative Biotechnologies, Preventive, Digital and Predictive Medicine. 2025;2(4):91-129
SPA rehabilitation of patients with lumbar spine dorsopathy.Regenerative Biotechnologies, Preventive, Digital and Predictive Medicine. 2025;2(4):14-19
Improving the quality of life and the possibility of pathogenetic therapy in adult patients with cerebral palsy.S.S. Korsakov Journal of Neurology and Psychiatry. 2025;125(10):75-84
Burnout syndrome: prevention, treatment and rehabilitation.Regenerative Biotechnologies, Preventive, Digital and Predictive Medicine. 2025;2(3):61-68