Головной мозг плода и преэклампсия: нарушение нейро­развития и его потенциальные маркеры

1. Сидорова И.С., Манагадзе И.Д. Современная концепция развития преэклампсии: новые данные. Акушерство и гинекология. 2025; 2: 5-13.
2. Kadic A.S., Kurjak A. Cognitive functions of the fetus. Ultraschall. Med. 2018; 39(2): 181-9. English. https://dx.doi.org/10.1055/s-0043-123469
3. Fagard J., Esseily R., Jacquey L., O'Regan K., Somogyi E. Fetal origin of sensorimotor behavior. Front. Neurorobot. 2018; 12: 23. https://dx.doi.org/10.3389/fnbot.2018.00023
4. Mariani B., Nicoletti G., Barzon G., Ortiz Barajas M.C., Shukla M., Guevara R. et al. Prenatal experience with language shapes the brain. Sci. Adv. 2023; 9(47): eadj3524. https://dx.doi.org/10.1126/sciadv.adj3524
5. Moser J., Schleger F., Weiss M., Sippel K., Semeia L., Preissl H. Magnetoencephalographic signatures of conscious processing before birth. Dev. Cogn. Neurosci. 2021; 49: 100964. https://dx.doi.org/10.1016/j.dcn.2021.100964
6. Falsaperla R., Collotta A.D., Spatuzza M., Familiari M., Vitaliti G., Ruggieri M. Evidences of emerging pain consciousness during prenatal development: a narrative review. Neurol. Sci. 2022; 43(6): 3523-32. https://dx.doi.org/10.1007/s10072-022-05968-2
7. Цехмистренко Т.А., Васильева В.А., Обухов Д.К., Шумейко Н.С. Строение и развитие коры большого мозга. М.: Издательство «Спутник+»; 2019. 538 с.
8. Циркин В.И., Трухина С.И., Трухин А.Н. Нейрофизиология: основы нейрофизиологии: учебник для вузов. 2-е изд., испр. и доп. М.: Издательство Юрайт; 2023. 504 с.
9. Ismail F.Y., Fatemi A., Johnston M.V. Cerebral plasticity: Windows of opportunity in the developing brain. Eur. J. Paediatr. Neurol. 2017; 21(1): 23-48. https://dx.doi.org/10.1016/j.ejpn.2016.07.007
10. Lopatina O.L., Panina Y.A., Malinovskaya N.A., Salmina A.B. Early life stress and brain plasticity: from molecular alterations to aberrant memory and behavior. Rev. Neurosci. 2020; 32(2): 131-42. https://dx.doi.org/10.1515/revneuro-2020-0077
11. Gumusoglu S.B., Chilukuri A.S.S., Santillan D.A., Santillan M.K., Stevens H.E. Neurodevelopmental outcomes of prenatal preeclampsia exposure. Trends Neurosci. 2020; 43(4): 253-68. https://dx.doi.org/10.1016/j.tins.2020.02.003
12. Kay V.R., Rätsep M.T., Cahill L.S., Hickman A.F., Zavan B., Newport M.E. et al. Effects of placental growth factor deficiency on behavior, neuroanatomy, and cerebrovasculature of mice. Physiol. Genom. 2018; 50(10): 862-75. https://dx.doi.org/10.1152/physiolgenomics.00076.2018
13. Liu X., Zhao W., Liu H., Kang Y., Ye C., Gu W. et al. Developmental and functional brain impairment in offspring from preeclampsia-like rats. Mol. Neurobiol. 2016; 53(2): 1009-19. https://dx.doi.org/10.1007/s12035-014-9060-7
14. González-Rojas A., Valencia-Narbona M. Neurodevelopmental disruptions in children of preeclamptic mothers: pathophysiological mechanisms and consequences. Int. J. Mol. Sci. 2024; 25(7): 3632. https://dx.doi.org/10.3390/ijms25073632
15. Maher G.M., Dalman C., O’Keeffe G.W., Kearney P.M., McCarthy F.P., Kenny L.C. et al. Association between preeclampsia and attention-deficit hyperactivity disorder: a population-based and sibling-matched cohort study. Acta Psychiatr. Scand. 2020; 142(4): 275-83. https://dx.doi.org/10.1111/acps.13162
16. Kong L., Chen X., Liang Y., Forsell Y., Gissler M., Lavebratt C. Association of preeclampsia and perinatal complications with offspring neurodevelopmental and psychiatric disorders. JAMA Netw. Open. 2022; 5(1): e2145719. https://dx.doi.org/10.1001/jamanetworkopen.2021.45719
17. Zhao J., Xia L. Association between hypertensive disorders of pregnancy and risk of attention-deficit/hyperactivity disorder in the offspring: a systematic review and meta-analysis. Hypertens. Pregnancy. 2022; 41(3-4): 149-58. https://dx.doi.org/10.1080/10641955.20
18. Maher G.M., O’Keeffe G.W., Dalman C., Kearney P.M., McCarthy F.P., Kenny L.C., Khashan A.S. Association between preeclampsia and autism spectrum disorder: a population-based study. J. Child Psychol. Psychiatry. 2020; 61(2):131-9. doi: 10.1111/jcpp.13127
19. Zhu Y., Wei S.Y., Fu X.T., Cheng X., Lin X.H. Potential mechanism connecting preeclampsia to autism spectrum disorder in offspring: the role of microglial abnormalities. Front. Biosci. (Landmark). 2025, 30(8): 36412. https://dx.doi.org/10.31083/FBL36412
20. Кан Н.Е., Леонова А.А., Гусар В.А., Чаговец В.В., Тютюнник В.Л., Волочаева М.В., Солдатова Е.Е., Рыжова К.О., Серебрякова А.П. Критерии оценки дисфункции нейрогенеза плода с ранней задержкой роста с использованием внеклеточных везикул. Акушерство и гинекология. 2025; 3: 56-64.
21. Волочаева М.В., Кан Н.Е., Тютюнник В.Л., Леонова А.А., Солдатова Е.Е., Рыжова К.О. Особенности постнатального развития детей с задержкой роста (катамнестическое исследование). Акушерство и гинекология. 2025; 3: 65-71.
22. Scott H., Phillips T.J., Stuart G.C., Rogers M.F., Steinkraus B.R., Grant S. et al. Preeclamptic placentae release factors that damage neurons: implications for foetal programming of disease. Neuronal Signal. 2018; 2(4): NS20180139. https://dx.doi.org/10.1042/NS20180139
23. Sattwika P.D., Schuermans A., Cutler H.R., Alkhodari M., Anggraeni V.Y., Nurdiati D.S. et al. Multi-organ phenotypes of offspring born following hypertensive disorders of pregnancy: a systematic review. J. Am. Heart Assoc. 2024; 13(21): e033617. https://dx.doi.org/10.1161/JAHA.123.033617
24. Gumusoglu S.B., Chilukuri A.S.S., Hing B.W.Q., Scroggins S.M., Kundu S., Sandgren J.A. et al. Altered offspring neurodevelopment in an arginine vasopressin preeclampsia model. Transl. Psychiatry. 2021; 11(1): 79. https://dx.doi.org/10.1038/s41398-021-01205-0
25. Wang H., László K.D., Gissler M., Li F., Zhang J., Yu Y. et al. Maternal hypertensive disorders and neurodevelopmental disorders in offspring: a population-based cohort in two nordic countries. Eur. J. Epidemiol. 2021; 36: 519-30. https://dx.doi.org/10.1007/s10654-021-00756-2
26. Gumusoglu S.B. The role of the placenta-brain axis in psychoneuroimmune programming. Brain Behav. Immun. Health. 2024; 36: 100735. https://doi.org/10.1016/j.bbih.2024.100735
27. Bucher V., Herrock O.T., Schell S., Visser J., Imberg H., Burke J. et al. Blood-brain barrier injury and neuroinflammation in pre-eclampsia and eclampsia. EBioMedicine. 2025; 116:105742. https://doi.org/10.1016/j.ebiom.2025.105742
28. Maeda K.J., McClung D.M., Showmaker K.C., Warrington J.P., Ryan M.J., Garrett M.R. et al. Endothelial cell disruption drives increased blood-brain barrier permeability and cerebral edema in the Dahl SS/jr rat model of superimposed preeclampsia. Am. J. Physiol. Heart Circ. Physiol. 2021; 320(2): H535-H548. https://dx.doi.org/10.1152/ajpheart.00383.2020
29. Bergman L., Torres-Vergara P., Penny J., Wikström J., Nelander M., Leon J. et al. Investigating maternal brain alterations in preeclampsia: the need for a multidisciplinary effort. Curr. Hypertens Rep. 2019; 21(9): 72. https://dx.doi.org/10.1007/s11906-019-0977-0
30. Bergman L., Hastie R., Zetterberg H., Blennow K., Schell S., Langenegger E. et al. Evidence of neuroinflammation and blood-brain barrier disruption in women with preeclampsia and eclampsia. Cells. 2021; 10(11): 3045. https://dx.doi.org/10.3390/cells10113045
31. Mahendra V., Clark S.L., Suresh M.S. Neuropathophysiology of preeclampsia and eclampsia: A review of cerebral hemodynamic principles in hypertensive disorders of pregnancy. Pregnancy Hypertens. 2021; 23: 104-11. https://dx.doi.org/10.1016/j.preghy.2020.10.013
32. Escudero C., Kupka E., Ibañez B., Sandoval H., Troncoso F., Wikström A.K. et al. Brain vascular dysfunction in mothers and their children exposed to preeclampsia. Hypertension. 2023; 80(2): 242-56. https://dx.doi.org/10.1161/HYPERTENSIONAHA.122.19408
33. Friis T., Wikström A.K., Acurio J., León J., Zetterberg H., Blennow K. et al. Cerebral biomarkers and blood-brain barrier integrity in preeclampsia. Cells. 2022; 11(5): 789. https://dx.doi.org/10.3390/cells11050789
34. Bergman L., Hastie R., Bokström-Rees E., Zetterberg H., Blennow K., Schell S. et al. Cerebral biomarkers in neurologic complications of preeclampsia. Am. J. Obstet. Gynecol. 2022; 227(2): 298.e1-298.e10. https://dx.doi.org/10.1016/j.ajog.2022.02.036
35. Liao J., Zhang Z., Huang W., Huang Q., Bi G. Neonatal neuron specific enolase, a sensitive biochemical marker of neuronal damage, is increased in preeclampsia: A retrospective cohort study. Brain Dev. 2020; 42(8): 564-71. https://dx.doi.org/10.1016/j.braindev.2020.04.011
36. Karampas G., Tzelepis A., Koulouraki S., Lykou D., Metallinou D., Erlandsson L. et al. The utility of maternal blood S100B in women with suspected or established preeclampsia-a systematic review. Biomolecules. 2025;15(6): 840. https://dx.doi.org/10.3390/biom15060840
37. Wu J., Sheng X., Zhou S., Fang C., Song Y., Wang H. et al. Clinical significance of S100B protein in pregnant woman with early-onset severe preeclampsia. Ginekol. Pol. 2024; 95(9): 711-7. https://dx.doi.org/10.5603/GP.a2021.0126
38. Wang Y., Guo B., Zhao K., Yang L., Chen T. Correlation between cognitive impairment and serum phosphorylated tau181 protein in patients with preeclampsia. Front. Aging Neurosci. 2023; 15: 1148518. https://dx.doi.org/10.3389/fnagi.2023.1148518
39. Jash S., Banerjee S., Cheng S., Wang B., Qiu C., Kondo A. et al. Cis P-tau is a central circulating and placental etiologic driver and therapeutic target of preeclampsia. Nat. Commun. 2023; 14(1): 5414. https://dx.doi.org/10.1038/s41467-023-41144-6
40. Andersson M., Oras J., Thörn S.E., Karlsson O., Kälebo P., Zetterberg H. et al. Signs of neuroaxonal injury in preeclampsia-A case control study. PLoS One. 2021; 16(2): e0246786. https://dx.doi.org/10.1371/journal.pone.0246786
41. Gu X., Rana S., Ngo L., Mueller A., Dillon S., Salahuddin S. et al. Plasma markers of neurological injury are elevated in preeclampsia. Pregnancy Hypertens. 2025; 42: 101265. https://dx.doi.org/10.1016/j.preghy.2025.101265
42. Vinci L., Ravarino A., Fanos V., Naccarato A.G., Senes G., Gerosa C. et al. Immunohistochemical markers of neural progenitor cells in the early embryonic human cerebral cortex. Eur. J. Histochem. 2016; 60(1): 2563. https://dx.doi.org/10.4081/ejh.2016.2563
43. Сидорова И.С., Манагадзе И.Д. Современные представления о преэклампсии с учетом роли нейронспецифических белков головного мозга плода. Акушерство и гинекология. 2025; 1: 5-11.
44. Jurewicz E., Filipek A. Ca2+-binding proteins of the S100 family in preeclampsia. Placenta. 2022; 127: 43-51. https://dx.doi.org/10.1016/j.placenta.2022.07.018
45. Evers K.S., Atkinson A., Barro C., Fisch U., Pfister M., Huhn E.A. et al. Neurofilament as neuronal injury blood marker in preeclampsia. Hypertension. 2018; 71(6): 1178-84. https://dx.doi.org/10.1161/HYPERTENSIONAHA.117.10314
46. Medegan Fagla B., Buhimschi I.A. Protein misfolding in pregnancy: current insights, potential mechanisms, and implications for the pathogenesis of preeclampsia. Molecules. 2024; 29(3): 610. https://dx.doi.org/10.3390/molecules29030610
47. Bergman L., Zetterberg H., Kaihola H., Hagberg H., Blennow K., Åkerud H. Blood-based cerebral biomarkers in preeclampsia: Plasma concentrations of NfL, tau, S100B and NSE during pregnancy in women who later develop preeclampsia - A nested case control study. PLoS One. 2018; 13(5): e0196025. https://dx.doi.org/10.1371/journal.pone.0196025
48. Ayaydın H., Kirmit A., Çelik H., Akaltun İ., Koyuncu İ., Bilgen Ulgar Ş. High serum levels of serum 100 beta protein, neuron-specific enolase, tau, active caspase-3, M30 and M65 in children with autism spectrum disorders. Clin. Psychopharmacol. Neurosci. 2020;18(2): 270-8. https://dx.doi.org/10.9758/cpn.2020.18.2.270
49. Bagnall-Moreau C., Spielman B., Brimberg L. Maternal brain reactive antibodies profile in autism spectrum disorder: an update. Transl. Psychiatry. 2023; 13(1): 37. https://dx.doi.org/10.1038/s41398-023-02335-3
50. Krakowiak P., Walker C.K., Tancredi D., Hertz-Picciotto I., Van de Water J. Autism-specific maternal anti-fetal brain autoantibodies are associated with metabolic conditions. Autism Res. 2017; 10(1): 89-98. https://dx.doi.org/10.1002/aur.1657

Поступила 07.11.2025

Принята в печать 24.03.2026