Features of pathogenesis and early diagnostic criteria of hypoxic-ischemic brain injury in newborns (part 2)

Authors

  • V.Yu. Martyniuk State Institution “Lukianova Institute of Pediatrics, Obstetrics and Gynecology of the National Academy of Medical Sciences of Ukraine”, Kyiv, Ukraine
  • V.B. Shveikina Shupyk National Medical Academy of Postgraduate Education of the Ministry of Health of Ukraine, Kyiv, Ukraine
  • T.K. Znamenska Shupyk National Medical Academy of Postgraduate Education of the Ministry of Health of Ukraine, Kyiv, Ukraine
  • L.I. Nikulina Shupyk National Medical Academy of Postgraduate Education of the Ministry of Health of Ukraine, Kyiv, Ukraine

DOI:

https://doi.org/10.22141/2224-0713.16.8.2020.221955

Keywords:

newborn, brain, hypoxia, neuron-specific proteins, review

Abstract

The article deals with the current problem of neonatology and pediatric neurology — the issues of early diagnosis of perinatal hypoxic-ischemic brain injury in newborns, particularly, in prematurely born children. The work considers modern literature data on the mechanisms of hypoxic-ischemic perinatal brain damage. New data on the functioning, injury, as well as the mechanism of cell death of neuronal and glial origin in the developing brain are presented. It was shown that excitotoxicity (glutamatergic system), oxidative stress and aseptic inflammation are involved in the realization of this mechanism, the final result of which is cell death by necrosis and pathological apoptosis. It was emphasized that in immature neuronal tissue, the death of neurons occurs not only by the above paths, but also due to the combined necrotic-apoptotic (necroptotic) mechanism. The ambiguous role of glutamate receptors in the developing brain is analyzed. Literature data are presented that excitotoxicity, oxidative stress and inflammation against the background of peculiarities mitochondrial functioning in the brain lead to the onset of pathological apoptosis. It has been determined that the most promising in the early diagnosis of hypoxic-ischemic damage to the central nervous system in newborns, in particular premature babies, is the study of the level of neuron-specific proteins and antibodies to them, as well as proteins associated with the plasma membrane — intercellular adhesion molecules. The article analyzes the role of neuronal and glial markers, in particular glial fibrillary acidic protein, ubiquitin C-terminal hydrolase L1, myelin basic protein, as well as the role of pro-inflammatory cytokines in the mechanisms of damage to cells of the developing brain. The role of the membrane protein of cerebral capillary endotheliocytes, an intercellular adhesion molecule 1, as one of the markers of damage to the blood-brain barrier cells in various pathological processes, in particular hypoxia and ischemia, was determined.

References

Блинов Д.В. Иммуноферментный анализ нейроспецифических антигенов в оценке проницаемости гематоэнцефалического барьера при гипоксически-ишемических поражениях ЦНС в перинатальном периоде (клинико-экспериментальное исследование): Дис… канд. мед. наук. Москва, 2004. 153 с.

Голенченко В.А. Биологические мембраны: Биохимия: Учеб. для вузов. Под ред. Е.С. Северина. Москва: ГЭОТАР-МЕД, 2003. С. 245-248.

Гомазков О.А. Нейротрофическая регуляция и стволовые клетки мозга. Москва: Икар, 2006. 332 с.

Лисяный Н.И. Иммунная система головного мозга. Киев, 1999. 216 с.

Молекулы адгезии. Электронный ресурс. Режим доступа: http://laboratory.rusmedserv.com/files/41_Molekuly_Adgezii.pdf.

Николлс Дж.Г., Мартин А.Р., Валлас Б.Дж., Фукс П.А. От нейрона к мозгу. Пер. с англ. 4-е изд. Москва: Либриком, 2017. 672 с.

Рябухин И.А. Нейроспецифические белки в оценке проницаемости гематоэнцефалического барьера человека и животных: Дис... д-ра мед. наук. Москва, 2004. 297 с.

Таболин В.А., Володин Н.Н., Дегтярева М.В. Актуальные вопросы перинатальной иммунологии. Детская иммунология. 2004. № 1. С. 1-14.

Таранушенко Т.Е., Окунева О.С., Демьянова И.М. и др. Уровни белков нейрональной и глиальной природы в крови новорожденных при церебральной ишемии. Педиатрия. 2010. Т. 89. № 1. С. 25-31.

Технологии изучения и моделирования гематоэнцефалического барьера. Неврология XXI века: диагностические, лечебные и исследовательские технологии: Руководство для врачей: в 3 т. Под ред. М.А. Пирадова, С.Н. Иллариошкина, М.М. Танашян. Т. III. Москва: АТМО, 2015. С. 376.

Турина О.И. Моноклональные антитела к нейроспецифическим антигенам. Получение, иммунохимический анализ, исследование проницаемости гематоэнцефалического барьера: Дис... д-ра мед. наук. Москва, 2005. 269 с.

Чехонин В.П., Дмитриева Т.Б., Жирков Ю.А. Иммунохимический анализ нейроспецифических антигенов. Москва: Медицина, 2000. 415 с.

Armati Patricia, Mathey Emily. The Biology of Oligodendrocytes. Cambridge University Press, 2010. 304. https://DOI.org/10.1017/CBO9780511782121.

Back S.A., Luo N.L., Borenstein N.S. et al. Late oyligoeden-drocyte coincide with the developmental window of vulnerability for human perinatal white matter injury. J. Neurosci. 2001 Feb. 21(4). 1302-1312. PMID: 11160401. PMCID: PMC6762224.

Bavunoglu I., Genc H., Konukoglu D. et al. Oxidative stress parameters and inflammatory and immune mediators as markers of the severity of sepsis. J. Infect. Dev. Ctries. 2016 Oct. 10(10). 1045-1052. DOI: 10.3855/jidc.7585. PMID: 27801365.

Blennow M., Hagberg H., Rosengren L. Glial fibrillary acidic protein in the cerebrospinal fluid: a possible indicator of prognosis in full-term asphyxiated newborn infants? Pediatr. Res. 1995. 37(3). 260-264. DOI: 10.1203/00006450-199503000-00002. PMID: 7784132.

Brouns R., De Vil B., Cras P., De Surgeloose D. et al. Neurobiochemical markers of brain damage in cerebrospinal fluid of acute ischemic stroke patients. Clin. Chem. 2010 Mar. 56(3). 451-458. DOI: 10.1373/clinchem.2009.134122. PMID: 19959621.

Casper K.B., McCarthy K.D. GFAP-positive progenitor cells produce neurons and oligodendrocytes throughout the CNS. Mol. Cell. Neurosci. 2006 Apr. 31(4). 676-684. DOI: 10.1016/j.mcn.2005.12.006. PMID: 16458536.

Chalak L.F., Sanchez P.J., Adams-Huet B. et al. Biomar-kers for severity of neonatal hypoxic-ischemic encephalopathy and outcomes in newborns receiving hypothermia therapy. J. Pediatr. 2014 Mar. 164(3). 468-74. DOI: 10.1016/j.jpeds.2013.10.067. PMID: 24332821. PMCID: PMC4006934.

Clinicaltrials.gov [Internet]. Study Record Detail. Developmental Outcomes [cited 2016 Sep 9]. Available from: https://clinicaltrials.gov/ct2/show/NCT02264808?term=Cord+Blood++HIE&rank=11.

Covert R., Kohn J., Yousefzadeh D., Ben-Armi N., Mittendorf R. Thalamostriate Vasculopathy in Neonates in the MAGnet Trial: Association with Placental Funisitis and Intraventricular Hemmorrhage. Pediatr. Res. 1999. 45. 192. DOI: 10.1203/00006450-199904020-01139.

Bonestroo H.J., Heijnen C.J., Groenendaal F., van Bel F., Nijboer C.H. Development of cerebral gray and white matter injury and cerebral inflammation over time after inflammatory perinatal asphyxia. Developmental Neuroscience. 2015. 37(1). 78-94. DOI: 10.1159/000368770. PMID: 25634435.

Douglas-Escobar M., Yang C., Bennett J. et al. A pilot study of novel biomarkers in neonates with hypoxic-ischemic encephalopathy. Pediatr. Res. 2010 Dec. 68(6). 531-536. DOI: 10.1203/PDR.0b013e3181f85a03. PMID: 20736881. PMCID: PMC3851011.

Edgar J.D., Gabriel V., Gallimore J.R., McMillan S.A., Grant J. et al. A prospective study of the sensitivity, specifity and diagnostic performance of soluble intercellular adhesion molecule 1, highly sensitive C-reactive protein, soluble E-selectin and serum amyloid Ain the diagnosis of neonatal infection. BCM Pediatr. 2010 Apr. 10. 22. DOI: 10.1186/1471-2431-10-22. PMID: 20398379. PMCID: PMC2868836.

Ennen C.S., Huisman T.A., Savage W.J. et al. Glial fibrillary acidic protein as a biomarker for neonatal hypoxicischemic encephalopathy treated with whole-body cooling. Am. J. Obstet. Gynecol. 2011 Sep. 205(3). 251-257. DOI: 10.1016/j.ajog.2011.06.025. PMID: 21784396. MCID: PMC4011017.

Florio Р., Abella R., Marinoni E. et al. Biochemical marcers of perinatal brain damage. Front. Biosci (Schol Ed). 2010 Jan 1(2). 47-72. I:10.2741/s45. PMID: 20036928.

Gough P.J., Raines E.W. Emerging roles of ectodomain shedding in the regulation of inflammatory responses. J. Leukoc. Biol. 2006. Mar. 79(6). 1105-1116. DOI: 10.1189/jlb.0106038. PMID: 16565325.

Glickman M.H., Ciechanover A. The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Phy­siol. Rev. Journal. 2002 Apr. 82(2). 373-428. DOI: 10.1152/physrev.00027.2001. PMID: 11917093.

Goldstein G., Scheid M., Hammerling U., Schlesinger D.H., Niall H.D., Boyse E.A. Isolation of a polypeptide that has lymphocyte-differentiating properties and is probably represented universally in living cells. Proceedings of the National Academy of Sciences of the United States of America: journal. 1975 Jan. 72(1). 11-15. DOI: 10.1073/pnas.72.1.11. PMID: 1078892.

Hao Liu, Nadya Povysheva, Marie E. Rose et al. Role of UCHL1 in axonal injury and functional recovery after cerebral ischemia.PNAS. 2019 March. 116(10). 4643-4650. DOI: 10.1073/pnas.1821282116.

Chen C.Y., Sun W.Z., Kang K.H. еt al. Hypoxic preconditioning suppresses glial activation and neuroinflammation in neonatal brain insults. Mediators of Inflammation. 2015. 2015. 632592. DOI: 10.1155/2015/632592. PMID: 26273140. PMCID: PMC4530271.

Huang Z., Song L., Wang C., Chen С., Liu J.-Q. Hypoxia-ischemia upregulates TRAIL and TRAIL receptors in the immature rat brain. Dev. Neurosci. 2011. 33(6). 519-30. DOI: 10.1159/000334475.

Iida K., Takashima S. et al. Immunohistochemical study of myelination and oligodendrocytye in infants with periventricular leucomalacia. Pediatr. Neurol. Nov 1995. 13(4). 296-304. DOI: 10.1016/0887-8994(95)00192-1. PMID: 8771165.

Inder Т.Е., Anderson N.J., Spencer C., Wells S., Volpe J.J. White matter injury in the premature infant: a comparison between serial cranial sonographic and MR Qidings at term. AJNR Am. J. Neuroradiol. 2003. 24(5). 805-809. PMID: 12748075.

Kimura Y., Tanaka K. Regulatory mechanisms involved in the control of ubiquitin homeostasis. J. Biochem. Journal. 2010 Jun. 147(6). 793-798. DOI: 10.1093/jb/mvq044. PMID: 20418328.

Kjaergaard A.G., Dige A., Krog J., Tønnesen E., Wogensen L. Soluble adhesion molecules correlate with surface expression in an in vitro model of endothelial activation. Basic Clin. Pharmacol. Toxicol. 2013 Oct. 113(4). 273-279. DOI: 10.1111/bcpt.12091. PMID: 23724832.

Laerhoven H., de Haan T.R, Offringa M., Post B. et al. Prognostic tests in term neonates with hypoxic-ischemic encephalopathy: a systematic review. Pediatrics. 2013 Jan. 132(1). 89-98. DOI: 10.1542/peds.2012-1297. PMID: 23248219.

Lv H., Wang Q., Wu S. et al. Neonatal hypoxic ischemic encephalopathy-related biomarkers in serum and cerebrospinal fluid. Clin. Chim. Acta. 2015 Oct. 23(450). 282-297. DOI: 10.1016/j.cca.2015.08.021. PMID: 26320853.

Massaro A.N., Jeromin A., Kadom N., Vezina G. et al. Serum biomarkers of MRI brain injury in neonatal hypoxic ischemic encephalopathy treated with whole-body hypothermia: a pilot study. Pediatr. Crit. Care Med. 2013 Mar. 14(3). 310-317. DOI: 10.1097/PCC.0b013e3182720642. PMID: 23392373. PMCID: PMC4420174.

Massaro A.N., Wu Y.W., Bammler T.K. et al. Plasma Biomarkers of Brain Injury in Neonatal Hypoxic-Ischemic Encephalopathy. J. Pediatr. 2018 Mar. 194. 67-75. DOI: 10.1016/j.jpeds.2017.10.060. PMID: 29478510.

Moresco L., Bellissima V., Colivicchi M. et al. Markers of brain injure in non-invasive biological fluids. Minerva Pediatr. 2010. 62(3). 141-143. PMID: 21090084.

Mukhopadhyay D., Riezman H. Proteasome-independent functions of ubiquitin in endocytosis and signaling Scienc.e: journal. 2007 Jan 12 (315). 5809. 201-205. DOI: 10.1126/science.1127085. PMID: 17218518.

Paise F., Sargison R., Makwana N. et al. Changes in the sublingual microcirculation and endothelial adhesion mo-lecules during the course of severe meningococcal disease treated in the paediatric intensive care unit. Intensive. Care Med. 2012. 38(5). 863-871. DOI: 10.1007/s00134-012-2476-5. PMID: 22398755.

Petruzziello-Pellegrini T.N., Moslemi-Naeni M., Marsden P.A. New insights into Shiga toxin-mediated endothelial dysfunction in hemolytic uremic syndrome. Virulence. 2013 Aug. 4(6). 556-563. DOI: 10.4161/viru.26143. PMID: 23955166. PMCID: PMC5359733.

Schmidt E.P., Kuiebler W.M., Lee W.L. et al. Adhesion mo-lecules: master controllers of the circulatory system. Compr. Physiol. 2016. 6(2). 945-973. DOI: 10/1002/cphy.c150020.

Sergeeva V.A., Aleksandrovich Y.S., Petrenkova N.S. Predictors of hypoxic ischemic encephalopathy in newborns. Messenger of anesthesiology and resuscitation. 2017. 14(4). 16-22. DOI: 10.21292/2078-5658-2017-14-4-16-22.

Silveira R.C., Procianoy R.S. Levels of interleukin-6 and tumor necrosis factor-alpha in the cerebrospinal fluid of full-term newborns with hypoxic-ischemic encephalopathy. J. Pediatr. 2003. 143(5). 625-629. DOI: 10.1067/S0022-3476(03)00531-6. PMID: 14615734.

Stewart A., Tekes A., Huisman T.A., Jennings J.M. et al. Glial fibrillary acidic protein as a biomarker for periventricular white matter injury. Am. J. Obstet. Gynecol. 2013 Jul. 209(1). 27. е. 1-7. DOI: 10.1016/j.ajog.2013.02.049. PMID: 23467054. PMC3708978.

Van Laerhoven H., de Haan T.R., Offringa M. et al. Prognostic tests in term neonates with hypoxic-ischemic encephalopathy: a systematic review. Pediatrics. 2013 Jan. 131(1). 88-98. PMID: 23248219. DOI: 10.1542/ peds.2012-1297. PMID: 23248219.

Verkhratsky A., Butt A. Glial neurobiology: a textbook. England: John Wiley & Sons, Ltd. 2007. 209 р. DOI: 10.1002/9780470517796.

Wilkinson K.D. The discovery of ubiquitin-dependent proteo-lysis. Proc. Natl Acad. Sci. USA. 2005 Oct. 102(43). 15280-15282. DOI: 10.1073/pnas.0504842102. PMCID: PMC1266097. PMID: 16230621.

Yang X., Chang Y., Wei W. Endothelial disfunction and inflammation: immunity in rhemathoid arthritis. Mediators Inflamm. 2016. 681317. DOI: 10.1155/2016/6813016. PMID: 27122657. PMCID: PMC4829719.

Yoon B.H., Romero R., Park J.S. et al. The relationship among inflammatory lesions of the umbilical cord (funusitis), umbilical cord plasma interleukin 6 concentration, amniotic fluid infection, and neonatal sepsis. Am. J. Obstet. Gynecol. 2000 Nov. 183(5). 1124-1129. DOI: 10.1067/mob.2000.109035. PMID: 11084553.

Zamir E. Molecular complexity and dynamics of cell-matrix adhesions. J. Cell. Sci. 2001 Oct. 114(Pt 20). 3583-3590. PMID: 11707510.

Published

2021-03-10

Issue

Section

Review