CC BY
8
МЕДИЦИНСКИЕ НАУКИ
LABORATORY MARKERS OF PERINATAL HYPOXIC DAMAGE TO THE CENTRAL NERVOUS SYSTEM IN NEWBORNS Kudratova Z.E.1, Rustamova G.R.2, Kamedova F.S.3 Email: Kudratova 1174@scientifictext.ru
1Kudratova Zebo Erkinovna - Assistant, DEPARTMENT OF CLINICAL LABORATORY DIAGNOSIS; 2Rustamova Gulnoza Rustamovna - Assistant, DEPARTMENT OF № 3 PEDIATRIC AND MEDICAL GENETICS; 3Hamedova Farangiz Suratovna - Assistant, DEPARTMENT OF NEUROLOGY AND NEUROSURGERY, SAMARKAND STATE MEDICAL INSTITUTE, SAMARKAND, REPUBLIC OF UZBEKISTAN
Abstract: despite the introduction of new technologies that improve the outcome of newborns at high perinatal risk, the incidence of perinatal neurological complications in developed countries is currently not decreasing, moreover, about 40% of such disorders occur in premature newborns. Perinatal hypoxic lesions of the central nervous system (CNS) in newborns, the risk factors for which are intrauterine fetal hypoxia, asphyxia at birth, and postnatal extracerebral causes, constitute a significant part in the structure of perinatal cerebral lesions and significantly affect early childhood morbidity, disability and mortality.
Keywords: newborns, childhood morbidity, asphyxia, new laboratory markers.
ЛАБОРАТОРНЫЕ МАРКЕРЫ ПЕРИНАТАЛЬНЫХ ГИПОКСИЧЕСКИХ ПОВРЕЖДЕНИЙ ЦЕНТРАЛЬНОЙ НЕРВНОЙ СИСТЕМЫ
123
Кудратова З.Э. , Рустамова Г.Р. , Хамедова Ф.С.
1Кудратова Зебо Эркиновна - ассистент, кафедра клинической лабораторной диагностики;
2Рустамова Гулноза Рустамовна - ассистент, кафедра № 3 педиатрии и медицинской генетики; 3Хамедова Фарангиз Суратовна - ассистент, кафедра неврологии и нейрохирургии, Самаркандский государственный медицинский институт, г. Самарканд, Республика Узбекистан
Аннотация: несмотря на внедрение новых технологий, улучшающих исход новорожденных с высоким перинатальным риском, частота перинатальных неврологических осложнений в развитых странах в настоящее время не снижается, более того, около 40% таких нарушений возникает у недоношенных новорожденных. Перинатальные гипоксические поражения центральной нервной системы (ЦНС) у новорожденных, факторами риска которых являются внутриутробная гипоксия плода, асфиксия при рождении и послеродовые экстрацеребральные причины, составляют значительную часть в структуре перинатальных поражений головного мозга и существенно влияют на заболеваемость в раннем детстве, инвалидность и смертность.
Ключевые слова: новорожденные, детская заболеваемость, асфиксия, новые лабораторные маркеры.
UDC 616-009
In 15-20% of newborns with this pathology, such cerebral complications such as intracranial hemorrhage, cerebral ischemia (hypoxic-ischemic encephalopathy) and neuropsychological disorders. Modern methods of treatment can minimize damage to the central nervous system and accelerate the healing process of newborns with perinatal central nervous system damage. However, the difficulties of diagnosis make it difficult timely application of these methods and reduce their efficiency [14].
Over the past 20 years, for the diagnosis of hypoxic perinatal CNS lesion, various researchers have proposed many new laboratory markers: the content of hypoxanthine in the amniotic fluid, erythropoietin, lipid hydroperoxides and lactate in umbilical cord blood, etc [12, 15].
The review considers the diagnostic value of circulating biochemical markers of perinatal hypoxic damage CNS in newborns - xanthine, hypoxanthine, adrenomedullin [1, 5, 7].
Xanthine and hypoxanthine. With hypoxia, increased breakdown of ATP and increased concentration calcium ions in cells, the xanthine oxidase enzyme is activated, which is involved in the catabolism of purine nitrogenous bases. Xanthine oxidase catalyzes the conversion of xanthine to hypoxanthine and then to uric acid with the production of superoxide radical, which acts as an intermediate product [13].
High activity of xanthine oxidase, especially when hypoxia, found in the endothelium of the microvessels of the brain, therefore, increased production of superoxide radical and other active oxygen forms is one of the factors leading to damage the blood-brain barrier [15].
In this regard, it is believed that the accumulation of hypoxanthine and xanthine in the blood can serve as a laboratory sign of hypoxia and, possibly, perinatal damage to the central nervous system in newborns [1,4].
Investigated the diagnostic value determination of the concentration of xanthine and hypoxanthine in umbilical cord blood plasma of newborns with intraventricular hemorrhage, developed as a result of asphyxia [8].
At the diagnostic threshold for xanthine concentration equal to 0.99 mg / l, the sensitivity of this study as an indicator of intraventricular hemorrhage was 82%, the specificity was 79% [7, 9].
Activin A. Activin A glycoprotein consists of two subunits (Pa) and belongs to the superfamily transforming growth factor (TGf-P). Activin A and its receptors are expressed in brain tissues both during development and in the mature brain [3, 4].
Activin A production is stimulated by active forms of oxygen and an increase in intracellular concentration of calcium ions in neurons. CSF activin A concentrations were measured in healthy and full-term newborns with asphyxia, complicated by hypoxic-ischemic encephalopathy during the 1st week of life [1, 7]. CSF activin A levels in newborns with asphyxia were significantly higher than that of healthy people [2, 6].
Moreover, the most a high level of activin A was found in newborns with developing severe hypoxic ischemic encephalopathy, which, according to the researchers, indicates an increase in the synthesis of activin A in the central nervous system during hypoxia [1, 5, 10].
Protein S100B. Glia protein s100B belongs to the family of calcium-binding proteins, represented by homo- and heterodimers of a and p subunits: a-a, a-P, p-p.
S100b protein, highly specific for nervous tissue is a dimer of a-P and p-p. In the nervous tissue, this protein is found in the greatest amount in glial cells and some subpopulations of neurons. It has been shown that an increase in the concentration of ionized calcium in a neuron during excitatory toxicity induces protein synthesis and secretion s100B. Therefore, it was hypothesized that s100B protein may be useful as a marker of hypoxic brain damage [12, 13, 15].
In the perinatal period, increased concentrations of this protein in the blood are detected within 48-72 hours before the appearance of clinical, laboratory or ultrasound signs of intraventricular hemorrhage in premature infants and hypoxic ischemic encephalopathy in full-term infants [8, 12].
It should be borne in mind that from a clinical point of view it is desirable that the discussed biochemical markers satisfy several conditions: they reliably indicate damage to the central nervous system during the absence corresponding signs according to the results of neuroimaging studies or electroencephalography, provided a quantitative characteristic the extent and severity of brain
damage were useful in assessing the effectiveness of treatment and forecasting immediate and distant outcomes [6, 7, 15].
Maybe, to solve these problems, a combination of biochemical markers (multimarker) is required. Theoretically, laboratory detection of high risk of perinatal hypoxic lesions seems promising.
CNS in newborns, since individual proteins - laboratory marker candidates are involved in the development of adaptation to brain hypoxia-ischemia, their production stimulated by hypoxia, and therefore, it is possible identification of an increase in their level in biological fluids before the development of clinical and morphological disorders in the nervous system.
References / Список литературы
1. Adami C., Bianchi R., Pula G., Donato R. // Biochim. biophys. Acta, 2004. Vol. 1742. Р. 169.
2. Akturk A., Onal E. E, Atalay Y. et al. // J. matern. fetal neonatalmed., 2007. Vol. 20, n 7. Р. 521-525.
3. Allen M. A., Ferguson A. V. // Am. J. physiol., 1996. Vol. 270. Р. 920-925.
4. Blennow M., Savman K., llves P. et al. // Acta paediatr., 2001. Vol. 90, n 10. Р. 1171-1175.
5. Boldt T., Luukkainen P., Fyhrquist F. et al. // Acta paediatr., 1998. Vol. 87. № 1. Р. 93-94.
6. Botero D., Lifshitz F. // Curr. opin. pediatr., 1999. Vol. 11. № 4. Р. 340-347.
7. Bruns D.E., Huth E.J., MagidE., Young D.S. // Clin. chem. - 2000. Vol. 46. № 7. Р. 893-895.
8. Buonocore G., Perrone S., Longini M. et al. // Pediatr. res., 2002. Vol. 52. Р. 46-49.
9. Buonocore G., Perrone S. // Clin. perinatal., 2004. Vol. 31. № 1. Р. 107-116.
10. Castillo J., Rodriguez I. // Cerebrovasc. Dis., 2004. Vol. 17 (suppl. 1). Р. 7-18.
11. Celtik C., Acunas B., Oner N., Pala O. // Brain Dev., 2004. Vol. 26. Р. 398-402.
12. de Vroomen M., Takahashi Y., Gournay V. et al. // Pediatr. res., 1997. Vol. 41. Р. 493-497.
13. di lorio R., Marinoni E., LituaniaM. et al. // Clin. biochem., 2004. Vol. 37. Р. 1112-1116.
14. Drooge W. // physiol. rev., 2002. Vol. 82. - p. 47-95.
15. Ellis E.F., Willoughby K.A., Sparks S.A., Chen T. // J. neurochem. 2007. Vol. 101. Р. 1463.
