Abstract
Pre-eclampsia, eclampsia, and acute intranatal hypoxia often lead to the development of perinatal hypoxic-ischemic lesions of the CNS. The disease-related structural changes are periventricular leukomalacia (PVL) and intraventricular hemorrhage (IVH). Hypoxic-ischemic lesions of the CNS in the perinatal period can result in hydrocephalus, microcephaly, infantile cerebral paralysis (ICP), epilepsy, and psychomotor retardation. It is not always possible to accurately evaluate the disease severity and make a prognosis using routine methods of clinical, instrumental, and laboratory examination. It has been proven that a perinatal hypoxic-ischemic lesion of the CNS is always accompanied by the alteration of blood-brain barrier (BBB) permeability; therefore, the neuron-specific proteins (NSPs) outside the brain may be considered as markers of a pathologic process. To date more than 120 NSPs, in particular the non-enzymatic Ca2+-binding NSP, non-enzymatic NSPs responsible for cell recognition and cell adhesion, contractile and cytoskeletal proteins in nerve tissue, regulatory and transport secreted NSPs, myelin proteins, and glial NSPs have more or less detailed descriptions. To evaluate the state of the blood-brain barrier, it is rational to use the most-studied proteins, which are markers for neurons and astrocytes. These are the glial fibrillary acidic protein (GFAP) and the neuron-specific enolase (NSE). They do not cross the BBB and practically cannot be determined in serum under normal conditions. When BBB permeability is compromised, NSPs penetrate into the peripheral blood and may be measured. Dynamic determination of NSPs in serum may be used to evaluate BBB resistance, to estimate the severity of a CNS lesion, and to determine the prognosis for children with a perinatal hypoxic-ischemic lesion of the CNS.
Similar content being viewed by others
References
Blinov, D.V., Epilepsiya i Paroksizmal’nye Sostoyaniya, 2011, vol. 2, pp. 28–33.
Blinov, D.V., Immunoenzymatic Analysis of Neuron-specific Antigens in the BBB Permeability Measurements in the Perinatal Hypoxic-ischemic Lesions of the CNS (Clinico-Experimental Investigation), Cand. Sci. (Med.) Dissertation, Moscow: 2004.
Blinov, D.V. and Sandukovskaya, S.I., Epilepsiya i Paroksizmal’nye Sostoyaniya, 2010, vol. 2, no. 4, pp. 12–22.
Blinov, D.V., Akusherstvo, Ginekologiya i Reproduktsiya, 2011, vol. 2, pp. 5–12.
Order of Ministry of Health and Social Development of Russia no. 1687, December 27, 2011.
Volpe, J.J., Neurology of the Newborn, Philadelphia, Pa: Saunders Elsevier, 2008.
Yakunin, Yu.A. and Perminov, V.S., Ros. Vest. Perinat. i Ped., 1993, vol. 38, no. 2, p. 20–24.
Klassifikatsiya posledstvii perinatal’nykh porazhenii nervnoi sistemy u novorozhdennykh. Metodicheskie rekomendatsii (Classification of Consequences of Perinatal Lesions of Nervous System in Newborns. Methodical Recommendations), 2005, RASPM.
Sehba, F.A., Hou, J., Pluta, R.M., and Zhang, J.H., Prog. Neurobiol., 2012, vol. 97, no. 1, pp. 14–37.
Sehba, F.A., Pluta, R.M., and Zhang, J.H., Mol. Neurobiol., 2011, vol. 43, no. 1, pp. 27–40.
Bradbury, M., The Concept of a Blood-Brain Barrier, New York: John Wiley & Sons, 1979.
Ashmarin, I.P. and Stukalov, P.V., Neirokhimiya (Neurochemistry), 1996.
Chekhonin, V.P., Dmitrieva, T.B., and Zhirkov, Yu.A., Immunokhimicheskii analiz neirospetsificheskikh antigenov (Immunoenzymatic Analysis of the Neuronspecific Antigens), Moscow, 2000.
Chekhonin, V.P., Lebedev, S.V., Blinov, D.V., Gurina, O.I., Semenova, A.V., Lazarenko, I.P., Petrov, S.V., Ryabukhin, I.A., Rogatkin, S.O., and Volodin, N.N., Voprosy Ginekologii, Akusherstva i Perinatologii, 2004, vol. 3, no. 2, pp. 50–56.
Eng, L.F., Ghirnikar, R.S., and Lee, Y.L., Neurochem. Res., nos. 9–10, pp. 1439–1451.
Chekhonin, V.P., Gurina, O.I., and Dmitrieva, T.B. Monoklonal’nye antitela k neirospetsificheskim belkam (The Monoclonal Antibodies to Neuron-specific Proteins), Moscow: Meditsina, 2007.
Siegel, G. and Schratt, G., Identification of Novel MicroRNA Regulatory Proteins in Neurons Using RNAi-Based Screening. http://www.sfn.org/siteobjects/published/3Schratt.pdf. Cited February 13, 2012.
Steinacker, P., Aitken, A., and Otto, M., Semin. Cell Dev. Biol., 2011, vol. 22, no. 7, pp. 696–704.
Einav, S., Kaufman, N., Algur, N., and Kark, J.D., J. Am. Coll. Cardiol, 2012, vol. 60, no. 4, pp. 304–311.
Palmio, J., Huuhka, M., Laine, S., Huhtala, H., Peltola, J., Leinonen, E., Suhonen, J., and Keranen, T., Psychiatry Res., vol. 177, nos. 1–2, pp. 97–100.
Shinozaki, K., Oda, S., Sadahiro, T., Nakamura, M., Abe, R., Nakada, T.A., Nomura, F., Nakanishi, K., Kitamura, N., and Hirasawa, H., Resuscitation, 2009, vol. 80, no. 8, pp. 870–875.
Streitbürger, D.P., Arelin, K., and Kratzsch, J., Thiery J., Steiner J., Villringer A., Mueller K., Schroeter M.L, PLoS One, 2012, vol. 7, no. 8, e43284.
Ngankam, L., Kazantseva, N.V., and Gerasimova, M.M., Zh. Nevrol. Psikhiatr. Im. S. S. Korsakova, 2011, vol. 111, no. 7, pp. 61–65.
Ennen, C.S., Huisman, T.A., Savage, W.J., Northington, F.J., Jennings, J.M., Everett, A.D., and Graham, E.M., Am. J. Obstet. Gynecol., 2011, vol. 205, no. 3, pp. 251–257.
Middeldorp, J. and Hol, E.M., Prog. Neurobiol., 2011, vol. 93, no. 3, pp. 421–433.
Schiff, L., Hadker, N., Weiser, S., and Rausch, C., Mol. Diagn. Ther., 2012, vol. 16, no. 2, pp. 79–92.
Ramaswamy, V., Horton, J., Vandermeer, B., Buscemi, N., Miller, S., and Yager, J., Pediatr. Neurol., 2009, vol. 40, no. 3, pp. 215–226.
Oh, S.H., Lee, J.G., Na, S.J., Park, J.H., Choi, Y.C., and Kim, W.J., Arch. Neurol., 2003, vol. 60, no. 1, pp. 37–41.
Paulus, W., Acta. Neuropathol., 2009, vol. 118, no. 5, pp. 603–604.
Thomberg, E., Thiringer, K., Hagberg, H., and Kjellmer, I., Arch. Dis. Child. Fetal. Neonatal., 1995, no. 72, pp. 39–42.
Kamphuis, W., Mamber, C., Moeton, M., Kooijman, L., Sluijs, J.A., Jansen, A.H., Verveer, M., de Groot, L.R., Smith, V.D., Rangarajan, S., Rodriguez, J.J., Orre, M., and Hol, E.M., PLoS One, 2012, vol. 7, no. 8, e42823.
Rai, A., Maurya, S.K., Sharma, R., and Ali, S., Toxicol. Mech. Methods, 2012. doi: 10.3109/15376516.2012.721809.
van den Berge, S.A., Middeldorp, J., Zhang, C.E., Curtis, M.A., Leonard, B.W., Mastroeni, D., Voorn, P., van de Berg, W.D., Huitinga, I., and Hol, E.M., Aging Cell, 2010, vol. 9, no. 3, pp. 313–326.
Di Domenico, F., Coccia, R., Butterfield, D.A., and Perluigi, M., 2011, vol. 1814, no. 12, pp. 1785–1795.
Mukhtarova, S.N., Meditsinskie Novosti Gruzii, 2010, vol. 4, no. 181, pp. 49–54.
Nagdyman, N., Kömen, W., Ko, H., Muller, C., and Obladen, M., Pediatric Research, 2001, vol. 49, no. 4, pp. 133–139.
Berger, R., Pierce, M., Wisnievski, S., Adelson, P., Clark, R., Ruppel, R., and Kochanek, P., Pediatrics, 2002, vol. 109, no. 2, pp. 34–38.
Clark, R., Kochalek, P., and Adelson, P., J. Pediatr., 2000, no. 137, pp. 197–204.
Elimian, A., Figueroa, R., Verma, U., Visintainer, P., Sehgal, P., and Tejani, N., Obst. Gynecol., 1998, vol. 92, no. 1, pp. 546–555.
Garcia-Alix, A., Cabanas, F., Pellicer, A., Hernanz, A., Stiris, T.A., and Quero, J., Pediatrics, 1994, no. 93, pp. 234–240.
Blennow, M., Savman, K., Ilves, P., Thoresen, M., and Rosengren, L., Acta. Paediatr., 2001, no. 90, pp. 1171–1175.
Greishen, G., Biol. Neonate, 1992, no. 62, pp. 243–247.
Levene, M., Biol Neonate, 1992, no. 62, pp. 248–251.
Author information
Authors and Affiliations
Corresponding author
Additional information
Original Russian Text © D.V. Blinov, A.A. Terent’ev, 2013, published in Neirokhimiya, 2013, Vol. 30, No. 1, pp. 22–28.
Rights and permissions
About this article
Cite this article
Blinov, D.V., Terent’ev, A.A. Protein markers of hypoxic-ischemic lesions of the CNS in the perinatal period. Neurochem. J. 7, 16–22 (2013). https://doi.org/10.1134/S1819712413010029
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S1819712413010029