Neuroscience and Behavioral Physiology

, Volume 33, Issue 6, pp 607–611

The Effects of Ante- and Postnatal Hypoxia on the Central Nervous System and Their Correction with Peptide Hormones

  • M. V. Maslova
  • A. S. Maklakova
  • N. A. Sokolova
  • I. P. Ashmarin
  • E. N. Goncharenko
  • Ya. V. Krushinskaya


Ante- and postnatal hypoxia significantly worsened the postnatal development of animals. The posthypoxic behavioral model included hyperactivity and decreased learning ability, these being typical manifestations of attention deficit disorder. A peptide constellation prevented and significantly improved posthypoxic postnatal development and eliminated the majority of negative behavioral changes.

ante- and postnatal hypoxia CNS peptidergic correction 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    I. P. Ashmarin, V. V. Gavryushov, V. Yu. Ionidi, et al., “Thyroliberin normalizes cerebral circulation and pO2 in neonates,” Dokl. Akad. Nauk SSSR, 312, No. 1, 214–244 (1990).Google Scholar
  2. 2.
    I. P. Ashmarin and M. F. Obukhova, “Regulatory peptides, a functionally continuous population,” Biokhimiya, 51, No. 4, 3–8 (1986).Google Scholar
  3. 3.
    I. P. Ashmarin and S. A. Chepurnov, “Thyroliberin, melanostatin, and their analogs - neurophysiological basis of expanded clinical use,” in: Neuroendicrinological Aspects of Current Endocrinology [in Russian], Moscow (1991), p. 7.Google Scholar
  4. 4.
    I. P. Ashmarin, I. E. Gurskaya, and A. A. Guseva, “Thyroliberin: new physiological effects and potential for clinical use,” Vestn. RAMN, No. 6, 40–44 (1992).Google Scholar
  5. 5.
    I. P. Ashmarin, Neurophysiology [in Russian], Institute of Biomedical Chemistry Press, Russian Academy of Medical Sciences, Moscow (1996).Google Scholar
  6. 6.
    I. P. Ashmarin, V. N. Nezavibatko, I. F. Myasoedov, A. A. Kamenskii, I. A. Grivenkov, M. A. Ponomareva-Stepnaya, L. A. Andreeva, A. Ya. Kaplan, V. B. Koshelev, and T. V. Ryasina, “The nootropic adrenocorticotropin 4-10 analog Semax. Fifteen years of experience in the development of studies,” Zh. Vyssh. Nerv. Deyat., 47, No. 2, 420–429 (1997).Google Scholar
  7. 7.
    P. V. Balan, A. S. Maklakova, Ya. V. Krushinskaya, N. A. Sokolova, and Yu. B. Kudashov, “Delayed effects of acute hypobaric hypoxia in neonatal rats of different ages: the effects of the genopeptide Semax (ACTH4-7-PGP),” Akusherstvo i Ginekologiya, No. 1, 46–49 (1999).Google Scholar
  8. 8.
    N. A. Bastrikova, I. S. Novoderzhavina, A. A. Kamenskii, N. A. Sokolova, V. L. Kozhura, and I. P. Ashmarin, “The effects of hemorrhagic shock on learning processes in the delayed posthypoxic period,” Byull. Éksperim. Biol. Med., 1289, No. 12, 130–133 (1998).Google Scholar
  9. 9.
    E. O. Bragin and V. V. Yasentsov, “Opioid and monoamine mechanisms of regulation of body functions in extreme conditions,” in: Science and Technology [in Russian], All-Union Institute of Scientific and Technical Information (VINITI), Human and Animal Physiology Series (1991), Vol. 47.Google Scholar
  10. 10.
    I. G. Vlasova, N. E. Chepurnova, E. V. Efimova, S. A. Chepurnov, and I. P. Ashmarin, “Thyroliberin - long-lasting antihypoxic action,” Fiziol. Cheloveka, 49, No. 3, 107–109 (1994).Google Scholar
  11. 11.
    V. A. Voinov, N. I. Losev, and V. M. Bulaev, “The effects of naloxone and thyroliberin on respiration in conditions of acute hypoxia,” Byull. Éksperim. Biol. Med., No. 10, 408–410 (1984).Google Scholar
  12. 12.
    V. A. Voinov, N. I. Losev, and N. B. Romadanova, “Inspiratory stimulating effects of thyroliberin in conditions of acute respiratory hypoxia,” in: Proceedings of All-Union Scientific Conference, “Reactivity and Resistance. Fundamental and Applied Questions” [in Russian], Kiev (1987), p. 172.Google Scholar
  13. 13.
    E. N. Goncharenko, S. V. Antonova, S. V. Shestakova, M. Ya. Akhlaya, P. V. Balan, A. S. Maklakova, Ya. V. Krushinskaya, N. A. Sokolova, and I. P. Ashmarin, “Functional and biochemical characteristics of acute hypobaric hypoxia in neonatal and adult rats,” Akusherstvo i Ginekologiya, No. 3, 51–53 (1999).Google Scholar
  14. 14.
    V. A. Dubynin, N. Yu. Zemskaya, Yu. A. Ivleva, A. A. Kamenskii, S. V. Shestakova, I. V. Malinovskaya, E. N. Goncharenko, L. A. Andreeva, and N. F. Myasoedov, “Delayed effects of β-casomorphin-7 chronically administered to neonatal white rats,” Dokl. Ros. Akad. Nauk., 364, No. 6, 839–842 (1999).Google Scholar
  15. 15.
    E. V. Efimova S. A. Cherpurnov, and N. E. Chepurnova, “Immediate and delayed effects of thyroliberin given intranasally to humans,” in: Principles and Mechanisms of Activity of the Human Brain [in Russian], Leningrad (1989), p. 248.Google Scholar
  16. 16.
    T. P. Zhukova, E. I. Znamenskaya, and N. G. Palenova, Structural Changes in the Brain. Perinatal Pathology [in Russian], Meditsina, Moscow (1984).Google Scholar
  17. 17.
    V. Yu. Ionidi, A. B. Dulenkov, I. P. Ashmarin, S. A. Chepurnov, and N. E. Chepurnova, Thyroliberin - Antagonistic Actions and Normalization of Cerebral Circulation in the Clinical Resuscitation of Neonates. Collection of Reports [in Russian], Moscow, Vo. 20, pp. 52–53 and 75-76 (1991).Google Scholar
  18. 18.
    V. B. Koshelev, I. Yu. Belov, and N. A. Sokolova, “Antihypoxic actions of a number of endogenous regulatory peptides,” in: Proceedings of Conference “Summaries and Perspectives” [in Russian], St. Petersburg (1994), No. 1, p. 51.Google Scholar
  19. 19.
    A. S. Maklakova, A. A. Kamenskii, L. A. Alfeeva, N. G. Levitskaya, N. F. Nezavibat'ko, and I. P. Ashmarin, “Behavioral effects of β-casomorphin-7 and its des-Tyr analogs,” Byull. Éksperim. Biol. Med., No. 8, 155–158 (1993).Google Scholar
  20. 20.
    A. S. Maklakova, A. A. Kamenskii, L. A. Alfeeva, I. V. Nazarenko, and N. F. Nezavibat'ko, “The effects of β-casomorphin-7 on the level of food-related and defensive motivation in different types of learning,” Zh. Vyssh. Nerv. Deyat., 45, No. 6, 1143–1150 (1995).Google Scholar
  21. 21.
    A. S. Maklakova, The Neurotropic Effects of a Milk β-Casein Fragment, the Heptapeptide β-Casomorphin-7 [in Russian], Author's abstract of dissertation, Moscow State University Press, Moscow (1996).Google Scholar
  22. 22.
    M. V. Maslova, A. S. Maklakova A. V. Graf, N. A. Sokolova, I. P. Ashmarin, N. Yu. Kudryashova, Ya. V. Krushinskaya, E. N. Goncharenko, and S. V. Shestakova, “Brain bioamines and the behavior of offspring after antenatal hypoxia: effects of peptide neuromodulators,” Neirokhimiya (in press).Google Scholar
  23. 23.
    M. V. Maslova, A. S. Maklakova, M. V. Shkol'nikov, K. S. Zemlyanskii, and N. A. Sokolova, “The effects of prenatal acute hypobaric hypoxia on the behavioral responses of neonatal rats,” in: Fifth All-Russian Conference “Human Developmental Physiology,” Celebrating the 55th Anniversary from the Foundation of the Institute [in Russian], Moscow (2000), pp. 303–304.Google Scholar
  24. 24.
    M. A. Ponomareva-Stepnaya, V. N. Nezavibat'ko, L. V. Antonova, L. A. Andreeva, L. Yu. Alfeeva, V. N. Potamin, A. A. Kamenskii, and I. P. Ashmarin, “An analog of ACTH4-10 - a long-acting learning stimulator,” Khim. Farm. Zh., No. 7, 790–795 (1984).Google Scholar
  25. 25.
    Ts. V. Serbenyuk, I. E. Gurskaya, and A. D. Salyuta, “Restoration of impaired respiratory activity in cats by thyroliberin,” Byull. Éksperim. Biol. Med., 106, No. 7, 17 (1990).Google Scholar
  26. 26.
    A. B. Sorokin, N. N. Zavadenko, A. S. Petrukhin, N. L. Gorbachevskaya, N. G. Manelis, N. V. Grigor'eva, and N. Yu. Suvorina, “Attention deficit with hyperactivity in children: results of a multidisciplinary study,” in: Proceedings of the First International Conference in Memory of A. R. Luriya [in Russian], Moscow (1997), p. 37.Google Scholar
  27. 27.
    É. A. Édel'shtein, Perinatal Hypoxic Neurological Syndromes [in Russian], TsOLIUV Press, Moscow (1998).Google Scholar
  28. 28.
    I. P. Ashmarin, V. N. Nazavibatko, N. G. Levitskaya, V. B. Koshelev, and A. A. Kamensky, “Design and investigation of an ACTH(4-10) analogue lacking D-amino acids and hydrophobic radicals,” Neurosci. Res. Commun., 16, No. 2, 105–112 (1995).Google Scholar
  29. 29.
    V. Brantl, H. Techemacher, A. Henschen, and F. Lottspeich, “Novel opioid peptides derived from casein (β-casomorphins). I. Isolation from bovine casein peptone,” Hoppe-Seyler's Z. Physiol. Chem., 360, 1211–1216 (1979).Google Scholar
  30. 30.
    M. Dambska, D. Maslinska, and I. Kuchna, Neuropatol. Pol., 30, No. 3-4, 245–253 (1992).Google Scholar
  31. 31.
    A. I. Faden, T. P. Jacobs, and J. W. Holaday, “Opiate antagonist in neurologic recovery after spinal injury,” Science, 211, 493–494 (1981).Google Scholar
  32. 32.
    A. I. Faden, T. P. Jacobs, and J. W. Holaday, “Thyrotropin-releasing hormone improves neurologic recovery after spinal trauma in cats,” New Eng. J. Med., 305, 1063–1067 (1981).Google Scholar
  33. 33.
    M. T. Lin, H. K. Chan, C. F. Chen, and G. W. Teh, “Involvement of both opiate and catecholaminergic receptors in the behavioral excitation provoked by thryotropin-releasing hormone,” Neuropharmacol., 22, 463–469 (1983).Google Scholar
  34. 34.
    L. Nordstrom and S. Arulkumaran, “Intrapartum fetal hypoxia and biochemical markers: a review,” Obstet. Gynecol. Surv., 53, No. 10, 645–657 (1998).Google Scholar
  35. 35.
    C. Nyakas, B. Buwalda, R. J. Kramers, J. Traber, and P. G. Luiten, “Postnatal development of hippocampal and neocortical cholinergic and serotoninergic innervations in rat: effects of nitrite-induced prenatal hypoxia and nimodipine treatment,” Neurosci., 59, No. 3, (1994).Google Scholar
  36. 36.
    C. Nyakas, B. Buwalda, and P. G. Luiten, “Hypoxia and brain development,” Progr. Neurobiol., 49, No. 1, 1–51 (1996).Google Scholar
  37. 37.
    A. Pasi, H. Mahler, N. Lansel, C. Bernasconi, and F. Messiha, “β-Casomorphin-imunoreactivity in the brain stem of the human infant,” Res. Commun. Chem. Pathol. Pharmacol., 80, 305–322 (1993).Google Scholar
  38. 38.
    T. A. Slotkin, J. L. Saleh, E. C. McCook, and F. J. Seidler, “Impaired cardiac function during postnatal hypoxia in rats exposed to nicotine prenatally: implications for perinatal morbidity and mortality, and for sudden infant death syndrome,” Teratology, 55, No. 3, 177–184 (1997).Google Scholar
  39. 39.
    R. C. Vannucci, “Hypoxic-ischemic encephalopathy,” Amer. J. Perinatol., 17, No. 3, 113–120 (2000).Google Scholar

Copyright information

© Plenum Publishing Corporation 2003

Authors and Affiliations

  • M. V. Maslova
    • 1
  • A. S. Maklakova
    • 1
  • N. A. Sokolova
    • 1
  • I. P. Ashmarin
    • 1
  • E. N. Goncharenko
    • 1
  • Ya. V. Krushinskaya
    • 1
  1. 1.Faculty of BiologyM. V. Lomonosov Moscow State UniversityMoscowRussia

Personalised recommendations