Study of BDNF concentration dynamics in various brain structures in rats after exposure to acute normobaric hypoxia

Perinatal hypoxia is a significant problem that affects the development of the nervous system and subsequent cognitive functions in both humans and animals. In response to hypoxic exposure, the body produces trophic factors - neurotrophins, regulatory proteins that are synthesized in neurons and glia - NGF (nerve growth factor), BDNF (brain-derived neurotrophic factor), GDNF (glial cell-derived neurotrophic factor). BDNF supports differentiation, maturation and survival of neurons, and also exhibits a neuroprotective effect under adverse conditions such as glutamatergic stimulation, cerebral ischemia, hypoglycemia and neurotoxicity. The goal is to study the dynamics of BDNF concentration in various brain structures of rats after exposure to acute normobaric hypoxia.

Materials and Methods. The work was carried out on Wistar rats of both sexes (20 sexually mature females and 10 sexually mature males, which were equally divided into 2 groups by the randomization principle and from which the offspring were obtained). Group 1 was the control, and the state of premature human pregnancy was modeled for animals of Group 2: the effect of acute normobaric hypoxia on rat pups on the second postnatal day and subsequently the dynamics of BDNF concentration in the brain tissues, frontal cortex, hypothalamus and hippocampus of rat pups was assessed by the enzyme immunoassay method.

Results. It was found that acute normobaric hypoxia leads to an increase in BDNF concentration up to 7 days after exposure to hypoxia in the whole brain, frontal cortex, hypothalamus and hippocampus of rats of both sexes, and then the concentration of neutrophin decreases to the physiological norm. During the experiment, the concentration of BDNF in the whole brain of females was significantly lower than in males, and in the hippocampus – vice versa.

1. Fedotova N. N. Study of the influence of perinatal hypoxia on the physical and sensorimotor development of rat pups / N. N. Fedotova, O. N. Pavlova, O. N. Gulenko, V. V. Leonov, E. V. Lukenyuk // Modern issues of biomedicine. – 2025. – Vol. 9. –№ 1 (31). doi: 10.24412/2588-0500-2025_09_01_18.

2. Ordyan N. E. Disturbances in behavioral and hormonal stress responses of adolescent rats due to perinatal hypoxia and their correction by a new GABA derivative / N. E. Ordyan, V. K. Akulova, S. G. Pivina, V. A. Otellin, I. N. Tyurenkov // Journal of Evolutionary Biochemistry and Physiology. – 2019. – T. 55. – № 1. – P. 59–64. doi: 0.1134/S0044452919010091.

3. Piesova, M. Impact of perinatal hypoxia on the developing brain / M. Piesova, M. Mach // Physiological Research. – 2020. – Vol. 69. – P. 199–213. doi: 10.33549/physiolres.934198.

4. Gudasheva T. A. Dipeptide mimetic of nerve growth factor stimulates neurogenesis and synaptogenesis in the hippocampus and striatum of adult rats with focal cerebral ischemia / T. A. Gudasheva, P. Yu. Povarnina, A. A. Volkova, S. V. Kruglov, T. A. Antipova, S. B. Seredenin // Acta Naturae (Russian version). – 2019. – Vol. 11. – №3 (42). – P. 31–37. doi: 10.32607/20758251-2019-11-3-31-37.

5. Korobtsov A. V. Characteristics of neurotrophins and their localization in the neocortex of rats during acute experimental ischemia / A. V. Korobtsov, S. G. Kalinichenko, N. Yu. Matveeva // Bulletin of new medical technologies. Electronic publication. – 2018. – № 4. – P. 235–241. doi: 10.24411/2075-4094-2018-16130.

6. Berretta A. Poststroke recovery: the role of activity-dependent release of brain-derived neurotrophic factor / A. Berretta, Y. C. Tzeng, A. N. Clarkson // Expert Review of Neurotherapeutics. – 2014. – Vol. 14. – № 11. – P. 1335–1344. doi: 10.1586/14737175.2014.969242.

7. Bibel M. Biochemical and functional interactions between the neurotrophin receptors trk and p75(NTR) / M. Bibel, E. Hoppe, Y. A. Barde // EMBO Journal. – 1999. – Vol. 18. – № 3. – P. 616–622. doi: 10.1093/emboj/18.3.616.

8. Chen A. I. The neuroprotective roles of BDNF in hypoxic ischemic brain injury / A. I. Chen, L. J. Xiong, Y. U. Tong, M. Mao // Biomedical Reports. – 2013. – Vol. 1. – № 2. – P. 167–176. doi: 10.3892/br.2012.48.

9. Hu Y. BDNF and the diseased nervous system: a delicate balance between adaptive and pathological processes of gene regulation / Y. Hu, S.J. Russek // Journal of Neurochemistry. – 2008. – Vol. 105. – P. 1–17. doi: 10.1111/j.1471-4159.2008.05237.x.

10. Jiang Y. Intranasal brain-derived neurotrophic factor protects brain from ischemic insult via modulating local inflammation in rats / Y. Jiang, N. Wei, T. Lu, J. Zhu, G. Xu, X. Liu // Neuroscience. – 2011. – Vol. 172. – P. 398–405. doi: 10.1016/j.neuroscience.2010.10.054.

11. Stadlin A. Development of a postnatal 3-day-old rat model of mild hypoxic-ischemic brain injury / A. Stadlin, A. James, R. Fiscus, Y. F. Wong, M. Rogers, C. Haines // Brain Research. – 2003. – Vol. 993. – № 1–2. – P. 101–110. doi: 10.1016/j.brainres.2003.08.058.

12. Yang Z. Sustained neocortical neurogenesis after neonatal hypoxic/ischemic injury / Z. Yang, M. V. Covey, C. L. Bitel, L. Ni, G. M. Jonakait, S. W. Levison // Annals of Neurology. – 2007. – Vol. 61. – № 3. – P. 199–208. doi: 10.1002/ana.21068.

13. Wang H. Secretion of brain-derived neurotrophic factor from PC12 cells in response to oxidative stress requires autocrine dopamine signaling / H. Wang, G. Yuan, N. R. Prabhakar, M. Boswell, D. M. Katz // Journal of Neurochemistry. – 2006. – Vol. 96. – № 3. – P. 694–705. doi: 10.1111/j.1471-4159.2005.03572.x.

14. Kang H. Long-lasting neurotrophin-induced enhancement of synaptic transmission in the adult hippocampus / H. Kang, E. M. Schuman // Science. – 1995. – Vol. 267. – № 5204. – P. 1658–1662. doi: 10.1126/science.7886457.

15. Chen S. C. Novel molecular correlates of neuronal death and regeneration / S. C. Chen, H. D. Soares, J. I. Morgan // Advances in Neurology. – 1996. – Vol. 71. – P. 433–449.

16. Johansson B. B. Functional recovery after brain infarction / B. B. Johansson // Cerebrovascular Diseases. – 1995. – Vol. 5. – № 4. – P. 278–281. doi: 10.1111/j.1750-3639.1994.tb00814.x.

17. Golosnaya G. S. Vasculoendothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) in newborns with perinatal hypoxic lesions of the central nervous system / G. S. Golosnaya, S. A. Kotiy // Issues of modern pediatrics. – 2006. –№ 5. – P. 149.

18. Scheepens A. The effect of a global birth asphyxia on the ontogeny of BDNF and NGF protein expression in the juvenile brain / A. Scheepens, G. Wassink, C.E. Blanco // Developmental Brain Research. – 2003. – Vol. 140. – № 2. – P. 215–221. doi: 10.1016/s0165-3806(02)00608-9.

19. Pereira, L.O. Long-term effects of environmental stimulation following hypoxia-ischemia on the oxidative state and BDNF levels in rat hippocampus and frontal cortex / L. O. Pereira, P. M. Nabinger, A. C. P. Strapasson, P. Nardin, C. A. S. Gonçalves, I. R. Siqueira, C. A. Netto // Brain Research. – 2009. – Vol. 1247. – P. 188–195. doi: 10.1016/j.brainres.2008.10.017.

20. Diaz J. Therapeutic hypothermia provides variable protection against behavioral deficits after neonatal hypoxia-ischemia: a potential role for brain-derived neurotrophic factor / J. Diaz, S. Abiola, N. Kim, O. Avaritt, D. Flock, J. Yu, F. J. Northington, R. Chavez-Valdez // Developmental Neuroscience. – 2017. – Vol. 39. – № 1–4. – P. 257–272. doi: 10.1159/000454949.

21. Wang Z. Sodium hydrosulfide prevents hypoxia-induced behavioral impairment in neonatal mice / Z. Wang, J. Zhan, X. Wang, J. Gu, K. Xie, Q. Zhang, D. Liu // Brain Research. – 2013. – Vol. 1538. – P. 126–134. doi: 10.1016/j.brainres.2013.09.043.

22. Chavez-Valdez R. Sexual dimorphism in BDNF signaling after neonatal hypoxia-ischemia and treatment with necrostatin-1 / R. Chavez-Valdez, L. J. J. Martin, S. Razdan, E. B. B. Gauda, F. J. J. Northington // Neuroscience. – 2014. – Vol. 260. – P. 106–119. doi: 10.1016/j.neuroscience.2013.12.023.