Skip to main content
Log in

Structural Changes in the Elements of the Blood-Brain Barrier of the Hippocampus in Rats after Exposure to Perinatal Hypoxia and the Potential for Their Pharmacological Correction

  • Published:
Neuroscience and Behavioral Physiology Aims and scope Submit manuscript

Objectives. To study the dynamics of structural changes in elements of the blood-brain barrier of the hippocampus during the early postnatal period and subsequent ontogeny after exposure to perinatal hypoxia and to investigate the potential for pharmacological correction of these changes. Materials and methods. Experiments were performed on Wistar laboratory rats with a model of the encephalopathy of premature human infants using electron microscopy. Results. Perinatal hypoxia was followed by detection of structural damage to capillary walls: there were increases in the size of endotheliocytes, increases in the numbers of cytoplasmic processes, changes in the diameter of capillary lumens, and delays in the formation of the basal membrane. A marked endothelium-protecting effect was seen with the formulation Salifen at all study time points. Salifen was found to decrease the intensity of the reactions of elements of the blood-brain barrier to the harmful actions of perinatal hypoxia. Conclusions. Perinatal hypoxia has marked damaging effects on all elements of the blood-brain barrier of the hippocampus, the induced lesions being detected at both the early stages of postnatal development and in animals reaching adulthood. Use of Salifen immediately after exposure to perinatal hypoxia eliminated much of the structural damage to endotheliocytes and the basal membrane by the juvenile period. This study provides grounds for believing that the use of Salifen in ischemic brain injury in neonates has potential and our series of further preclinical studies will be continued.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. L. B. Ivanova, V. I. Karamysheva, V. N. Perfi lova, and I. N. Tyurenkov, “Effects of GABA derivatives on endothelium function in rats with experimental gestosis,” Probl. Reprodukts., No. 1, 28–30 (2012).

  2. A. V. Morgun, N. V. Kuvacheva, T. E. Taranushenko, et al., “Current concepts in the pathogenesis of perinatal ischemic injury to cells in neurovascular units in the brain: target molecules for neuroprotection,” Vestn. Ross. Akad. Med. Nauk., 68, No. 12, 26–35 (2013).

    Article  Google Scholar 

  3. N. E. Ordyan, V. K. Akulova, V. I. Mironova, and V. A. Otellin, “Perinatal hypoxia-induced behavioral impairments in juvenile rats and their correction with GABA derivatives,” Byull. Eksperim. Biol. Med., 164, No. 8, 140–144 (2017).

    Google Scholar 

  4. V. A. Otellin, L. I. Khozhai, L. A. Vataeva, and T. T. Shishko, “Delayed consequences of hypoxia in the perinatal period of development on structural-functional characteristics of the brain in rats,” Ros. Fiziol. Zh., 97, No. 10, 1092–1100 (2011).

    CAS  Google Scholar 

  5. V. A. Otellin, L. I. Khozhai, and I. N. Tyurenkov, “Effects of perinatal hypoxia on the structure of the blood-brain barrier in rats given Salifen,” Morfologiya, 148, No. 6, 34–37 (2015).

    CAS  Google Scholar 

  6. V. A. Otellin, L. I. Khozhai, and T. T. Shishko, “Reactions of the structural elements of the blood-brain barrier of neonatal rat pups to normobaric hypoxia,” Zh. Evolyuts. Biokhim. Fiziol., 51, No. 5, 377–382 (2015).

    CAS  Google Scholar 

  7. I. N. Tyurenkov, A. V. Voronkov, A. A. Slietsans, and E. V. Volotova, “Endothelium protectors – a new class of pharmacological agents,” Vestn. Ross. Akad. Med. Nauk., No. 7, 50–57 (2012).

  8. V. P. Chekhonin, V. P. Baklaushev, G. M. Yusubalieva, et al., “Basic applied aspects of studies of the blood-brain barrier,” Vestn. Ross. Akad. Med. Nauk., No. 8, 66–78 (2012).

  9. G. Distefano and A. D. Pratico, “Actualities on molecular pathogenesis and repairing processes of cerebral damage in perinatal hypoxic-ischemic encephalopathy,” Ital. J. Pediatr., 36, 63–73 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. A. W. Morris, M. M. Sharp, N. J. Albargothy, et al., “Vascular basement membranes as pathways for the passage of fluid into and out of the brain,” Acta Neuropathol., 131, No. 5, 725–736 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. F. Niu, X. Y. Song, J. F. Hu, et al., “IMM-H004, A new coumarin derivative, improved focal cerebral ischemia via blood-brain barrier protection in rats,” J. Stroke Cerebrovasc. Dis., 26, No. 10, 2065–2073 (2017).

    Article  PubMed  Google Scholar 

  12. A. E. Sifat, B. Vaidya, and T. J. Abbruscato, “Blood-brain barrier protection as a therapeutic strategy for acute ischemic stroke,” AAPS J., 19, No. 4, 957–972 (2017).

    Article  CAS  PubMed  Google Scholar 

  13. M. S. Thomsen, L. J. Routhe, and T. Moos, “The vascular basement membrane in the healthy and pathological brain,” J. Cereb. Blood Flow Metab., 37, No. 10, 3300–3317 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to V. A. Otellin.

Additional information

Translated from Morfologiya, Vol. 154, No. 4, pp. 7–12, July–August, 2018.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Otellin, V.A., Khozhai, L.I., Tyurenkov, I.N. et al. Structural Changes in the Elements of the Blood-Brain Barrier of the Hippocampus in Rats after Exposure to Perinatal Hypoxia and the Potential for Their Pharmacological Correction. Neurosci Behav Physi 49, 779–783 (2019). https://doi.org/10.1007/s11055-019-00801-4

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11055-019-00801-4

Keywords

Navigation