Development of blood-brain barrier under the modulation of HIF activity in astroglial and neuronal cells in vitro

Ruzaeva V.A.1 , Morgun A.V.1, Khilazheva E.D.1, Kuvacheva N.V.1, Pozhilenkova E.A.1, Boitsova E.B.1, Martynova G.P.1, Taranushenko T.E.1, Salmina A.B.1

1. Voino-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk, Russia
Section: Experimental Study
DOI: 10.18097/PBMC20166206664      PubMed Id: 28026810
Year: 2016  Volume: 62  Issue: 6  Pages: 664-669
Barriergenesis is the process of maturation of the primary vascular network of the brain responsible for the establishment of the blood-brain barrier. It represents a combination of factors that, on the one hand, contribute to the process of migration and tubulogenesis of endothelial cells (angiogenesis), on the other hand, contribute to the formation of new connections between endothelial cells and other elements of the neurovascular unit. Astrocytes play a key role in barriergenesis, however, mechanisms of their action are still poorly examined. We have studied the effects of HIF-1 modulators acting on the cells of non-endothelial origin (neurons and astrocytes) on the development of the blood-brain barrier in vitro. Application of FM19G11 regulating expression of HIF-1 activity and GSI-1 suppressing gamma-secretase and/or proteasomal activity resulted in the elevated expression of thrombospondins and matrix metalloproteinases in the developing blood-brain barrier. However, it caused the opposite effect on VEGF expression thus promoting barrier maturation in vitro.
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Keywords: blood-brain barrier, barriergenesis, neurovascular unit, angiogenesis, HIF-1 modulators

Ruzaeva, V. A., Morgun, A. V., Khilazheva, E. D., Kuvacheva, N. V., Pozhilenkova, E. A., Boitsova, E. B., Martynova, G. P., Taranushenko, T. E., Salmina, A. B. (2016). Development of blood-brain barrier under the modulation of HIF activity in astroglial and neuronal cells in vitro. Biomeditsinskaya Khimiya, 62(6), 664-669.
This paper is also available as the English translation: 10.1134/S1990750817010085
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