Changes in the Permeability and Expression of Markers of the Structural and Functional Integrity of the Blood–Brain Barrier under Early Postnatal Hypoxia in vivo

Abstract

Pathologies associated with perinatal exposure of the CNS to damaging factors, including hypoxia, are a serious problem. However, the mechanisms by which they influence the development of brain damage have been insufficiently studied. The purpose of this study is to analyze the BBB permeability and expression of markers of its structural and functional integrity in animals with hypoxia (rats subjected to hypoxia at the age of P7) at the early (1 hour after the hypoxia) and delayed (P28) periods of their development. In sections of the rat brains, we immunohistochemically evaluated the expression of HIF-1 and Rac1; the Evans blue dye content was measured by the photometric method in the brain homogenates. In animals subjected to hypoxia, BBB permeability increased, CD31 expression was reduced, RAC1 expression increased, HIF-1-positive cells were retained in the hippocampus mainly at the early stage of development; CD31 and RAC1 expression was suppressed during the delayed period of development. The most-pronounced brain damage at the age of P7 corresponds to changes in the structural and functional integrity and permeability of the BBB; the recovery of a neurological deficit and the permeability of the BBB (at the age of P28) under damage to the brain corresponds to the period of reparative angiogenesis, as well as manifestations of HIF-1 effects in endothelial cells and astrocytes in the cortex and limbic system.