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Maintaining blood–brain barrier integrity: Pericytes perform better than astrocytes during prolonged oxygen deprivation
Author(s) -
Al Ahmad A.,
Gassmann M.,
Ogunshola O.O.
Publication year - 2009
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21638
Subject(s) - blood–brain barrier , microbiology and biotechnology , barrier function , paracrine signalling , homeostasis , biology , astrocyte , programmed cell death , chemistry , neuroscience , apoptosis , central nervous system , biochemistry , receptor
Abstract The blood–brain barrier (BBB), consisting of specialized endothelial cells surrounded by astrocytes and pericytes, plays a crucial role in brain homeostasis. Many cerebrovascular diseases are associated with BBB breakdown and oxygen (O 2 ) deprivation constitutes a critical factor that onsets its disruption. We investigated the impact of astrocytes and pericytes on brain endothelial cell permeability and survival during different degrees of O 2 deprivation. Prolonged exposure to 1% O 2 caused barrier breakdown and exposure to 0.1% O 2 dramatically accelerated disruption and induced cell death, mediated at least in part via caspase‐3 activation. Reoxygenation allowed only cells exposed to 1% O 2 to re‐establish barrier function. Notably co‐culture with astrocytes and pericytes substantially enhanced barrier function under normoxic conditions, and produced differential responses during O 2 deprivation. At 1% O 2 astrocytes partially maintained barrier integrity whereas pericytes accelerated its disruption in the short‐term, having positive effects only after prolonged exposure. Unexpectedly, at 0.1% O 2 pericytes were more effective than astrocytes in preserving barrier function although the protection afforded by both cells involved inhibition of caspase‐3 pathways. Furthermore, cell‐specific regulation of auto‐ and paracrine VEGF signaling pathways were also in part responsible for the differential modulation of barrier function. Our data suggests that cellular cross‐talk within the neurovascular unit is crucial for preservation of barrier integrity and that pericytes, not astrocytes, play a significant role during severe and prolonged O 2 deprivation. J. Cell. Physiol. 218: 612–622, 2009. © 2008 Wiley‐Liss, Inc.