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J Cell Physiol. 2009 Mar;218(3):612-22. doi: 10.1002/jcp.21638.

Maintaining blood-brain barrier integrity: pericytes perform better than astrocytes during prolonged oxygen deprivation.

Author information

1
Institute of Veterinary Physiology and Zurich Centre for Integrative Human Physiology, University of Z├╝rich, Zurich, Switzerland.

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.

PMID:
19016245
DOI:
10.1002/jcp.21638
[Indexed for MEDLINE]

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