http://www.ncbi.nlm.nih.gov/pubmed/23469858
Abstract
Loss of integrity
of the blood-brain barrier (BBB) in stroke victims initiates a
devastating cascade of events including extravasation of blood-borne
molecules, water, and inflammatory cells deep into brain parenchyma.
Thus, it is important to identify mechanisms by which BBB integrity can
be maintained in the face of ischemic injury in experimental stroke. We
previously demonstrated that the phylogenetically conserved small heat
shock protein 27 (HSP27) protects against transient middle cerebral
artery occlusion (tMCAO). Here we show that HSP27 transgenic
overexpression also maintains the integrity of the BBB in mice subjected
to tMCAO. Extravasation of endogenous IgG antibodies and exogenous
FITC-albumin into the brain following tMCAO was reduced in transgenic
mice, as was total brain water content. HSP27 overexpression abolished
the appearance of TUNEL-positive profiles in microvessel walls.
Transgenics also exhibited less loss of microvessel proteins following
tMCAO. Notably, primary endothelial cell cultures were rescued from
oxygen-glucose deprivation (OGD) by lentiviral HSP27 overexpression
according to four viability assays, supporting a direct effect on this
cell type. Finally, HSP27 overexpression reduced the appearance of
neutrophils in the brain and inhibited the secretion of five cytokines.
These findings reveal a novel role for HSP27 in attenuating
ischemia/reperfusion injury - the maintenance of BBB integrity.
Endogenous upregulation of HSP27 after ischemia in wild-type animals may
exert similar protective functions and warrants further investigation.
Exogenous enhancement of HSP27 by rational drug design may lead to
future therapies against a host of injuries, including but not limited
to a harmful breach in brain vasculature.
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