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.
Keywords: Endothelial cell, heat shock protein, HSP25, HSPB1, microvessel, stroke, tight junction, vascular.
open access plus
Rights & PermissionsPrintExport