Abstract 10532: HSPA12B is a Novel Neuroprotective Heat Shock Protein Against Ischemic Stroke
Background: Stroke is the third leading cause of death in the United States. Recent evidence suggests that heat shock proteins (HSPs) serve as mediators of protection against cerebral ischemia/reperfusion (I/R)injury. HSPA12B is a newly discovered member of HSP70 family and is predominantly expressed in endothelial cells. HSPA12B has been shown to regulate angiogenesis and attenuate endotoxin-induced cardiac dysfunction. We hypothesized that HSPA12B is an important mediator that protects against focal cerebral I/R injury.
Methods: To critically evaluate our hypothesis, we induced focal cerebral ischemia by occlusion of the middle cerebral artery (60 min) followed by reperfusion (24 hrs) in transgenic mice overexpressing human HSPA12B (Tg, n=5) and age matched wild type littermates (WT, n=8). Infarct size was examined by triphenyltetrazolium chloride staining. The morphology of neurons in brain sections was examined by Nissl staining. Neurological deficits, blood-brain-barrier (BBB) permeability, and the expression of tight-junction proteins were also examined in the brain tissues after focal cerebral I/R.
Results: Infarct volume in HSPA12B Tg mice was significantly reduced by 61.5% compared with WT I/R mice. Morphologic examination showed that there was less neuronal damage in the hippocampus of Tg I/R mine compared with WT I/R mice. Tg mice showed preserved BBB function as evidenced by decreased leakage of Evans blue and significantly improved neurological score when compared with WT I/R mice. Western blot showed that the ratio of Bcl2/Bax was significantly increased and the levels of p-JNKs were markedly decreased in Tg I/R mice compared with WT I/R mice. In addition, Tg I/R mice showed increased expression of tight-junction proteins (ZO-1 and ZO-2) and the angiogenic factor, angiopoietin-1, compared with WT I/R mice.
Conclusions: Our data suggest that HSPA12B plays a protective role in focal cerebral I/R injury. The mechanisms involve preservation of BBB function and protection of neurons from I/R-induced injury. Upregulation of HSPA12B expression could result in a significant benefit for treatment and management of stroke patients.
- © 2011 by American Heart Association, Inc.