Potential Role for Heat Shock Protein 72 in Antagonizing Cerebral Vasospasm After Rat Subarachnoid Hemorrhage

Abstract

Background-Cerebral vasospasm can be defined as delayed-onset narrowing of the cerebral arteries that can occur after a spontaneous aneurysmal subarachnoid hemorrhage (SAH). Despite a large number of experimental and clinical investigations, the exact pathophysiology of vasospasm remains unknown. Using a fluorescence differential-display system, we have identified the gene encoding heat shock protein 72 (HSP72) as being highly upregulated by cerebral vasospasm. We therefore elucidated the role of the HSP72 gene in cerebral vasospasm in a rat experimental SAH model. Methods and Results-By angiography, cerebral vasospasm was detected from day 1, with maximal narrowing detected on day 2. Intracisternal injection of antisense HSP72 oligodeoxynucleotide led to specific inhibition of HSP72 gene expression and significantly aggravated cerebral vasospasm on days 2 and 3 of the angiographic studies. Oral administration of geranylgeranylacetone (GGA), an antiulcer drug, enhanced HSP72 induction and reduced cerebral vasospasm. Conclusions-These results suggest HSP72 plays a novel role in antagonizing delayed cerebral vasospasm after SAH and that GGA provides protective effects against delayed cerebral vasospasm, at least partly via induction of HSP72.

Inhibition of Nischarin Expression Attenuates Rilmenidine-Evoked Hypotension and Phosphorylated Extracellular Signal-Regulated Kinase 1/2 Production in the Rostral Ventrolateral Medulla of Rats

“…Furthermore, the antisense ODNs used in the present study were phosphorothioated to prevent their degradation by endogenous enzymes (Putney et al, 1981). The dose regimen of the antisense ODNs was based on reported studies (Satoh et al, 2002;Nikaido et al, 2004). We report a substantial (Ͼ80%) reduction in nischarin level in the RVLM of rats treated with nischarin antisense ODN.…”

Fundamental increase in pressure-dependent constriction of brain parenchymal arterioles from subarachnoid hemorrhage model rats due to membrane depolarization

“…Although rat models of SAH have been used widely to study the impact of subarachnoid blood on the brain and cerebral vasculature (37,46), caution should be used in extrapolating data obtained from rodents to SAH-induced pathologies observed in humans after cerebral aneurysm rupture. For example, pial artery vasospasm in SAH model rats is less severe and of shorter time course than reported in canine and primate SAH models or in many cases of SAH-induced vasospasm in humans (41,42).…”

HSP72 attenuates renal tubular cell apoptosis and interstitial fibrosis in obstructive nephropathy

“…It has been shown that HSP72 can protect a variety of cells, including renal tubule cells, from thermal, toxic, and ATP depletion-mediated injury in vitro (31,35,47). Enhanced HSP72 expression also ameliorates myocardial, liver, brain, and renal damage induced by ischemia-reperfusion, cyclosporin, and endotoxin exposure in rats (9,10,26,35). Our preliminary results (data not shown), as well as those reported by others, showed that after ureteric obstruction, increased HSP72 expression started at day 3, peaked at day 7, and was maintained over the following 14 days, which paralleled the progression of renal fibrosis (18,37).…”