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(Circulation. 2004;110:1839-1846.)
© 2004 American Heart Association, Inc.

Stroke

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

From the Department of Molecular and Cellular Pharmacology (H.N., H.T., Y.N., T.T.), Mie University School of Medicine, Mie, and the Department of Neurosurgery (H.N., T.K.), University of Tokyo Graduate School of Medicine, Tokyo, Japan.

Correspondence to Toshio Tanaka, Professor, Molecular and Cellular Pharmacology, Mie University School of Medicine. 2-174, Edobashi, Tsu, Mie, 514-8507, Japan. E-mail tanaka{at}doc.medic.mie-u.ac.jp

Received December 31, 2002; de novo received December 21, 2003; revision received March 18, 2004; accepted April 15, 2004.

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.

Key Words: subarachnoid hemorrhage • vasospasm • brain • heat shock protein

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