This Article Full Text Full Text (PDF) All Versions of this Article: 35/7/1750    most recent 01.STR.0000129898.68350.9fv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yamaguchi, M. Articles by Zhang, J. H. Search for Related Content PubMed PubMed Citation Articles by Yamaguchi, M. Articles by Zhang, J. H. Related Collections Animal models of human disease Acute Cerebral Hemorrhage Cerebral Aneurysm, AVM, & Subarachnoid hemorrhage Other Stroke Treatment - Medical Aneurysm, AVM, hematoma

(Stroke. 2004;35:1750.)
© 2004 American Heart Association, Inc.

Original Contributions

Ras Protein Contributes to Cerebral Vasospasm in a Canine Double-Hemorrhage Model

Mitsuo Yamaguchi, MD; Changman Zhou, MD, PhD; Anil Nanda, MD, FACS John H. Zhang, MD, PhD

From the Department of Neurosurgery, Louisiana State University Health Sciences Center at Shreveport, Louisiana.

Correspondence to Dr John H. Zhang, Department of Neurosurgery, Louisiana State University Health Sciences Center at Shreveport, 1501 Kings Hwy, PO Box 33932, Shreveport, LA 71130-3932. E-mail johnzhang3910{at}yahoo.com

Background and Purpose— Mitogen-activated protein kinase (MAPK) has been shown to be involved in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). In the present study we examined the role of Ras protein, an upstream regulator of MAPK, and the effects of the inhibitors of Ras farnesyltransferase (FTase), FTI-277 and FTase inhibitor I, on angiographic vasospasm and clinical evaluations.

Methods— Twenty-five dogs were randomly divided into 5 groups: control, SAH, SAH+dimethyl sulfoxide, SAH+FTI-277, and SAH+FTase inhibitor I. An established canine double-hemorrhage model of SAH was used by injecting autologous arterial blood into the cisterna magna on days 0 and 2. Angiography was performed at days 0 and 7. Clinical behavior and the activation of Ras (GTP-Ras) and phosphorylated ERK1/2 of MAPK in the basilar arteries were examined.

Results— Severe vasospasm was obtained in the SAH and SAH+dimethyl sulfoxide dogs (42.5±2.5% and 38.9±2.4%, respectively). Enhanced GTP-Ras and phosphorylated ERK1/2 were observed in the spastic basilar arteries (P<0.05). Inhibitors of Ras FTase decreased GTP-Ras and phosphorylated ERK1/2, attenuated angiographic vasospasm, and improved appetite and activity scores.

Conclusions— Ras contributes to cerebral vasospasm, and inhibitors of Ras FTase may have potential in the management of cerebral vasospasm.

Key Words: vasospasm, intracranial • MAP kinase • ras proteins • subarachnoid hemorrhage

This article has been cited by other articles:

				K. Takeuchi, N. Miyata, M. Renic, D. R. Harder, and R. J. Roman Hemoglobin, NO, and 20-HETE interactions in mediating cerebral vasoconstriction following SAH Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2006; 290(1): R84 - R89. [Abstract] [Full Text] [PDF]

				K. Takeuchi, M. Renic, Q. C. Bohman, D. R. Harder, N. Miyata, and R. J. Roman Reversal of delayed vasospasm by an inhibitor of the synthesis of 20-HETE Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H2203 - H2211. [Abstract] [Full Text] [PDF]

				H. Yatsushige, M. Yamaguchi, C. Zhou, J. W. Calvert, and J. H. Zhang Role of c-Jun N-Terminal Kinase in Cerebral Vasospasm After Experimental Subarachnoid Hemorrhage Stroke, July 1, 2005; 36(7): 1538 - 1543. [Abstract] [Full Text] [PDF]