This Article Full Text Full Text (PDF) 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 Satoh, M. Articles by Macdonald, R. L. Search for Related Content PubMed PubMed Citation Articles by Satoh, M. Articles by Macdonald, R. L. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB 2-AMINOBENZAMIDE Related Collections Animal models of human disease Cerebral Aneurysm, AVM, & Subarachnoid hemorrhage Other Stroke Treatment - Medical Other Vascular biology

(Stroke. 2001;32:225.)
© 2001 American Heart Association, Inc.

Original Contributions

Inhibition of Poly(ADP-Ribose) Polymerase Attenuates Cerebral Vasospasm After Subarachnoid Hemorrhage in Rabbits

Motoyoshi Satoh, MD; Isao Date, MD; Masaaki Nakajima, MD; Kenji Takahashi, MD; Keiichi Iseda, MD; Takashi Tamiya, MD; Takashi Ohmoto, MD; Yoshifumi Ninomiya, MD, PhD Shoji Asari, MD

From the Departments of Neurological Surgery (M.S., I.D., M.N., K.T., K.I., T.T., T.O.), Molecular Biology and Biochemistry (Y.N.), and Faculty of Health Sciences (S.A.), Okayama University Medical School (Japan).

Correspondence to Isao Date, MD, Department of Neurological Surgery, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. E-mail idate333{at}med.okayama-u.ac.jp

Background and Purpose—Poly(ADP-ribose) polymerase (PARP) is important in modulating inflammation, which has been implicated in cerebral vasospasm after subarachnoid hemorrhage (SAH). We investigated the role of PARP in vasospasm using 3-aminobenzamide (3-AB), a PARP inhibitor, in a rabbit model.

Methods—Twenty-four New Zealand White rabbits were divided into 4 groups: (1) no treatment (control group, n=6); (2) blood injection without pretreatment (SAH-only group, n=6); (3) blood injection with pretreatment by vehicle (SAH+vehicle group, n=6); and (4) blood injection with pretreatment by 3-AB (SAH+3-AB group, n=6). We used the single-hemorrhage model of SAH, injecting autologous arterial blood into the cisterna magna. Angiography was performed before (baseline) and after (day 2) SAH, and the diameter of the basilar artery (BA) was measured. Animals were euthanatized after the second angiogram. After perfusion and fixation, the brains were cut into sections for hematoxylin and eosin and immunohistochemical staining for poly(ADP-ribosyl)ation.

Results—In the control group, there were no differences in the BA lumen caliber between baseline and day 2 (96.8±10.4%). Cerebral vasospasm in the SAH+3-AB group (88.2±6.2%) was remarkably attenuated in comparison with that in the SAH-only group (64.9±8.0%) and the SAH+vehicle group (65.6±10.8%). The BA in the SAH+3-AB group showed less corrugation of the tunica elastica interna than that in the SAH-only and SAH+vehicle groups. Staining for poly(ADP-ribosyl)ation was markedly inhibited in smooth muscle and adventitial cells of the BA in the SAH+3-AB group compared with other groups.

Conclusions—Inhibiting ADP-ribosylation attenuates cerebral vasospasm after SAH in rabbits, and PARP activation may play an important role in the development of cerebral vasospasm.

Editorial Comment

R. Loch Macdonald, MD, PhD, Guest Editor

Section of Neurosurgery, University of Chicago Medical Center, Chicago, Illinois

This article has been cited by other articles:

				D. Zemke, M. U Farooq, A. Mohammed Yahia, and A. Majid Delayed ischemia after subarachnoid hemorrhage: result of vasospasm alone or a broader vasculopathy? Vascular Medicine, August 1, 2007; 12(3): 243 - 249. [Abstract] [PDF]

				M. M. Monick, K. Cameron, J. Staber, L. S. Powers, T. O. Yarovinsky, J. G. Koland, and G. W. Hunninghake Activation of the Epidermal Growth Factor Receptor by Respiratory Syncytial Virus Results in Increased Inflammation and Delayed Apoptosis J. Biol. Chem., January 21, 2005; 280(3): 2147 - 2158. [Abstract] [Full Text] [PDF]

				L. Wang, J. X. Shi, H. X. Yin, C. Y. Ma, and Q. R. Zhang The Influence of Subarachnoid Hemorrhage on Neurons: An Animal Model Ann. Clin. Lab. Sci., January 1, 2005; 35(1): 79 - 85. [Abstract] [Full Text] [PDF]

				A. H. Boulares, A. J. Zoltoski, Z. A. Sherif, P. Jolly, D. Massaro, and M. E. Smulson Gene Knockout or Pharmacological Inhibition of Poly(ADP-Ribose) Polymerase-1 Prevents Lung Inflammation in a Murine Model of Asthma Am. J. Respir. Cell Mol. Biol., March 1, 2003; 28(3): 322 - 329. [Abstract] [Full Text] [PDF]

				Y. Watanabe, Y. Chu, J. J. Andresen, H. Nakane, F. M. Faraci, and D. D. Heistad Gene Transfer of Extracellular Superoxide Dismutase Reduces Cerebral Vasospasm After Subarachnoid Hemorrhage Stroke, February 1, 2003; 34(2): 434 - 440. [Abstract] [Full Text] [PDF]

				L. Virag and C. Szabo The Therapeutic Potential of Poly(ADP-Ribose) Polymerase Inhibitors Pharmacol. Rev., September 1, 2002; 54(3): 375 - 429. [Abstract] [Full Text] [PDF]