This Article Full Text Full Text (PDF) All Versions of this Article: 34/2/427    most recent 01.STR.0000053848.06436.ABv1 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 Borel, C. O. Articles by Bhardwaj, A. Search for Related Content PubMed PubMed Citation Articles by Borel, C. O. Articles by Bhardwaj, A. Pubmed/NCBI databases Substance via MeSH Related Collections Growth factors/cytokines Smooth muscle proliferation and differentiation Cerebral Aneurysm, AVM, & Subarachnoid hemorrhage

(Stroke. 2003;34:427.)
© 2003 American Heart Association, Inc.

Original Contributions

Possible Role for Vascular Cell Proliferation in Cerebral Vasospasm After Subarachnoid Hemorrhage

Cecil O. Borel, MD; Andy McKee, BSE; Augusto Parra, MD; Michael M. Haglund, MD, PhD; Amy Solan, MS; Vikas Prabhakar, MS; Huaxin Sheng, MD; David S. Warner, MD Laura Niklason, MD, PhD

From the Department of Anesthesiology (C.O.B., H.S., D.S.W., L.N.); the Division of Neurosurgery, Department of Surgery (C.O.B., M.M.H., D.S.W.); the Division of Neurology, Department of Medicine (A.P.); and the Department of Biomedical Engineering (A.M., A.S., V.P.), Duke University, Durham, NC.

Correspondence to Cecil O. Borel, MD, Department of Anesthesiology, Box 3094, Duke University Medical Center, Durham, NC 27710. E-mail borel001{at}mc.duke.edu

Background and Purpose— During vasospasm after subarachnoid hemorrhage (SAH), cerebral blood vessels show structural changes consistent with the actions of vascular mitogens. We measured platelet-derived vascular growth factors (PDGFs) in the cerebrospinal fluid (CSF) of patients after SAH and tested the effect of these factors on cerebral arteries in vivo and in vitro.

Methods— CSF was sampled from 14 patients after SAH, 6 patients not suffering SAH, and 8 normal controls. ELISA was performed for PDGF-AB, transforming growth factor-ß1, and vascular endothelial growth factor. A mouse model was used to compare cerebral vascular cell proliferation and PDGF staining in SAH compared with sham-operated controls. Normal human pial arteries were incubated for 7 days in vitro, 2 groups with human blood clot and 1 with and 1 without PDGF antibodies.

Results— PDGF-AB concentrations in CSF from SAH patients were significantly higher than those from non-SAH patients and normal controls, both during the first week after SAH and for all time points measured. Smooth muscle and fibroblast proliferation was observed after SAH in the mouse model, and this cellular replication was observed in conjunction with PDGF protein at the sites of thrombus. In human pial arteries, localized thrombus stimulated vessel wall proliferation, and proliferation was blocked by neutralizing antibodies directed against PDGFs.

Conclusions— Vascular mitogens are increased in the CSF of patients after SAH. Proliferation of cells in the vascular wall is associated with perivascular thrombus. Cellular proliferation and subsequent vessel wall thickening may contribute to the syndrome of delayed cerebral vasospasm.

Editorial Comment

Anish Bhardwaj, MD, Guest Editor

This article has been cited by other articles:

				G. H. Kim, D. K. Hahn, C. P. Kellner, Z. L. Hickman, R. J. Komotar, R. M. Starke, W. J. Mack, J. Mocco, R. A. Solomon, and E. S. Connolly Jr Plasma Levels of Vascular Endothelial Growth Factor After Treatment for Cerebral Arteriovenous Malformations Stroke, August 1, 2008; 39(8): 2274 - 2279. [Abstract] [Full Text] [PDF]

				L. H. Calabrese, D. W. Dodick, T. J. Schwedt, and A. B. Singhal Narrative Review: Reversible Cerebral Vasoconstriction Syndromes Ann Intern Med, January 2, 2007; 146(1): 34 - 44. [Abstract] [Full Text] [PDF]

				R. L. Macdonald, Z.-D. Zhang, M. Takahashi, E. Nikitina, J. Young, A. Xie, and L. Larkin Calcium sensitivity of vasospastic basilar artery after experimental subarachnoid hemorrhage Am J Physiol Heart Circ Physiol, June 1, 2006; 290(6): H2329 - H2336. [Abstract] [Full Text] [PDF]

				M. Yamaguchi-Okada, S. Nishizawa, M. Koide, and Y. Nonaka Biomechanical and phenotypic changes in the vasospastic canine basilar artery after subarachnoid hemorrhage J Appl Physiol, November 1, 2005; 99(5): 2045 - 2052. [Abstract] [Full Text] [PDF]

				H. Nikaido, H. Tsunoda, Y. Nishimura, T. Kirino, and T. Tanaka Potential Role for Heat Shock Protein 72 in Antagonizing Cerebral Vasospasm After Rat Subarachnoid Hemorrhage Circulation, September 28, 2004; 110(13): 1839 - 1846. [Abstract] [Full Text] [PDF]

				J. M. Simard, T. A. Kent, C. O. Borel, and L. Niklason Vascular Smooth Muscle Proliferation as a Target for Therapeutic Intervention * Response Stroke, August 1, 2003; 34 (8): e108 - e108. [Full Text] [PDF]

				C. O. Borel, A. McKee, A. Parra, M. M. Haglund, A. Solan, V. Prabhakar, H. Sheng, D. S. Warner, L. Niklason, and A. Bhardwaj Possible Role for Vascular Cell Proliferation in Cerebral Vasospasm After Subarachnoid Hemorrhage * Editorial Comment Stroke, February 1, 2003; 34(2): 427 - 433. [Abstract] [Full Text] [PDF]