title: Multiplexed protein profiling after aneurysmal subarachnoid hemorrhage: characterization of differential expression patterns in cerebral vasospasm.
abstract: Cerebral vasospasm is a major contributor to delayed morbidity following aneurysmal subarachnoid hemorrhage. We sought to evaluate differential plasma protein levels across time in patients with aneurysmal subarachnoid hemorrhage to identify potential biomarkers and to better understand the pathogenesis of cerebral vasospasm. Nine female patients with aneurysmal subarachnoid hemorrhage underwent serial analysis of 239 different serum protein levels using quantitative, multiplexed immunoassays (DiscoveryMAP 250+ v2.0, Myriad RBM, Austin, TX, USA) on post-hemorrhage days 0 and 5. A repeated measures analysis of variance determined that mean protein concentration decreased significantly in patients who developed vasospasm versus those who did not for alpha-2-macroglobulin (F [1.00,7.00]=16.33, p=0.005), angiogenin (F [1.00,7.00]=7.65, p=0.028), apolipoprotein A-IV (F [1.00,7.00]=6.308, p=0.040), granulocyte colony-stimulating factor (F [1.00,7.00]=9.08, p=0.020), macrophage-stimulating protein (F [1.00,7.00]=24.21, p=0.002), tetranectin (F [1.00,7.00]=5.46, p<0.039), vascular endothelial growth factor receptor 3 (F [1.00,7.00]=6.94, p=0.034), and significantly increased for vitronectin (F [1.00,7.00]=5.79, p=0.047). These biomarkers may be of value in detecting cerebral vasospasm, possibly aiding in the identification of patients at high-risk prior to neurological deterioration.
authors.affiliation: Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, White Building Room 502, Boston, MA 02114, USA.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Walcott
authors.affiliation: Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, White Building Room 502, Boston, MA 02114, USA.
authors.forename: Anoop P
authors.initials: AP
authors.lastname: Patel
authors.affiliation: Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, White Building Room 502, Boston, MA 02114, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Stapleton
authors.affiliation: Department of Neurosurgery, Addenbrooke's Hospital and the University of Cambridge, Cambridge, UK.
authors.forename: Rikin A
authors.initials: RA
authors.lastname: Trivedi
authors.affiliation: Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, White Building Room 502, Boston, MA 02114, USA.|Department of Neurosurgery, Addenbrooke's Hospital and the University of Cambridge, Cambridge, UK.
authors.forename: Adam M H
authors.initials: AMH
authors.lastname: Young
authors.affiliation: Department of Neurosurgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Ogilvy
mesh_terms: D000328:Adult; D001054:Apolipoproteins A / Q000097:blood*; D002533:Cerebral Angiography; D005260:Female; D006801:Humans; D008875:Middle Aged; D012259:Ribonuclease, Pancreatic / Q000097:blood*; D013345:Subarachnoid Hemorrhage / Q000097:blood* / Q000150:complications*; D014055:Tomography, Emission-Computed; D020301:Vasospasm, Intracranial / Q000097:blood* / Q000209:etiology*; D000511:alpha-Macroglobulins / Q000378:metabolism*
chemical_list: C578813:A2M protein, human; D001054:Apolipoproteins A; D000511:alpha-Macroglobulins; C022205:apolipoprotein A-IV; C046366:angiogenin; D012259:Ribonuclease, Pancreatic
keywords: Aneurysm; Biomarker; Subarachnoid hemorrhage; Vasospasm
references.citation: J Am Coll Cardiol. 1994 Sep;24(3):636-40
references.pmid: 8077532
references.citation: Neurosurgery. 2006 Jul;59(1):21-7; discussion 21-7
references.pmid: 16823296
references.citation: J Biol Chem. 1997 Jul 4;272(27):17097-103
references.pmid: 9202027
references.citation: Neurotherapeutics. 2012 Jan;9(1):37-43
references.pmid: 22215324
references.citation: Stroke. 1985 Jul-Aug;16(4):562-72
references.pmid: 3895589
references.citation: Nature. 2008 Jul 31;454(7204):656-60
references.pmid: 18594512
references.citation: Stroke. 2002 Feb;33(2):548-52
references.pmid: 11823668
references.citation: Biomarkers. 2014 Mar;19(2):95-108
references.pmid: 24499240
references.citation: Acta Neurol Scand. 2010 Nov;122(5):350-9
references.pmid: 20085559
references.citation: Scand J Immunol. 1993 Jan;37(1):39-42
references.pmid: 8418471
references.citation: Neurology. 2006 Nov 28;67(10):1833-6
references.pmid: 17130418
references.citation: Stroke. 2003 Feb;34(2):427-33
references.pmid: 12574555
references.citation: Curr Opin Lipidol. 2002 Apr;13(2):125-34
references.pmid: 11891414
references.citation: Neurosurgery. 1989 Nov;25(5):736-45; discussion 745-6
references.pmid: 2586727
references.citation: Proc Natl Acad Sci U S A. 1986 Nov;83(22):8457-61
references.pmid: 3095836
references.citation: Neurocrit Care. 2006;4(1):25-31
references.pmid: 16498192
references.citation: Cancer Res. 1999 Oct 15;59(20):5307-14
references.pmid: 10537314
references.citation: Cancer Biother Radiopharm. 2001 Apr;16(2):125-32
references.pmid: 11385959
references.citation: J Neurosurg. 1968 Jan;28(1):14-20
references.pmid: 5635959
references.citation: Crit Rev Immunol. 2013;33(6):549-74
references.pmid: 24266348
references.citation: Acta Neurochir Suppl (Wien). 1988;42:81-4
references.pmid: 3055838
references.citation: J Exp Med. 1991 May 1;173(5):1227-34
references.pmid: 1827141
references.citation: Genes Funct. 1997 Feb;1(1):69-83
references.pmid: 9680329
references.citation: Neurosurgery. 2003 Jul;53(1):123-33; discussion 133-5
references.pmid: 12823881
references.citation: Circulation. 1995 Jun 1;91(11):2844-50
references.pmid: 7758192
references.citation: Eur J Biochem. 1986 Apr 15;156(2):327-33
references.pmid: 3009181
references.citation: Cancer Res. 1992 Apr 15;52(8):2202-8
references.pmid: 1373107
references.citation: Cardiovasc Res. 1994 Dec;28(12):1815-20
references.pmid: 7532547
references.citation: Science. 1985 Jul 5;229(4708):16-22
references.pmid: 2990035
references.citation: Int J Mol Sci. 2010 Sep 02;11(9):3106-21
references.pmid: 20957082
references.citation: Trends Pharmacol Sci. 2001 Jan;22(1):32-9
references.pmid: 11165670
references.citation: Lab Invest. 1991 Jul;65(1):3-14
references.pmid: 1712874
references.citation: J Am Soc Echocardiogr. 2000 Aug;13(8):774-9
references.pmid: 10936822
references.citation: Neurosurgery. 2012 Oct;71(4):869-75
references.pmid: 22801639
references.citation: Science. 1986 Apr 4;232(4746):61-5
references.pmid: 2420009
references.citation: FASEB J. 1992 Dec;6(15):3345-53
references.pmid: 1281457
references.citation: Cancer Lett. 2007 Nov 18;257(2):157-64
references.pmid: 17889431
references.citation: Proc Natl Acad Sci U S A. 1989 Mar;86(5):1573-7
references.pmid: 2646638
references.citation: Eur Neurol. 2007;58(4):224-7
references.pmid: 17823536
references.citation: Life Sci. 2004 Jul 23;75(10):1171-80
references.pmid: 15219805