title: Cerebrospinal fluid 20-HETE is associated with delayed cerebral ischemia and poor outcomes after aneurysmal subarachnoid hemorrhage.
abstract: OBJECTIVE
  Delayed cerebral ischemia (DCI) is a major complication after aneurysmal subarachnoid hemorrhage (aSAH); it is manifested by changes in cerebral blood flow accompanied by neurological decline, and it results in long-term functional and neuropsychological impairment. Preclinical evidence has demonstrated that the arachidonic acid metabolite, 20-hydroxyeicosatetraenoic acid (20-HETE), affects cerebral microvascular tone and cerebral blood flow after aSAH. The purpose of this study was to determine whether cerebrospinal fluid 20-HETE levels were associated with DCI and long-term neuropsychological outcomes in aSAH patients.
  
  
  METHODS
  Cerebrospinal fluid samples were collected twice daily through 14 days after hemorrhage on 108 acute, adult, aSAH patients. Samples were analyzed for 20-HETE via HPLC MSQ single quadrupole mass spectrometry. DCI was defined as the presence of impaired cerebral blood flow (angiographic vasospasm, elevated transcranial Dopplers, abnormal computed tomography or magnetic resonance perfusion scans) accompanied by neurological deterioration. Outcomes, including death and neuropsychological testing, were completed at 3 months after hemorrhage.
  
  
  RESULTS
  Detectable 20-HETE levels were observed in 31% of patient samples and were associated with severity of hemorrhage (Hunt & Hess [HH], P=0.04; Fisher, P=0.05). Detection of 20-HETE was not associated with angiographic vasospasm (P=0.34); however, detectable 20-HETE was significantly associated with DCI (P=0.016). Our data also suggest that detectable 20-HETE was associated with decreased performance in 5 neuropsychological domains.
  
  
  CONCLUSIONS
  These results provide the first clinical evidence that cerebrospinal fluid 20-HETE concentrations are associated with DCI and poor outcomes, and this provides impetus for future studies to elucidate the clinical utility of inhibiting 20-HETE formation as a novel therapeutic intervention in patients with aSAH.
authors: School of Pharmacy, University of Pittsburgh, 807 Salk Hall, Pittsburgh, PA 15261, USA.
authors: Elizabeth A
authors: EA
authors: Crago
authors: Bhavani P
authors: BP
authors: Thampatty
authors: Paula R
authors: PR
authors: Sherwood
authors: Chie-Wen J
authors: CW
authors: Kuo
authors: Catherine
authors: C
authors: Bender
authors: Jeffrey
authors: J
authors: Balzer
authors: Michael
authors: M
authors: Horowitz
authors: Samuel M
authors: SM
authors: Poloyac
references: Stroke. 2010 Oct;41(10):2391-5
references: 20798370
references: J Neurosci Methods. 2005 Jun 15;144(2):257-63
references: 15910986
references: Am J Physiol Heart Circ Physiol. 2005 Nov;289(5):H2203-11
references: 15964920
references: Circulation. 2005 Jan 4;111(1):63-9
references: 15611369
references: Am J Physiol Heart Circ Physiol. 2002 Apr;282(4):H1556-65
references: 11893593
references: Behav Modif. 2008 Jan;32(1):3-20
references: 18096969
references: Neurol Res. 2009 Jul;31(6):626-31
references: 19055879
references: Hypertension. 2008 Aug;52(2):373-80
references: 18574070
references: Stroke. 2008 Nov;39(11):3015-21
references: 18688013
references: Eur J Pharmacol. 2004 Feb 23;486(3):297-306
references: 14985052
references: Am J Physiol Regul Integr Comp Physiol. 2006 Jan;290(1):R84-9
references: 16166205
references: Am J Physiol Heart Circ Physiol. 2006 Nov;291(5):H2301-7
references: 16782846
references: Am J Physiol. 1994 May;266(5 Pt 2):H2098-107
references: 8203608
references: J Neurosci Res. 2009 Jan;87(1):1-11
references: 18709660
references: J Cereb Blood Flow Metab. 2008 Nov;28(11):1761-70
references: 18628782
references: Neuroradiology. 2009 Feb;51(2):85-93
references: 18850093
references: Clin Neuropsychol. 2004 Aug;18(3):373-84
references: 15739809
references: Stroke. 2009 Jun;40(6):1963-8
references: 19359629
references: AJNR Am J Neuroradiol. 2006 Jun-Jul;27(6):1350-4
references: 16775295
references: J Neurosurg. 2011 Apr;114(4):961-8
references: 20849218
references: Am J Physiol Heart Circ Physiol. 2003 May;284(5):H1528-35
references: 12521947
references: J Cereb Blood Flow Metab. 2009 Mar;29(3):629-39
references: 19107134
references: Front Biosci. 2008 Jan 01;13:1845-56
references: 17981672
references: J Int Neuropsychol Soc. 2001 Jul;7(5):597-605
references: 11459111
references: Hypertension. 2008 May;51(5):1393-8
references: 18391101
references: Hypertension. 2008 Mar;51(3):767-72
references: 18227405
references: J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Sep 5;794(2):363-72
references: 12954388
references: Stroke. 2006 May;37(5):1307-13
references: 16601220
references: World Neurosurg. 2010 Jun;73(6):654-67
references: 20934153
references: Physiol Rev. 2002 Jan;82(1):131-85
references: 11773611
references: Behav Brain Sci. 2006 Apr;29(2):109-25; discussion 125-60
references: 16606477
references: Glia. 2007 Sep;55(12):1214-21
references: 17659528
references: Stroke. 2009 Feb;40(2):e39; author reply e40
references: 19074477
references: J Cereb Blood Flow Metab. 2006 Dec;26(12):1551-61
references: 16570075
references: Appl Neuropsychol. 1995 May;2(2):79-88
references: 16318528
references: Neurol Res. 2006 Oct;28(7):738-49
references: 17164037
references: Neuroradiology. 2009 Dec;51(12):813-9
references: 19623472
references: Stroke. 2010 Oct;41(10 Suppl):S79-84
references: 20876512