title: Systemic administration of LPS worsens delayed deterioration associated with vasospasm after subarachnoid hemorrhage through a myeloid cell-dependent mechanism.
abstract: BACKGROUND
  Delayed deterioration associated with vasospasm (DDAV) after aneurismal subarachnoid hemorrhage (SAH) is a major cause of morbidity. We have previously shown that myeloid cell depletion before experimental SAH in a murine model ameliorates DDAV. In this study, we address whether systemic administration of lipopolysaccharide (LPS) worsens DDAV in a myeloid cell-dependent fashion.
  
  
  METHODS
  We challenged mice in our experimental SAH model with LPS before hemorrhage and evaluated the degree of vasospasm on day 6 with India ink angiography; behavioral deficits by rotorod, Y-maze, and Barnes maze testing; microglial activation early after SAH by immunohistochemistry; and the brain levels of the chemokines CCL5 and KC at the time of vasospasm. Another group of animals were given the myeloid cell-depleting antibody against the neutrophil antigen Ly6G/C prior to LPS administration and SAH.
  
  
  RESULTS
  LPS followed by SAH significantly worsens angiographic vasospasm as well as performance on the Barnes maze but not the Y-maze or rotorod tests. There was an increased activation of microglia in animals with LPS before SAH compared to SAH alone. Depletion of myeloid cells before LPS administration inhibited the development of vasospasm, improved the performance on behavioral tests, and reduced microglial activation. The chemokines CCL5 and KC were incrementally elevated in SAH and LPS SAH, but suppressed in animals with myeloid cell depletion.
  
  
  CONCLUSIONS
  LPS administration before SAH worsens DDAV through a myeloid cell-dependent mechanism supporting studies in humans which show that systemic inflammation increases the likelihood of developing DDAV.
authors.affiliation: Cerebrovascular Center, Cleveland Clinic, NC30, 9500 Euclid Ave., Cleveland, OH 44195, USA.
authors.forename: Saksith
authors.initials: S
authors.lastname: Smithason
authors.forename: Shari Korday
authors.initials: SK
authors.lastname: Moore
authors.forename: J Javier
authors.initials: JJ
authors.lastname: Provencio
mesh_terms: D000818:Animals; D018925:Chemokines / Q000276:immunology; D007113:Immunity, Innate; D007249:Inflammation / Q000150:complications / Q000276:immunology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D023421:Models, Animal; D022423:Myeloid Cells / Q000276:immunology*; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000276:immunology*; D020301:Vasospasm, Intracranial / Q000209:etiology / Q000276:immunology*
chemical_list: D018925:Chemokines; D008070:Lipopolysaccharides
references.citation: J Neurosurg. 2003 Aug;99(2):376-82
references.pmid: 12924713
references.citation: Stroke. 2011 Apr;42(4):924-9
references.pmid: 21311062
references.citation: J Neuroimmunol. 2011 Mar;232(1-2):94-100
references.pmid: 21059474
references.citation: Australas Radiol. 1993 May;37(2):156-60
references.pmid: 8512504
references.citation: Brain Res. 2004 Nov 5;1026(1):23-32
references.pmid: 15476694
references.citation: J Cereb Blood Flow Metab. 2005 Aug;25(8):1070-7
references.pmid: 15789034
references.citation: Neurosurg Focus. 2006 Sep 15;21(3):E2
references.pmid: 17029341
references.citation: Neurosurgery. 2008 Dec;63(6):1095-104; discussion 1004-5
references.pmid: 19057321
references.citation: Neurocrit Care. 2008;8(3):404-12
references.pmid: 18196475
references.citation: J Neurosurg. 2002 Sep;97(3):676-82
references.pmid: 12296653
references.citation: Surg Neurol. 2006 Nov;66(5):463-9; discussion 469
references.pmid: 17084186
references.citation: J Neurosci Methods. 2009 Oct 15;183(2):136-40
references.pmid: 19576247
references.citation: Semin Neurol. 2005 Dec;25(4):435-44
references.pmid: 16341999
references.citation: Brain. 2001 Feb;124(Pt 2):249-78
references.pmid: 11157554
references.citation: Surg Neurol. 2000 Sep;54(3):221-7; discussion 227-8
references.pmid: 11118568
references.citation: J Neurol Neurosurg Psychiatry. 2004 Aug;75(8):1119-24
references.pmid: 15258212
references.citation: J Cereb Blood Flow Metab. 2011 Jun;31(6):1443-51
references.pmid: 21285966
references.citation: J Leukoc Biol. 2002 Aug;72(2):373-81
references.pmid: 12149429
references.citation: Stroke. 2007 Dec;38(12):3266-71
references.pmid: 17962599
references.citation: Neurocrit Care. 2010 Oct;13(2):182-9
references.pmid: 20593247
references.citation: J Neurosurg. 2004 Jul;101(1):88-92
references.pmid: 15255256
references.citation: J Cereb Blood Flow Metab. 2004 Apr;24(4):419-31
references.pmid: 15087711
references.citation: Stroke. 2001 Sep;32(9):1989-93
references.pmid: 11546886
references.citation: Neurocrit Care. 2010 Apr;12(2):244-51
references.pmid: 19967568
references.citation: Stroke. 2001 Jan;32(1):212-7
references.pmid: 11136939