title: CSF neutrophils are implicated in the development of vasospasm in subarachnoid hemorrhage.
abstract: BACKGROUND
  Cerebral vasospasm is a significant cause of morbidity in patients after aneurysmal subarachnoid hemorrhage (aSAH). There are few effective treatments. The search for new treatments has focused predominantly on dilating cerebral blood vessels. Growing evidence supports a role for inflammation in its pathogenesis but no potential target for intervention has emerged.
  
  
  METHODS
  CSF and clinical information from patients with aSAH were collected. Additionally, tyrosine modifications by stable isotope dilution HPLC with online tandem mass spectrometry were quantified in CSF samples.
  
  
  RESULTS
  We report an association between neutrophil accumulation in the cerebrospinal fluid of patients with aSAH and the development of vasospasm. In particular, CSF neutrophil content of >62% on the third day after aSAH is an independent predictor of the later development of vasospasm (OR 6.8, 95% CI 2.0-23.3, P = 0.002). Further, activity of myeloperoxidase and NADPH oxidase is elevated in aSAH suggesting a role for modification of CSF proteins by reactive oxidant species.
  
  
  CONCLUSIONS
  Neutrophil percentage is an independent predictor of vasospasm in aSAH patients, days prior to its onset suggesting a role of neutrophils in vasospasm. The activity of neutrophil enzymes is also increased suggesting a mechanism for blood vessel damage. Inflammation mediated by neutrophils is a potential target for therapies in vasospasm. More study is necessary to determine the mechanism by which neutrophils damage cerebral blood vessels.
authors.affiliation: NB3, Neuroinflammation Research Center, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, USA. provenj@ccf.org
authors.forename: J J
authors.initials: JJ
authors.lastname: Provencio
authors.forename: X
authors.initials: X
authors.lastname: Fu
authors.forename: A
authors.initials: A
authors.lastname: Siu
authors.forename: P A
authors.initials: PA
authors.lastname: Rasmussen
authors.forename: S L
authors.initials: SL
authors.lastname: Hazen
authors.forename: R M
authors.initials: RM
authors.lastname: Ransohoff
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000134:cerebrospinal fluid; D013345:Subarachnoid Hemorrhage / Q000134:cerebrospinal fluid* / Q000150:complications / Q000503:physiopathology*; D053719:Tandem Mass Spectrometry; D014443:Tyrosine / Q000031:analogs & derivatives / Q000134:cerebrospinal fluid; D020301:Vasospasm, Intracranial / Q000134:cerebrospinal fluid* / Q000150:complications
chemical_list: D017382:Reactive Oxygen Species; C475724:bromotyrosine; D014443:Tyrosine; C087259:3-chlorotyrosine