Neurocritical Care

, Volume 12, Issue 2, pp 244–251 | Cite as

CSF Neutrophils Are Implicated in the Development of Vasospasm in Subarachnoid Hemorrhage

  • J. J. Provencio
  • X. Fu
  • A. Siu
  • P. A. Rasmussen
  • S. L. Hazen
  • R. M. Ransohoff
Original Article



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.


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.


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.


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.


Subarachnoid hemorrhage Cerebral vasospasm Neutrophil Inflammation Reactive oxidant species 



Hypochlorous acid


Hypobromous acid


Liquid chromatography electrospray, ionization tandem mass spectrometry


Eosinophil peroxidase





The authors would like to thank Michael Chow, MD, MPH, University of Alberta for his help with the 2000–2002 database; Rishi Gupta, MD for statistical help and review of the manuscript; and Edward Manno, MD and Saksith Smithason, MD for review of the manuscript. This work was supported by National Institutes of Health Grants K08 NS051350 (to J.J.P), and P01 HL076491 (to S.L.H.), and K24 NS51400 (to R.M.R).


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • J. J. Provencio
    • 1
    • 4
  • X. Fu
    • 2
  • A. Siu
    • 1
  • P. A. Rasmussen
    • 4
  • S. L. Hazen
    • 2
    • 3
  • R. M. Ransohoff
    • 1
  1. 1.NB3, Neuroinflammation Research Center, Lerner Research InstituteCleveland ClinicClevelandUSA
  2. 2.Department of Cell Biology, Lerner Research InstituteCleveland ClinicClevelandUSA
  3. 3.Cardiovascular Medicine and Center for Cardiovascular Diagnostics & PreventionCleveland ClinicClevelandUSA
  4. 4.Cerebrovascular CenterCleveland ClinicClevelandUSA

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