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

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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.

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Abbreviations

HOCl:

Hypochlorous acid

HOBr:

Hypobromous acid

LC/ESI/MS/MS:

Liquid chromatography electrospray, ionization tandem mass spectrometry

EPO:

Eosinophil peroxidase

MPO:

Myeloperoxidase

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Acknowledgments

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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Authors and Affiliations

  1. NB3, Neuroinflammation Research Center, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH, 44195, USA

    J. J. Provencio, A. Siu & R. M. Ransohoff

  2. Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH, 44195, USA

    X. Fu & S. L. Hazen

  3. Cardiovascular Medicine and Center for Cardiovascular Diagnostics & Prevention, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH, 44195, USA

    S. L. Hazen

  4. Cerebrovascular Center, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH, 44195, USA

    J. J. Provencio & P. A. Rasmussen

Authors
  1. J. J. Provencio
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  2. X. Fu
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  3. A. Siu
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  4. P. A. Rasmussen
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  5. S. L. Hazen
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  6. R. M. Ransohoff
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Correspondence to J. J. Provencio.

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Provencio, J.J., Fu, X., Siu, A. et al. CSF Neutrophils Are Implicated in the Development of Vasospasm in Subarachnoid Hemorrhage. Neurocrit Care 12, 244–251 (2010). https://doi.org/10.1007/s12028-009-9308-7

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  • DOI: https://doi.org/10.1007/s12028-009-9308-7

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