Depletion of Ly6G/C(+) cells ameliorates delayed cerebral vasospasm in subarachnoid hemorrhage

J Neuroimmunol. 2011 Mar;232(1-2):94-100. doi: 10.1016/j.jneuroim.2010.10.016. Epub 2010 Nov 6.

Abstract

Background: The etiology of delayed cerebral vasospasm (DCV) after aneurysmal subarachnoid hemorrhage (SAH) has remained elusive. Growing evidence supports a role for inflammation in the pathogenesis of DCV. We showed that CSF neutrophils predict which patients will develop DCV.

Methods: We evaluated a murine model of SAH to test the hypothesis that myeloid cells are required for the cerebral damage associated with DCV.

Results: SAH was associated with decreased middle cerebral artery caliber on day 1 which normalized at day 3 and recurred at day 6. In addition, behavioral testing with a Barnes maze showed executive dysfunction that progressively worsened after the seventh day post hemorrhage. To test the role of innate immune responses, we administrated a myeloid cell-depleting monoclonal antibody against Ly6G/C prior to experimental SAH. Myeloid cell depletion ameliorated angiographic vasospasm measured by MCA vessel caliber and normalized behavioral testing.

Conclusion: Our findings support the role of Ly6G/C(+) cells in the development of DCV after SAH and suggest that immune modulation of neutrophils or other Ly6G/C(+) cells may be a strategy for the prevention of DCV.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, Ly / immunology
  • Antigens, Ly / metabolism
  • Cell Separation
  • Disease Models, Animal
  • Flow Cytometry
  • Immunohistochemistry
  • Inflammation / complications*
  • Inflammation / immunology*
  • Male
  • Maze Learning
  • Mice
  • Mice, Inbred C57BL
  • Middle Cerebral Artery / immunology
  • Middle Cerebral Artery / pathology
  • Myeloid Cells / immunology
  • Myeloid Cells / metabolism
  • Neutrophils / immunology*
  • Neutrophils / metabolism
  • Subarachnoid Hemorrhage / complications*
  • Subarachnoid Hemorrhage / immunology*
  • Subarachnoid Hemorrhage / pathology
  • Vasospasm, Intracranial / immunology*
  • Vasospasm, Intracranial / pathology

Substances

  • Antigens, Ly
  • Ly-6C antigen, mouse
  • Ly6G antigen, mouse