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.
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.
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