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


CONCLUSIONS
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.
Neuroinflammation Research Center, Lerner Research Institute, NB3, Cleveland Clinic, 9500 Euclid Ave. Cleveland, OH 44195, United States. provenj@ccf.org
J Javier
JJ
Provencio
Tamer
T
Altay
Saksith
S
Smithason
Shari Korday
SK
Moore
Richard M
RM
Ransohoff
D000818:Animals; D000950:Antigens, Ly / Q000276:immunology / Q000378:metabolism; D002469:Cell Separation; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007249:Inflammation / Q000150:complications* / Q000276:immunology*; D008297:Male; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D020768:Middle Cerebral Artery / Q000276:immunology / Q000473:pathology; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000276:immunology* / Q000473:pathology; D020301:Vasospasm, Intracranial / Q000276:immunology* / Q000473:pathology
D000950:Antigens, Ly; C494192:Ly-6C antigen, mouse; C480309:Ly6G antigen, mouse