Mechanisms of microthrombi formation after experimental subarachnoid hemorrhage.
Microcirculatory dysfunction may contribute to delayed cerebral ischemia after subarachnoid hemorrhage (SAH). Using a prechiasmatic injection model, this study investigated ultrastructural changes in microvessels in brain parenchyma to determine the nature of the microthromboemboli, the involvement of nitric oxide (NO) and P-selectin in their formation, and relationship to brain injury after SAH. Brains were examined by electron microscopy (EM) and immunohistochemistry. EM demonstrated that mice with SAH had significantly more arterioles filled with lesions consistent with microthrombi (in cortex, 20 ± 5 for SAH, 8 ± 4 saline-injected and 2.4 ± 0.2 for sham). SAH animals also had more constriction of arterioles. The concentration of NO was lower in mice with SAH (44 ± 9 for sham, 46 ± 20 for saline-injected and 24 ± 11 for SAH). The number of microthrombi correlated with the number of apoptotic neuronal cells (R(2)=0.80 in cortex). Cell membrane P-selectin increased in the endothelium of arterioles in mice with SAH (11.4 ± 0.7 for SAH, 6.8 ± 0.9 for sham and 6.1 ± 0.9 for saline-injected controls). This correlated with decreased NO in the brain. In conclusion, SAH causes microthrombosis and constriction of arterioles, which correlates with neuronal cell death. Increased P-selectin and decreased NO suggest a mechanism for microthrombosis and arteriolar constriction.
Institute of Medical Science, University of Toronto, Ontario, Canada.
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M
Sabri
J
J
Ai
K
K
Lakovic
J
J
D'abbondanza
D
D
Ilodigwe
R L
RL
Macdonald
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001160:Arterioles / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D020767:Intracranial Thrombosis / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D009474:Neurons / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D013345:Subarachnoid Hemorrhage / Q000378:metabolism* / Q000473:pathology*; D014661:Vasoconstriction / Q000502:physiology
D019007:P-Selectin; D009569:Nitric Oxide