Mechanisms of microthrombosis and microcirculatory constriction after experimental subarachnoid hemorrhage.

Microcirculatory dysfunction may contribute to delayed cerebral ischemia after subarachnoid hemorrhage (SAH). This study investigated structural changes in microvessels and their relationship to brain injury after SAH. We used 15 mice (n = 5 for each group) to create sham, saline-injected (100 μl 0.9% NaCl) or SAH (100 μl autologous blood) model by injection into the prechiasmatic cistern. We sacrificed mice 2 days after surgery and examined the brains using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and immunohistochemical staining of fibrinogen. We assessed neuronal apoptosis by terminal deoxynucleotidyl transferase dUTP (deoxyuridine triphosphate) nick end labeling (TUNEL). Nitric oxide (NO) was measured with 4,5-diaminofluorescein-2-diacetate. TEM and SEM demonstrated that mice with SAH had significantly more of them arterioles with lesion characteristics consistent with microthrombi. Microthrombi number correlated with the number of apoptotic neurons and decreased NO in the brain. In conclusion, SAH causes microthrombosis and constriction of arterioles, which correlates with neuronal death and decreased NO. These data suggest NO depletion may contribute to the formation of microthrombosis and arteriolar constriction, which in turn results in neuronal cell death.