Acute T2*-Weighted Magnetic Resonance Imaging Detectable Cerebral Thrombosis in a Rat Model of Subarachnoid...

Subarachnoid hemorrhage (SAH) is associated with a high incidence of morbidity and mortality, particularly within the first 72 h after aneurysm rupture. We recently found ultra-early cerebral thrombosis, detectable on T2* magnetic resonance imaging (MRI), in a mouse SAH model at 4 h after onset. The current study examined whether such changes also occur in rat at 24 h after SAH, the vessels involved, whether the degree of thrombosis varied with SAH severity and brain injury, and if it differed between male and female rats. Adult Sprague Dawley rats were subjected to an endovascular perforation SAH model or sham surgery and underwent T2 and T2* MRI 24 h later. Following SAH, increased numbers of T2* hypointense vessels were detected on MRI. The number of such vessels correlated with SAH severity, as assessed by MRI-based grading of bleeding. Histologically, thrombotic vessels were found on hematoxylin and eosin staining, had a single layer of smooth muscle cells on alpha-smooth muscle actin immunostaining, and had laminin 2α/fibrinogen double labeling, suggesting venule thrombosis underlies the T2*-positive vessels on MRI. Capillary thrombosis was also detected which may follow the venous thrombosis. In both male and female rats, the number of T2*-positive thrombotic vessels correlated with T2 lesion volume and neurological function, and the number of such vessels was significantly greater in female rats. In summary, this study identified cerebral venous thrombosis 24 h following SAH in rats that could be detected with T2* MRI imaging and may contribute to SAH-induced brain injury.