Department of Neurosurgery, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA.
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.
Transl Stroke Res. 2022 Feb;13(1):188-196. doi: 10.1007/s12975-021-00918-0. Epub 2021 Jun 2.
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.
蛛网膜下腔出血(SAH)与高发病率和死亡率相关,尤其是在动脉瘤破裂后 72 小时内。我们最近在发病后 4 小时的小鼠 SAH 模型中发现了 T2磁共振成像(MRI)可检测到的超早期脑血栓形成。本研究探讨了这种变化是否也会在大鼠中发生,涉及的血管,血栓形成的程度是否随 SAH 严重程度和脑损伤而变化,以及是否存在雄性和雌性大鼠之间的差异。成年 Sprague Dawley 大鼠接受血管内穿孔 SAH 模型或假手术,并在 24 小时后进行 T2 和 T2MRI 检查。SAH 后,MRI 上检测到 T2低信号血管数量增加。这些血管的数量与 MRI 分级评估的出血严重程度相关。组织学上,在苏木精和伊红染色上发现血栓形成的血管,在α-平滑肌肌动蛋白免疫染色上具有单层平滑肌细胞,并且具有层粘连蛋白 2α/纤维蛋白原双重标记,提示 MRI 上 T2-阳性血管是静脉血栓形成的基础。还检测到毛细血管血栓形成,可能紧随静脉血栓形成之后。在雄性和雌性大鼠中,T2*-阳性血栓形成血管的数量与 T2 病变体积和神经功能相关,并且雌性大鼠中这种血管的数量明显更多。总之,本研究在大鼠 SAH 后 24 小时内识别出脑静脉血栓形成,可通过 T2*MRI 成像检测到,可能导致 SAH 引起的脑损伤。