Department of Neurosurgery, University of Michigan, Ann Arbor (Z.W., J.C., Y.T., R.F.K., G.X., Y.H.).
Department of Neurosurgery, The First Hospital of Ningbo, Zhejiang, China (Z.W.).
Stroke. 2021 Mar;52(3):1033-1042. doi: 10.1161/STROKEAHA.120.032397. Epub 2021 Feb 4.
The mechanisms of brain damage during ultra-early subarachnoid hemorrhage (SAH) have not been well studied. The current study examined the SAH-induced hyperacute brain damage at 4 hours using magnetic resonance imaging and brain histology in a mouse model.
SAH was induced by endovascular perforation in adult mice. First, adult male wild-type mice underwent magnetic resonance imaging T2 and T2* 4 hours after an endovascular perforation or a sham operation and were euthanized to assess brain histology. Second, male and female adult lipocalin-2 knockout mice had SAH. All animals underwent magnetic resonance imaging at 4 hours, and the brains were harvested for brain histology.
T2* hypointensity vessels were observed in the brain 4 hours after SAH in male wild-type mice. The numbers of T2*-positive vessels were significantly higher in SAH brains than in sham-operated mice. Brain histology showed thrombosis and erythrocyte plugs in the T2*-positive cerebral vessels which may be venules. The number of T2*-positive vessels correlated with SAH grade and the presence of T2 lesions. Brain thrombosis was also accompanied by albumin leakage and neuronal injury. LCN2 deficient male mice had lower numbers of T2*-positive vessels after SAH compared with wild-type male mice.
SAH causes ultra-early brain vessel thrombosis that can be detected by T2* gradient-echo sequence at 4 hours after SAH. LCN2 deficiency decreased the number of T2*-positive vessels.
超早期蛛网膜下腔出血（SAH）期间的脑损伤机制尚未得到充分研究。本研究通过磁共振成像和脑组织学检查，在小鼠模型中观察了 4 小时内 SAH 引起的超急性脑损伤。
通过血管内穿孔在成年小鼠中诱导 SAH。首先，成年雄性野生型小鼠在血管内穿孔或假手术后 4 小时进行磁共振成像 T2 和 T2*，并进行安乐死以评估脑组织学。其次，雄性和雌性成年载脂蛋白 L2 敲除小鼠发生 SAH。所有动物在 4 小时时进行磁共振成像，然后取出大脑进行脑组织学检查。
SAH 后 4 小时，雄性野生型小鼠的大脑中观察到 T2低信号血管。SAH 脑内 T2-阳性血管数量明显高于假手术组。脑组织学显示 T2*-阳性脑血管内有血栓和红细胞栓子，可能是小静脉。T2*-阳性血管的数量与 SAH 分级和 T2 病变的存在相关。脑血栓形成还伴有白蛋白渗漏和神经元损伤。与野生型雄性小鼠相比，LCN2 缺乏的雄性小鼠在 SAH 后 T2*-阳性血管的数量减少。
SAH 导致超早期脑血管血栓形成，可在 SAH 后 4 小时通过 T2梯度回波序列检测到。LCN2 缺乏减少了 T2-阳性血管的数量。
