The characteristics of brain injury following cerebral venous infarction induced by surgical interruption of the cortical bridging vein in mice
The characteristics of brain injury following cerebral venous infarction induced by surgical interruption of the cortical bridging vein in mice
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皮质桥静脉手术阻断所致小鼠脑静脉梗死后脑损伤的特点
DOI：
10.1016/j.brainres.2020.146823
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发表时间：
2020-07-15
期刊：
影响因子：
2.9
通讯作者：
Feng, Dayun
中科院分区：
文献类型：
--
作者：
Cai, Qing;Luo, Jianing;Feng, Dayun
由皮质桥静脉（CBV）损伤引起的脑静脉梗死（CVI）是神经外科开颅手术后最严重的并发症之一。与脑动脉梗塞不同，这种CVI病理过程更为复杂，伴有急性静脉高压、脑水肿、脑缺血和桥脑区静脉出血。因此，可靠稳定的小动物模型对于手术CBV中断（CBVi）引起的CVI的病理学研究尤为重要。通过显微外科技术切断从前卤到拉姆达的右侧CBV而建立的小鼠模型用于评估病理过程。成年雄性小鼠在麻醉下横切壁皮肤后进行开颅手术。在手术显微镜下用钻头沿矢状窦右侧边缘去除右侧颅骨（从前囟到拉姆达形成 4 mm x 3 mm 骨窗），暴露右侧 CBV。对脑静脉进行最终检查后，使用双极凝固技术处死 CBV（30% 1 个、60% 2 个、10% 无）。术后不同时间点（6 h、12 h、24 h、48 h）对小鼠进行灌注后颅内压（ICP）监测、运动功能检查、脑水肿评估和脑组织病理学观察。 CBVs解剖后6小时，组织学切片发现大脑半球肿胀、中线移位和皮质下点状出血。 ICP的变化与脑水肿一致，并在术后12小时达到峰值，并且通过伊文思蓝染色评估血脑屏障的破坏。术后半球皮质组织坏死、神经细胞丢失和单核细胞浸润也动态增加。行为测试显示，手术小鼠12 h出现明显的躯体和前肢运动功能障碍，体感严重障碍，48 h基本恢复。我们的研究提供了一种新的手术CBVi引起CVI的小鼠模型，该模型接近临床实践，并初步证实了其病理过程。该模型可能成为研究CVI后神经损伤的临床病理学和分子机制的重要工具。
Cerebral venous infarction (CVI) caused by the injury of cortical bridging veins (CBVs), is one of the most serious complications following neurosurgical craniotomy. Different from cerebral artery infarction, this CVI pathological process is more complicated, accompanied by acute venous hypertension, brain edema, cerebral ischemia and hemorrhage in the veins bridged brain area. Therefore, a reliable and stable small animal model is particularly important for the pathological study of CVI induced by surgical CBV interruption (CBVi). A mouse model established by cutting off the right CBVs from bregma to lambda with microsurgical technique is used for the assessment of the pathological process. Adult male mice underwent craniotomy after transection of the parietal skin under anesthesia. The right CBVs were exposed by removing the right skull along the right lateral edge of the sagittal sinus (forming a 4 mm x 3 mm bone window from bregma to lambda) with a drill under the operating microscope. Following the final inspection of the cerebral veins, the CBVs (30% one, 60% two, 10% none) were sacrificed using bipolar coagulation technique. Intracranial pressure (ICP) monitoring, motor function examination, brain edema assessment and brain histopathological observation after perfusion were performed at different time points (6 h, 12 h, 24 h, and 48 h) in the postoperative mice. Cerebral hemisphere swelling, midline shift and subcortical petechial hemorrhage were found on histological sections 6 h after CBVs dissection. The change of ICP was consistent with cerebral edema and peaked at 12 h after surgery, as well as the disruption of the blood-brain barrier assessed by Evans Blue staining. Tissue necrosis, nerve cell loss and monocytes infiltration were also dynamically increased in the postoperative hemispheric cortex. Behavioral tests showed obvious somato- and forelimb-motor dysfunction, and severe somatosensory disorder on the operative mice at 12 h, which were substantially recovered at 48 h. Our study provided a novel mouse model of CVI caused by surgical CBVi that was close to clinical practice, and preliminarily confirmed its pathological process. This model might become an important tool to study the clinical pathology and the molecular mechanism of nerve injury following CVI.