Wroe William, Dienel Ari, Hong Sungha, Matsumura Kanako, Guzman Jose, Torres Kiara, Bernal Angelica, Zeineddine Hussein A, Pandit Peeyush Thankamani, Blackburn Spiros L, McBride Devin W
The Vivian L. Smith Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
Cornell University, Ithaca, New York.
Brain Hemorrhages. 2024 Jun;5(3):99-106. doi: 10.1016/j.hest.2023.12.006. Epub 2023 Dec 30.
Delayed cerebral ischemia (DCI) is one of the most feared complications in aneurysmal subarachnoid hemorrhage (SAH). Animal models are crucial to studying the disease mechanisms and potential treatments. DCI in rodents was thought to not exist; herein we examine literature and our experience with DCI in rodents.
Daily behavioral performance was assessed every day from day 1 to up to 7 days post-SAH on mice from 5 different studies that used the endovascular perforation model. Performance was graded using an 8-test sensorimotor neuroscore previously described. The daily neuroscore was then used to identify the incidence and timing of delayed neurological deficits, a clinical surrogate for DCI. A total number of 298 mice (134 males, 164 females) were subjected to SAH. Fifty-one mice had histological staining done to identify infarct volume.
The overall incidence of DND was 33.9%; 27.6% in males and 39.0% in females, but this difference was not statistically significant. The overall incidence of delayed death was 21.1%, and there was no significant difference for delayed mortality in females versus male mice. There is a non-statistically significant trend towards increased infarct volume in mice suffering DND.
Mice with endovascular puncture induced SAH develop DND at rates comparable to human patients. Future work needs to correlate the DND seen with decreased regional cerebral blood flow, another hallmark of DCI, but in spite of this need, researchers may use the murine models to test therapies for DCI after SAH.
迟发性脑缺血（DCI）是动脉瘤性蛛网膜下腔出血（SAH）最可怕的并发症之一。动物模型对于研究疾病机制和潜在治疗方法至关重要。以往认为啮齿动物不存在DCI；在此我们研究相关文献并分享我们在啮齿动物DCI方面的经验。
对来自5项使用血管内穿刺模型的不同研究中的小鼠，在SAH后第1天至第7天每天评估其日常行为表现。使用先前描述的8项测试感觉运动神经评分对表现进行分级。然后使用每日神经评分来确定延迟性神经功能缺损的发生率和时间，延迟性神经功能缺损是DCI的临床替代指标。共有298只小鼠（134只雄性，164只雌性）接受了SAH。51只小鼠进行了组织学染色以确定梗死体积。
延迟性神经功能缺损的总体发生率为33.9%；雄性为27.6%，雌性为39.0%，但这种差异无统计学意义。延迟死亡的总体发生率为21.1%，雌性和雄性小鼠的延迟死亡率无显著差异。发生延迟性神经功能缺损的小鼠梗死体积有增加的趋势，但无统计学意义。
血管内穿刺诱导SAH的小鼠发生延迟性神经功能缺损的比率与人类患者相当。未来的工作需要将观察到的延迟性神经功能缺损与局部脑血流量减少相关联，局部脑血流量减少是DCI的另一个特征，尽管有此需求，但研究人员可使用小鼠模型来测试SAH后DCI的治疗方法。
