Stepicheva Nadezda A, Weng Zhongfang, Cao Sarah, Foley Lesley M, Cao Guodong
Department of Neurology, University of Pittsburgh;
Department of Neurology, University of Pittsburgh; Geriatric Research Education and Clinical Center, VA Pittsburgh Healthcare System.
J Vis Exp. 2024 Nov 22(213). doi: 10.3791/67092.
Vascular cognitive impairment and dementia (VCID) results from vascular brain injury. Given VCID's high incidence, which is expected to continue rising as the population ages, it is critical to establish a robust animal model for the disease. This paper presents a novel method of creating a mouse model of VCID that is based on asymmetric bilateral common carotid artery stenosis, which mimics human chronic cerebral hypoperfusion caused by carotid atherosclerosis. Briefly, common carotid arteries (CCAs) are ligated to different gauge needles (32 G for the right CCA and 34 G for the left CCA) using 7-0 silk sutures followed by immediate needle removal. The remaining suture rings cause persistent blood flow reduction and long-term cognitive impairment associated with white matter injury, microinfarcts, and reactive gliosis, thus closely mimicking the pathogenesis of VCID. Importantly, in this needle model, the clinical representations do not revert with time, providing reliable long-term cognitive impairment. Moreover, the survival rate 24 weeks post surgery was 81.6%, which is higher compared to the other established models of VCID with a similar level of blood flow reduction. Additional advantages include low material cost and compatibility with MRI to monitor brain injury in live animals since no metal is implanted. The main challenge in employing the needle model of VCID is the requirement for developing advanced surgical skills since mouse CCAs are less than 0.6 mm in diameter and are very fragile. High-quality visual representation of the surgery will thus help researchers to master this technique and advance our understanding of VCID, potentially leading to the development of novel therapeutic modalities to decrease the devastating cognitive decline associated with VCID.
血管性认知障碍和痴呆（VCID）由脑血管损伤引起。鉴于VCID的高发病率，且随着人口老龄化预计还会持续上升，建立一种可靠的该疾病动物模型至关重要。本文提出了一种基于不对称双侧颈总动脉狭窄创建VCID小鼠模型的新方法，该方法模拟了由颈动脉粥样硬化导致的人类慢性脑灌注不足。简而言之，使用7-0丝线将颈总动脉（CCA）结扎到不同规格的针上（右侧CCA用32G针，左侧CCA用34G针），随后立即拔出针。剩余的缝线环会导致持续的血流减少以及与白质损伤、微梗死和反应性胶质增生相关的长期认知障碍，从而紧密模拟VCID的发病机制。重要的是，在这种针模型中，临床表现不会随时间恢复，可提供可靠的长期认知障碍。此外，术后24周的存活率为81.6%，与其他具有相似血流减少水平的已建立的VCID模型相比更高。其他优点包括材料成本低以及由于未植入金属而与MRI兼容，可用于监测活体动物的脑损伤。采用VCID针模型的主要挑战是需要培养先进的手术技能，因为小鼠CCA的直径小于0.6毫米且非常脆弱。因此，高质量的手术视觉呈现将有助于研究人员掌握这项技术，并增进我们对VCID的理解，有可能导致开发新的治疗方法，以减少与VCID相关的毁灭性认知衰退。
