Neurovascular Research Group, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.
Department of Stroke and Cerebrovascular Diseases, National Cerebral and Cardiovascular Centre, Osaka, Japan.
Neuropathol Appl Neurobiol. 2019 Dec;45(7):681-697. doi: 10.1111/nan.12550. Epub 2019 May 23.
Carotid artery disease (CAD) is an important risk factor for stroke. We first evaluated CAD and stroke pathology in elderly post-stroke survivors. To simulate CAD, we assessed long-term consequences of bilateral common carotid artery stenosis (BCAS) in mice and exposed them to environmental enrichment (EE).
Histopathological methods were used to determine degrees of CAD (% area stenosis), brain infarct types, sizes and distribution in post-stroke survivors and BCAS mice. Adult male C57BL/6J mice after BCAS or sham surgery were randomly assigned to standard housing (Std) or limited (3 h) or full-time (Full) exposure to EE per day for 12 weeks.
High frequencies of moderate carotid artery stenosis (51-75%) were evident in post-stroke survivors whereas those with severe CAD (>75% stenosis) exhibited greater numbers of cortical rather than subcortical infarcts and, were at higher risk of developing dementia. BCAS in mice reduced cerebral blood flow by 52% (P < 0.01) and thickened carotid artery walls, regardless of EE duration. Remarkably, the total and cortical infarcts declined by >50% in BCAS mice exposed to EE compared with BCAS-Std (P < 0.01). Frontal lobe and cortical strokes were associated with worsening working memory tested in a radial maze paradigm. Proteomic analysis revealed EE, both BCAS-3 h and BCAS-Full attenuated coagulation cascade factors including fibrinogen and von Willebrand factor, markers of blood-brain barrier damage.
Small cortical and subcortical infarcts were evident in both post-stroke survivors with CAD and BCAS mice. Experimental evidence suggested that moderate exposure to EE is sufficient to reduce subsequent stroke lesions.
颈动脉疾病（CAD）是中风的一个重要危险因素。我们首先评估了老年中风幸存者的 CAD 和中风病理学。为了模拟 CAD，我们评估了双侧颈总动脉狭窄（BCAS）对小鼠的长期影响，并使其暴露于环境丰富（EE）中。
采用组织病理学方法确定 CAD 的程度（狭窄面积百分比）、中风幸存者和 BCAS 小鼠的脑梗死类型、大小和分布。BCAS 或假手术后的成年雄性 C57BL/6J 小鼠被随机分配到标准饲养（Std）或每天限时（3 小时）或全时（Full）暴露于 EE 中 12 周。
中风幸存者中出现了较高频率的中度颈动脉狭窄（51-75%），而严重 CAD（>75%狭窄）患者则表现出更多的皮质而非皮质下梗死，并且发生痴呆的风险更高。无论 EE 持续时间如何，BCAS 都会使小鼠的脑血流减少 52%（P<0.01）并使颈动脉壁变厚。值得注意的是，与 BCAS-Std 相比，暴露于 EE 的 BCAS 小鼠的总梗死和皮质梗死减少了>50%（P<0.01）。EE 以及 BCAS-3 小时和 BCAS-全时暴露均可降低放射状迷宫测试中的工作记忆，而额叶和皮质中风则与工作记忆恶化有关。蛋白质组学分析表明，EE、BCAS-3 小时和 BCAS-全时均可减轻凝血级联因子，包括纤维蛋白原和血管性血友病因子，这是血脑屏障损伤的标志物。
CAD 患者和 BCAS 小鼠均出现小的皮质和皮质下梗死。实验证据表明，适度暴露于 EE 足以减少随后的中风损伤。
