Vascular dementia (VaD) is one of the most common types of dementia followed by Alzheimer's disease (AD). Recent studies showed that approximately 30 %–35 % of patients with AD at post-mortem exhibited vascular pathologies, which suggested that mixed dementia may be the most common type of dementia. Permanent bilateral common carotid artery occlusion (2VO) is a well-characterized method for investigating cognitive functions and the histopathological consequences of chronic cerebral hypoperfusion (CCH) in rats. In the present study, we investigated the effects of environmental enrichment (EE) on cognitive impairment after CCH, as well as the effects of CCH-induced neurovascular damage on cognitive function. Wistar rats were randomly allocated to a sham group, a 2VO group, and a 2VO + EE group. The 2VO procedure was performed at 12 weeks, while EE was performed for 8 weeks before and 6 weeks after 2VO. The effect of EE on cognitive functions in 2VO rats was investigated using the radial-arm maze and Morris Water Maze tests. Neurovascular integrity was assessed based on immunoreactivity for glial fibrillary acidic protein (GFAP), morphological changes in microvessels, and the expression of matrix metalloproteinase-9 (MMP-9) and zonula occludens-1 (ZO-1) in the motor cortex and hippocampus. EE ameliorated microvessel fragmentation by sustaining the tight junction through increases of ZO-1 expression after CCH, resulting in preserving the neurovascular unit. In summary, EE mitigated cognitive impairment by restoring neurovascular integrity. These findings suggest that EE can be a valuable and meaningful environmental intervention for patients with cognitive impairment.

血管性痴呆 (VaD) 是最常见的痴呆类型之一，其次是阿尔茨海默病 (AD)。最近的研究表明，大约 30%–35% 的 AD 患者死后会出现血管病变，这表明混合性痴呆可能是最常见的痴呆类型。永久性双侧颈总动脉闭塞 (2VO) 是研究大鼠慢性脑灌注不足 (CCH) 的认知功能和组织病理学后果的一种公认方法。在本研究中，我们研究了环境富集 (EE) 对 CCH 后认知障碍的影响，以及 CCH 诱导的神经血管损伤对认知功能的影响。Wistar 大鼠随机分为假手术组、2VO 组和 2VO + EE 组。2VO 程序在第 12 周进行，EE 在 2VO 前 8 周和 2VO 后 6 周进行。使用径向臂迷宫和莫里斯水迷宫试验研究 EE 对 2VO 大鼠认知功能的影响。根据神经胶质纤维酸性蛋白 (GFAP) 的免疫反应性、微血管的形态变化以及运动皮层和海马中基质金属蛋白酶-9 (MMP-9) 和闭塞小带-1 (ZO-1) 的表达来评估神经血管完整性. EE 通过在 CCH 后通过增加 ZO-1 表达维持紧密连接来改善微血管破碎，从而保护神经血管单元。总之，EE 通过恢复神经血管完整性来减轻认知障碍。这些发现表明，对于认知障碍患者，EE 可能是一种有价值且有意义的环境干预措施。