Department of Nursing, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea.
College of Nursing Science, Kyung Hee University, East-west Nursing Research Institute, Seoul, 02447, Republic of Korea.
Brain Res Bull. 2020 Oct;163:160-169. doi: 10.1016/j.brainresbull.2020.07.020. Epub 2020 Jul 22.
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）是继阿尔茨海默病（AD）之后最常见的痴呆症类型之一。最近的研究表明，大约 30%-35%的 AD 患者在死后表现出血管病变，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）是一种研究认知功能和慢性脑灌注不足（CCH）大鼠组织病理学后果的成熟方法。在本研究中，我们研究了环境丰富（EE）对 CCH 后认知障碍的影响，以及 CCH 引起的神经血管损伤对认知功能的影响。Wistar 大鼠被随机分配到假手术组、2VO 组和 2VO+EE 组。2VO 手术在 12 周进行，而 EE 在 2VO 之前进行 8 周，在 2VO 之后进行 6 周。使用放射臂迷宫和 Morris 水迷宫测试研究 EE 对 2VO 大鼠认知功能的影响。根据胶质纤维酸性蛋白（GFAP）的免疫反应性、微血管形态变化以及运动皮层和海马中基质金属蛋白酶-9（MMP-9）和封闭蛋白-1（ZO-1）的表达来评估神经血管完整性。EE 通过增加 CCH 后 ZO-1 的表达来维持紧密连接，从而改善微血管碎裂，从而维持神经血管单元。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，EE 可以为认知障碍患者提供一种有价值和有意义的环境干预措施。
