BACKGROUND Brain circulation disorders such as chronic cerebral hypoperfusion have been associated with a decline in cognitive function during the development of dementia. Astrocytes together with microglia participate in the immune response in the CNS and make them potential sentinels in the brain parenchyma. In addition, astrocytes coverage integrity has been related to brain homeostasis. Currently, physical exercise has been proposed as an effective intervention to promote brain function improvement. However, the neuroprotective effects of early physical exercise on the astrocyte communication with the microcirculation and the microglial activation in a chronic cerebral hypoperfusion model are still unclear. The aim of this study was to investigate the impact of early intervention with physical exercise on cognition, brain microcirculatory, and inflammatory parameters in an experimental model of chronic cerebral hypoperfusion induced by permanent bilateral occlusion of the common carotid arteries (2VO). METHODS Wistar rats aged 12 weeks were randomly divided into four groups: Sham-sedentary group (Sham-Sed), Sham-exercised group (Sham-Ex), 2VO-sedentary group (2VO-Sed), and 2VO-exercised group (2VO-Ex). The early intervention with physical exercise started 3 days after 2VO or Sham surgery during 12 weeks. Then, the brain functional capillary density and endothelial-leukocyte interactions were evaluated by intravital microscopy; cognitive function was evaluated by open-field test; hippocampus postsynaptic density protein 95 and synaptophysin were evaluated by western blotting; astrocytic coverage of the capillaries, microglial activation, and structural capillary density were evaluated by immunohistochemistry. RESULTS Early moderate physical exercise was able to normalize functional capillary density and reduce leukocyte rolling in the brain of animals with chronic cerebral hypoperfusion. These effects were accompanied by restore synaptic protein and the improvement of cognitive function. In addition, early moderate exercise improves astrocytes coverage in blood vessels of the cerebral cortex and hippocampus, decreases microglial activation in the hippocampus, and improves structural capillaries in the hippocampus. CONCLUSIONS Microcirculatory and inflammatory changes in the brain appear to be involved in triggering a cognitive decline in animals with chronic cerebral ischemia. Therefore, early intervention with physical exercise may represent a preventive approach to neurodegeneration caused by chronic cerebral hypoperfusion.

中文翻译：

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在慢性脑灌注不足模型中，体育锻炼可促进星形胶质细胞对微血管的覆盖。


背景技术脑循环障碍例如慢性脑灌注不足与痴呆发展期间认知功能下降相关。星形胶质细胞与小胶质细胞一起参与中枢神经系统的免疫反应，并使它们成为脑实质中潜在的哨兵。此外，星形胶质细胞覆盖完整性与大脑稳态有关。目前，体育锻炼已被提出作为促进大脑功能改善的有效干预措施。然而，早期体育锻炼对慢性脑低灌注模型中星形胶质细胞与微循环的通讯以及小胶质细胞激活的神经保护作用仍不清楚。本研究的目的是在双侧颈总动脉永久性闭塞（2VO）引起的慢性脑灌注不足的实验模型中，探讨早期体育锻炼干预对认知、脑微循环和炎症参数的影响。方法 12周龄Wistar大鼠随机分为4组：假静坐组（Sham-Sed）、假运动组（Sham-Ex）、2VO静坐组（2VO-Sed）、2VO运动组（2VO -前任）。在 12 周的 2VO 或假手术后 3 天开始进行早期体育锻炼干预。然后，通过活体显微镜评估脑功能毛细血管密度和内皮-白细胞相互作用；通过旷场测试评估认知功能；通过蛋白质印迹法评估海马突触后密度蛋白95和突触素；通过免疫组织化学评估毛细血管的星形细胞覆盖、小胶质细胞活化和结构毛细血管密度。 结果早期适度的体育锻炼能够使功能性毛细血管密度正常化，并减少慢性脑灌注不足动物大脑中的白细胞滚动。这些作用伴随着突触蛋白的恢复和认知功能的改善。此外，早期适度运动可改善大脑皮层和海马体血管中星形胶质细胞的覆盖，减少海马体中小胶质细胞的活化，改善海马体中的毛细血管结构。结论 大脑微循环和炎症变化似乎与引发慢性脑缺血动物的认知能力下降有关。因此，早期干预体育锻炼可能是预防慢性脑灌注不足引起的神经退行性疾病的方法。