Physical exercise promotes astrocyte coverage of microvessels in a model of chronic cerebral hypoperfusion

Abstract

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.(Continued on next page) (Continued from previous page)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.

Exercise‐Linked Irisin Prevents Mortality and Enhances Cognition in a Mice Model of Cerebral Ischemia by Regulating Klotho Expression

“…It has been demonstrated that exercise exerts a protective effect on cerebral ischemia-reperfusion injury and Alzheimer's disease [ 5 ], and irisin, as a critical peptide in the body, can be secreted by skeletal muscle and brain tissue after exercise [ 26 ]. This leads our study to observe whether physical exercise and exogenous irisin have the same neuroprotective effects on cerebral ischemia and whether irisin contributes to the neuroprotective effects of physical exercise.…”

“…It is well-established that physical exercise can exert neuroprotective effects on some neurological disorders, with the underlying mechanism remained to be elucidated [ 5 , 6 ]. Irisin, which can be released into circulation after physical exercise, is identified as a myokine [ 7 ].…”

Dl-3-n-Butylphthalide Alleviates Hippocampal Neuron Damage in Chronic Cerebral Hypoperfusion via Regulation of the CNTF/CNTFRα/JAK2/STAT3 Signaling Pathways

“…A substantial amount of evidence indicates that CCH, a chronic, moderate, and persistent reduction in CBF, leads to the development and progression of cognitive impairments (Cechetti et al, 2012 ; Li et al, 2019a , b ); this type of dementia is classified as VD, which represents the second most common form of dementia after AD (Han et al, 2020 ; Leardini-Tristão et al, 2020 ). Despite the importance of treating CCH in aging societies, apart from improving cerebral perfusion (Li et al, 2019c ) and controlling other risk factors, there is no definite treatment for CCH-related cognitive damage (Kim et al, 2020 ).…”

Long‐term environmental enrichment reduces microglia morphological diversity of the molecular layer of dentate gyrus

“…Many studies have shown that environmental enrichment including voluntary exercise and somatomotor and visuospatial stimulation is capable of promoting the modulation of cytokines (Pedersen, 2009) and chemokines (Trøseid et al, 2004), natural killer cells (Benaroya‐Milshtein et al, 2004), and T lymphocytes mobilization (Marashi, Barnekow, Ossendorf, & Sachser, 2003; de Sousa et al, 2011; Singhal et al, 2020), microglia (Gomes et al., 2019; de Sousa et al., 2015) and astrocytes numerical and morphological changes (Diniz et al, 2010; Diniz, Silva, et al, 2016; Leardini‐Tristão et al, 2020; Singhal et al, 2020) and neurogenesis (Valero, Paris, & Sierra, 2016; Wasinski, Batista, Bader, Araujo, & Klempin, 2018). Bi‐directional cross talk between microglia, astrocytes and neurons (Singhal et al, 2020; Kofuji & Araque, 2020) are key elements to achieve homeostatic conditions, and chemokine signaling seems to be essential to orchestrate communication among them, preserving brain function (Trettel, Di Castro, & Limatola, 2019).…”