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 t...

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Main Authors: Marina Leardini-Tristão, Giulia Andrade, Celina Garcia, Patrícia A. Reis, Millena Lourenço, Emilio T. S. Moreira, Flavia R. S. Lima, Hugo C. Castro-Faria-Neto, Eduardo Tibirica, Vanessa Estato
Format: Article
Language:English
Published: BMC 2020-04-01
Series:Journal of Neuroinflammation
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Online Access:http://link.springer.com/article/10.1186/s12974-020-01771-y
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author Marina Leardini-Tristão
Giulia Andrade
Celina Garcia
Patrícia A. Reis
Millena Lourenço
Emilio T. S. Moreira
Flavia R. S. Lima
Hugo C. Castro-Faria-Neto
Eduardo Tibirica
Vanessa Estato
author_facet Marina Leardini-Tristão
Giulia Andrade
Celina Garcia
Patrícia A. Reis
Millena Lourenço
Emilio T. S. Moreira
Flavia R. S. Lima
Hugo C. Castro-Faria-Neto
Eduardo Tibirica
Vanessa Estato
author_sort Marina Leardini-Tristão
collection DOAJ
description 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. 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.
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spelling doaj.art-ec087e933c9541d59c42a0c5912f59652022-12-21T18:57:17ZengBMCJournal of Neuroinflammation1742-20942020-04-0117111410.1186/s12974-020-01771-yPhysical exercise promotes astrocyte coverage of microvessels in a model of chronic cerebral hypoperfusionMarina Leardini-Tristão0Giulia Andrade1Celina Garcia2Patrícia A. Reis3Millena Lourenço4Emilio T. S. Moreira5Flavia R. S. Lima6Hugo C. Castro-Faria-Neto7Eduardo Tibirica8Vanessa Estato9Laboratory of Immunopharmacology, Oswaldo Cruz FoundationLaboratory of Immunopharmacology, Oswaldo Cruz FoundationLaboratory of Glial Cell Biology, Biomedical Sciences Institute, Federal University of Rio de JaneiroLaboratory of Immunopharmacology, Oswaldo Cruz FoundationLaboratory of Immunopharmacology, Oswaldo Cruz FoundationLaboratory of Immunopharmacology, Oswaldo Cruz FoundationLaboratory of Glial Cell Biology, Biomedical Sciences Institute, Federal University of Rio de JaneiroLaboratory of Immunopharmacology, Oswaldo Cruz FoundationLaboratory of Cardiovascular Investigation, Oswaldo Cruz FoundationLaboratory of Immunopharmacology, Oswaldo Cruz FoundationAbstract 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.http://link.springer.com/article/10.1186/s12974-020-01771-yExerciseCerebral hypoperfusionNeuroinflammationGlial cellsMicrocirculation
spellingShingle Marina Leardini-Tristão
Giulia Andrade
Celina Garcia
Patrícia A. Reis
Millena Lourenço
Emilio T. S. Moreira
Flavia R. S. Lima
Hugo C. Castro-Faria-Neto
Eduardo Tibirica
Vanessa Estato
Physical exercise promotes astrocyte coverage of microvessels in a model of chronic cerebral hypoperfusion
Journal of Neuroinflammation
Exercise
Cerebral hypoperfusion
Neuroinflammation
Glial cells
Microcirculation
title Physical exercise promotes astrocyte coverage of microvessels in a model of chronic cerebral hypoperfusion
title_full Physical exercise promotes astrocyte coverage of microvessels in a model of chronic cerebral hypoperfusion
title_fullStr Physical exercise promotes astrocyte coverage of microvessels in a model of chronic cerebral hypoperfusion
title_full_unstemmed Physical exercise promotes astrocyte coverage of microvessels in a model of chronic cerebral hypoperfusion
title_short Physical exercise promotes astrocyte coverage of microvessels in a model of chronic cerebral hypoperfusion
title_sort physical exercise promotes astrocyte coverage of microvessels in a model of chronic cerebral hypoperfusion
topic Exercise
Cerebral hypoperfusion
Neuroinflammation
Glial cells
Microcirculation
url http://link.springer.com/article/10.1186/s12974-020-01771-y
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