Exercise Improves Cerebral Blood Flow and Functional Outcomes in an Experimental Mouse Model of Vascular Cognitive Impairment and Dementia (VCID)
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature..
Vascular cognitive impairment and dementia (VCID) are a growing threat to public health without any known treatment. The bilateral common carotid artery stenosis (BCAS) mouse model is valid for VCID. Previously, we have reported that remote ischemic postconditioning (RIPostC) during chronic cerebral hypoperfusion (CCH) induced by BCAS increases cerebral blood flow (CBF), improves cognitive function, and reduces white matter damage. We hypothesized that physical exercise (EXR) would augment CBF during CCH and prevent cognitive impairment in the BCAS model. BCAS was performed in C57/B6 mice of both sexes to establish CCH. One week after the BCAS surgery, mice were randomized to treadmill exercise once daily or no EXR for four weeks. CBF was monitored with an LSCI pre-, post, and 4 weeks post-BCAS. Cognitive testing was performed for post-BCAS after exercise training, and brain tissue was harvested for histopathology and biochemical test. BCAS led to chronic hypoperfusion resulting in impaired cognitive function and other functional outcomes. Histological examination revealed that BCAS caused changes in neuronal morphology and cell death in the cortex and hippocampus. Immunoblotting showed that BCAS was associated with a significant downregulate of AMPK and pAMPK and NOS3 and pNOS3. BCAS also decreased red blood cell (RBC) deformability. EXR therapy increased and sustained improved CBF and cognitive function, muscular strength, reduced cell death, and loss of white matter. EXR is effective in the BCAS model, improving CBF and cognitive function, reducing white matter damage, improving RBC deformability, and increasing RBC NOS3 and AMPK. The mechanisms by which EXR improves CBF and attenuates tissue damage need further investigation.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Translational stroke research - 15(2024), 2 vom: 17. März, Seite 446-461 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Khan, Mohammad Badruzzaman [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 26.02.2024 Date Revised 20.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s12975-023-01124-w |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Vascular cognitive impairment and dementia (VCID) are a growing threat to public health without any known treatment. The bilateral common carotid artery stenosis (BCAS) mouse model is valid for VCID. Previously, we have reported that remote ischemic postconditioning (RIPostC) during chronic cerebral hypoperfusion (CCH) induced by BCAS increases cerebral blood flow (CBF), improves cognitive function, and reduces white matter damage. We hypothesized that physical exercise (EXR) would augment CBF during CCH and prevent cognitive impairment in the BCAS model. BCAS was performed in C57/B6 mice of both sexes to establish CCH. One week after the BCAS surgery, mice were randomized to treadmill exercise once daily or no EXR for four weeks. CBF was monitored with an LSCI pre-, post, and 4 weeks post-BCAS. Cognitive testing was performed for post-BCAS after exercise training, and brain tissue was harvested for histopathology and biochemical test. BCAS led to chronic hypoperfusion resulting in impaired cognitive function and other functional outcomes. Histological examination revealed that BCAS caused changes in neuronal morphology and cell death in the cortex and hippocampus. Immunoblotting showed that BCAS was associated with a significant downregulate of AMPK and pAMPK and NOS3 and pNOS3. BCAS also decreased red blood cell (RBC) deformability. EXR therapy increased and sustained improved CBF and cognitive function, muscular strength, reduced cell death, and loss of white matter. EXR is effective in the BCAS model, improving CBF and cognitive function, reducing white matter damage, improving RBC deformability, and increasing RBC NOS3 and AMPK. The mechanisms by which EXR improves CBF and attenuates tissue damage need further investigation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a AMPK | |
| 650 | 4 | |a Chronic cerebral hypoperfusion | |
| 650 | 4 | |a Exercise (EXR), Cerebral blood flow (CBF) | |
| 650 | 4 | |a Neurobehavioral test | |
| 650 | 4 | |a Phospho-AMPK | |
| 650 | 4 | |a RBC deformability, White matter (WM) degeneration, Nitric oxide synthase (NOS3) | |
| 650 | 4 | |a Vascular cognitive impairment and dementia (VCID) | |
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