What question did this study set out to answer?

To explore the effects of exercise on cerebral microvascular density and angiogenic signaling in aging brains.

March 1, 2026In Vivo0 citationsOpen Access

Protective Effect of Exercise Training Against Age-induced Cerebral Microvascular Rarefaction: VEGF/Flk-1/PI3K/Akt Signaling and GLUT1 Expression

SVSheepsumon Viboolvorakul DBDecha Buranajitpirom SPSUTHILUK PATUMRAJ

Key Points

To explore the effects of exercise on cerebral microvascular density and angiogenic signaling in aging brains.
Group division of male rats: age-matched control, sedentary control, and exercise-trained.
Swimming exercise was performed by the exercise-trained group.
Regional cerebral tissue perfusion (CTP) assessed using <i>in vivo</i> methods.
Immunohistochemical staining of GLUT1 to measure microvessel density and metabolic state.
Immunoassays of VEGF proteins conducted on isolated brain microvessels.
Sedentary control group showed significantly reduced microvessel density and CTP compared to age-matched control.
Exercise training led to substantial increases in microvessel density and CTP in comparison to the sedentary group.
Exercise indicated an increase in GLUT1, showing restored endothelial metabolic function.
VEGF levels were lower in the sedentary group but significantly increased with exercise training.
Positive correlation found among microvessel density, CTP, and VEGF levels across all groups.

Abstract

Background/Aim: Age-related cerebral microvascular loss is associated with reduced angiogenesis and leads to inadequate tissue perfusion in the brain. Vascular endothelial growth factor (VEGF), crucial for angiogenesis, declines with age. Exercise enhances microvascular density and blood flow, promoting brain health. The specific mechanisms underlying exercise-induced angiogenesis in aging brains remain unclear. This study investigated the impact of exercise on microvessel density, tissue perfusion, and VEGF-angiogenic signaling in aging brains. Materials and Methods: Male rats were divided into three groups: an age-matched control, a sedentary control, and an exercise-trained group, which underwent swimming exercise. Regional cerebral tissue perfusion (CTP) was assessed in an in vivo study. Brain immunohistochemical staining of glucose transporter-1 (GLUT1) was used to determine microvessel density and endothelial metabolic state. Immunoassays of VEGF angiogenic proteins in isolated brain microvessels were conducted to reveal microvascular signaling mechanisms. Results: Microvessel density and regional CTP in the sedentary control group were significantly reduced compared to the age-matched control group. The exercise-trained group demonstrated substantial increases in microvessel density and regional CTP compared to the sedentary control group. An increase in GLUT1 in the exercise group indicates microvascular metabolic restoration. VEGF angiogenic protein levels were significantly decreased in the sedentary control group compared to the age-matched control group; however, exercise training significantly increased these protein levels relative to the sedentary control group. Furthermore, we discovered a strong and significant positive correlation among the microvessel density, regional CTP, and VEGF angiogenic proteins across the three groups. Conclusion: Swimming exercise training may protect against age-induced cerebral microvascular loss and insufficient brain tissue perfusion through the VEGF-mediated angiogenic signaling cascade. The increase in GLUT1 indicates restored structural and metabolic endothelial function in the aging brain.

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