The role of exercise in enhancing brain and cerebrovascular health via the bone–brain axis: implications for surgical and clinical interventions

作者：Haojun Shi, Lei Huang, Qian Wang, Nan Zhang, Cui Lv, Chengshou Lin, Litao Shao, Dongshuai Xia, Zhijie Zhao, Guang Yang, Weijian Chen, Zhiwei Li, John H. Zhang, Gongchang Yu, Liang Shi, Yisheng Chen · 发表于：International Journal of Surgery · 年份：2025 · DOI：10.1097/js9.0000000000003030 · 被引用次数：9 · 研究领域：Anesthesia and Neurotoxicity Research、Traumatic Brain Injury and Neurovascular Disturbances、Osteoarthritis Treatment and Mechanisms

Abstract The bone–brain axis constitutes an interactive bidirectional signaling network integrating skeletal, neural, and muscular systems, serving critical functions across both normal physiological operations and disease mechanisms. Exercise, a non-pharmacological intervention, significantly influences this axis by enhancing bone-derived factors like osteocalcin, which in turn affect cognitive function, neuroplasticity, and systemic metabolism. This review delves into the molecular and cellular mechanisms underlying the bone–brain axis, with a particular focus on exercise-induced pathways. Physical activity stimulates the secretion of myogenic and neuromodulatory mediators including brain-derived neurotrophic factor (BDNF) and irisin, which augment synaptic adaptability, suppress inflammatory responses, and facilitate neuronal regeneration. These effects are critical in alleviating neurodegenerative diseases, osteoporosis, and mood disorders. The review also examines the endocrine role of bone-derived factors like uncarboxylated osteocalcin and sclerostin in modulating neurotransmitter synthesis and neuroimmune responses, including regulating osteoblast activity and bone remodeling, stimulating BDNF expression in the brain, regulating bone marrow-derived macrophages, and modulating cytokine pathways to alleviate neuroinflammation. Findings suggest that the bone–brain axis not only mitigates age-related degeneration but also holds therapeutic potential for chronic disease ma...