Central Neurobiological Mechanisms of Acupuncture in Post-Stroke Depression: Multi-Target and Network-Based Regulation

Jing Cao,1– 4,* Yangyang Xu,1– 4,* Huifang Mao,1– 4 Jianbei Chen,5 Deguang Ding,1– 4 Xinyin Xu5 1Acupuncture and Moxibustion Center, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, Hubei Province, 430065, People’s Republic of China; 2Hubei Provincial Clinical Research Center for Acupuncture and Moxibustion in Obesity Treatment, Wuhan, Hubei Province, 430065, People’s Republic of China; 3Acupuncture and Moxibustion Center, Affiliated Hospital of Hubei University of Chinese Medicine, Wuhan, Hubei Province, 430065, People’s Republic of China; 4Hubei Shizhen Laboratory, Wuhan, Hubei Province, 430065, People’s Republic of China; 5First Clinical Medical College,Hubei University of Chinese Medicine, Wuhan, Hubei Province, 430070,People’s Republic of China*These authors contributed equally to this workCorrespondence: Deguang Ding, Acupuncture and Moxibustion Center, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, Hubei Province, 430065, People’s Republic of China, Tel +8615327262567, Email [email protected] Xinyin Xu, First Clinical Medical College, Hubei University of Chinese Medicine, Wuhan, Hubei Province, 430070, People’s Republic of China, Tel +8613517191258, Email [email protected]: Post-stroke depression (PSD) is a common post-stroke complication with limited treatment options and significant adverse effects from conventional drugs. Acupuncture, a multi-target holistic non-pharmacological intervention, shows unique clinical advantages. This review provides the first systematic synthesis of the central neurobiological mechanisms underlying acupuncture’s therapeutic effects on PSD. The identified mechanisms include promoting neuroplasticity via the BDNF/TrkB pathway and rebalancing neurotransmitter systems (monoamines and glutamate/GABA). Additionally, acupuncture inhibits microglial activation and TLR4/NF-κB/NLRP3-driven neuroinflammation, restores mitochondrial homeostasis through AMPK-dependent autophagy, and modulates the gut microbiota–brain axis. Together, these findings elucidate the “multi-target, network-based” characteristics of acupuncture from a modern scientific perspective, providing a scientific basis for traditional Chinese acupuncture principles. By integrating recent mechanistic advances, this review addresses literature gaps and offers a theoretical foundation for optimizing clinical strategies, promoting mechanism-driven personalized interventions, and bridging traditional Chinese medicine with contemporary neuroscience.Keywords: post-stroke depression, acupuncture, electroacupuncture, neurobiology, mitochondrial function, gut–brain axis