Novel insights of acupuncture in ischemic stroke: orchestrating neuro-endocrine-immune network

Ischemic stroke (IS) is a major public health challenge with high rates of mortality and disability. Its pathophysiology is complex and multifactorial. Although the pathogenesis of IS originates from local cerebral ischemia, it progresses to a systemic disorder involving dysfunction of the neuro-endocrine-immune (NEI) network. Acupuncture, a non-pharmaceutical therapy characterized by holistic regulation, holds considerable potential for correcting multi-system imbalances after IS. Nevertheless, how acupuncture coordinates this multi-system network remains poorly understood. This review synthesizes current evidence on the cellular and molecular mechanisms underlying acupuncture's regulation of neural signaling, hormonal homeostasis, and inflammatory responses following IS. Notably, we clarify how acupuncture modulates the NEI network via the cholinergic anti-inflammatory pathway and the brain-gut axis, emphasizing its multi-system synergistic effects. In addition, we analyze the main challenges in this field and look forward to the prospects. This comprehensive perspective provides new insights into the mechanism of acupuncture for IS, signifying a transition from empirical treatment to precision medicine.