Research progress on the mechanism of acupuncture in treatment of ischemic stroke

Ischemic stroke is one of the leading causes of death and disability worldwide, affecting millions of people each year. This comprehensive review examines the mechanisms by which acupuncture exerts its therapeutic effects in the treatment of ischemic stroke, revealing a complex and multifaceted landscape of neuroprotective actions. The research demonstrates that acupuncture acts through multiple biological pathways simultaneously, offering a unique and promising therapeutic approach.

One of the best-documented mechanisms is modulation of the inflammatory response. After ischemic stroke, the brain develops intense neuroinflammation that can worsen neuronal damage. Acupuncture demonstrates a notable capacity to regulate microglial activation, promoting the conversion of pro-inflammatory microglia (M1) to the anti-inflammatory phenotype (M2). Studies show that electroacupuncture at points such as Baihui (GV-20) and Dazhui (GV-14) significantly increases the expression of anti-inflammatory factors such as IL-10 and TGF-β, while reducing pro-inflammatory cytokines such as IL-1β and TNF-α.

In addition, acupuncture inhibits the NLRP3 inflammasome and the NF-κB pathway, blocking harmful inflammatory cascades.

Protection against programmed cell death represents another crucial mechanism. The review identifies four main cell-death pathways that acupuncture can modulate: apoptosis, autophagy, pyroptosis, and ferroptosis. In apoptosis, acupuncture increases expression of the anti-apoptotic protein Bcl-2 while reducing pro-apoptotic factors such as Bax and caspase-3. Interestingly, it also acts through epigenetic modifications, altering histone acetylation at the promoters of these genes.

With respect to autophagy, acupuncture demonstrates an intelligent bidirectional effect, promoting beneficial autophagy in the early stages (to clear cellular debris) and inhibiting excessive autophagy at later stages through the PI3K/AKT/mTOR pathway.

Counteracting oxidative stress is central to the neuroprotection offered by acupuncture. The brain is particularly vulnerable to damage from reactive oxygen species (ROS), and acupuncture demonstrates a capacity to restore oxidative balance. It increases superoxide dismutase (SOD) activity, raises glutathione levels, and reduces lipid peroxidation. These effects are mediated by activation of the PGC-1α/NRF1/TFAM pathway, which improves mitochondrial biogenesis and cellular energy metabolism.

Promotion of angiogenesis represents a crucial regenerative aspect of acupuncture therapy. Through activation of the VEGF and EPO-Src pathways, acupuncture stimulates the formation of new blood vessels in the peri-infarct area. This improves cerebral perfusion and provides essential vascular support for neuronal recovery. The VEGF/Notch pathway is also activated, promoting endothelial cell survival and sustained angiogenesis.

Perhaps the most fascinating aspect is acupuncture's capacity to improve synaptic plasticity. The review shows that acupuncture acts on both structural and functional plasticity of synapses. Structurally, it increases synaptic density, postsynaptic density thickness, and the number of synaptic vesicles. Functionally, it improves long-term potentiation (LTP) in the hippocampus, which is essential for learning and memory.

These effects are mediated by regulation of key proteins such as BDNF, synaptophysin, and PSD-95, through pathways such as BDNF/TrkB/CREB and CaM-CaMKII.

The clinical implications are substantial. The multitarget nature of acupuncture offers advantages over therapies that aim at a single mechanism, potentially explaining its clinical efficacy across diverse post-stroke deficits. The capacity to simultaneously modulate inflammation, cell death, oxidative stress, and neural regeneration suggests that acupuncture may be particularly valuable as adjunctive therapy.

There are, however, important limitations. Most studies examine mechanisms in isolation, without considering their complex interactions. Much of the research relies solely on protein expression, without functional validation through specific inhibitors or agonists. In addition, there is a need to standardize acupuncture protocols and determine optimal timing of intervention.

This review establishes a solid scientific basis for the use of acupuncture in ischemic stroke, revealing sophisticated mechanisms that justify its observed clinical efficacy. Future research should focus on integrating these mechanisms and optimizing therapeutic protocols to maximize clinical benefits.