Table 1_Effects and mechanisms of transcutaneous auricular vagus nerve stimulation on post-stroke cognitive impairment in animal studies: a systematic review and meta-analysis.xlsx

The meta-analysis revealed that taVNS significantly improved memory function in PSCI animals (SMD = 1.85, 95% CI: 1.06 to 2.64, p < 0.01, I ² = 57%) and learning ability (MD = − 6.38, 95% CI: − 8.87 to − 3.89, p < 0.01, I ² = 0%) and reduced modified neurological severity scores (MD = − 1.08, 95% CI: − 1.63 to − 0.52, p < 0.01, I ² = 38%). Mechanistically, taVNS significantly elevated acetylcholine levels (SMD = 1.57, 95% CI: 0.85 to 2.30, p < 0.01, I² = 0%), inhibited neuronal apoptosis (SMD = 2.29), and promoted angiogenesis (SMD = 1.63).

Sensitivity analysis confirmed the robustness of the primary outcomes.</p>Conclusion<p>This study provides preclinical evidence confirming that taVNS can effectively improve cognitive deficits in PSCI animal models. The enhancement of Ach levels, inhibition of neuronal apoptosis, and promotion of vascular repair may be related to the non-neuronal cholinergic system (NNCS), anti-inflammatory, and antioxidant stress mechanisms.

However, as only a few studies were included, more high-quality animal experiments are needed in the future to develop standardized interventions and further explore the molecular mechanisms underlying these effects.</p>Systematic review registration<p>crd.york.ac.uk/prospero/display_record.php?ID=CRD420261329420.</p>