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<p>Functional recovery after cerebral ischemia-reperfusion injury (CIRI) depends on synaptic plasticity, which is profoundly modulated by astrocyte phenotypes—the neurotoxic A1 phenotype exacerbates damage, while the A2 phenotype supports repair. Electroacupuncture (EA) is neuroprotective, yet whether it promotes synaptic repair by orchestrating this phenotypic switch remains elusive. We hypothesized that EA drives this switch via the SIRT1–NF-κB axis to enhance synaptic recovery.&#xa0;Mice that underwent middle cerebral artery occlusion/reperfusion (MCAO/R) were randomly assigned to the following experimental groups: MCAO/R, EA, EA + SIRT1 inhibitor (Selisistat), or MCAO/R + NF-κB inhibitor (PDTC). Sham-operated mice served as Sham group. EA at GV20 and GV16 was applied daily for 7 days. Neurological function, cerebral blood flow, SIRT1 activity, NF-κB pathway, astrocyte markers (C3, S100A10), inflammatory cytokines, and synaptic proteins were assessed using behavioral tests, imaging, Western blotting, immunofluorescence, ELISA, and transmission electron microscopy.&#xa0;EA significantly improved neurological function and cerebral blood flow. Notably, EA upregulated both the protein level and deacetylase activity of SIRT1 while concurrently suppressing NF-κB phosphorylation, indicating a shift toward anti-inflammatory signaling. This molecular change was accompanied by a significant reduction in the A1 astrocytic marker C3 and pro-inflammatory cytokines, alongside a pronounced increase in the A2 marker S100A10 and anti-inflammatory mediators. Furthermore, EA restored synaptic protein expression and preserved synaptic ultrastructural integrity. The SIRT1 inhibitor Selisistat reversed all these beneficial effects, whereas the NF-κB inhibitor PDTC phenocopied EA‑induced astrocyte phenotype modulation.&#xa0;EA drives astrocyte phenotypic switching from A1 to A2 via the SIRT1–NF-κB axis, reshaping the inflammatory microenvironment to promote synaptic repair and functional recovery after CIRI.</p>

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Electroacupuncture Promotes Synaptic Recovery After Cerebral Ischemia-Reperfusion by Activating SIRT1 to Inhibit the NF-κB Pathway and Regulate Astrocyte Phenotypic Transformation

  • 期刊论文

  • 发表日期：

    2026年5月18日

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  • Qing Song,
  • Meng-Meng Zhao,
  • Wen-Qiang Sun,
  • Qian-Yun Xie,
  • Yang Zhang,
  • Wei Tang,
  • Meng-Xing Li

摘要

Functional recovery after cerebral ischemia-reperfusion injury (CIRI) depends on synaptic plasticity, which is profoundly modulated by astrocyte phenotypes—the neurotoxic A1 phenotype exacerbates damage, while the A2 phenotype supports repair. Electroacupuncture (EA) is neuroprotective, yet whether it promotes synaptic repair by orchestrating this phenotypic switch remains elusive. We hypothesized that EA drives this switch via the SIRT1–NF-κB axis to enhance synaptic recovery. Mice that underwent middle cerebral artery occlusion/reperfusion (MCAO/R) were randomly assigned to the following experimental groups: MCAO/R, EA, EA + SIRT1 inhibitor (Selisistat), or MCAO/R + NF-κB inhibitor (PDTC). Sham-operated mice served as Sham group. EA at GV20 and GV16 was applied daily for 7 days. Neurological function, cerebral blood flow, SIRT1 activity, NF-κB pathway, astrocyte markers (C3, S100A10), inflammatory cytokines, and synaptic proteins were assessed using behavioral tests, imaging, Western blotting, immunofluorescence, ELISA, and transmission electron microscopy. EA significantly improved neurological function and cerebral blood flow. Notably, EA upregulated both the protein level and deacetylase activity of SIRT1 while concurrently suppressing NF-κB phosphorylation, indicating a shift toward anti-inflammatory signaling. This molecular change was accompanied by a significant reduction in the A1 astrocytic marker C3 and pro-inflammatory cytokines, alongside a pronounced increase in the A2 marker S100A10 and anti-inflammatory mediators. Furthermore, EA restored synaptic protein expression and preserved synaptic ultrastructural integrity. The SIRT1 inhibitor Selisistat reversed all these beneficial effects, whereas the NF-κB inhibitor PDTC phenocopied EA‑induced astrocyte phenotype modulation. EA drives astrocyte phenotypic switching from A1 to A2 via the SIRT1–NF-κB axis, reshaping the inflammatory microenvironment to promote synaptic repair and functional recovery after CIRI.