Acupuncture regulates astrocyte neurotoxic polarization to protect blood–brain barrier integrity in delayed thrombolysis through mediating ERK1/2/Cx43 axis

IF 2 Q3 NEUROSCIENCES

IBRO Neuroscience Reports Pub Date : 2025-04-11 DOI:10.1016/j.ibneur.2025.04.005

Zhi-Hui Zhang , Yu Gu , Zheng Huang , Xin-Yu Liu , Wen-Tao Xu , Xin-Chang Zhang , Guang-Xia Ni

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Abstract

Background

Thrombolytic therapy remains the standard treatment for acute ischemic stroke. The narrow window for thrombolysis means that delay in treatment worsens brain injury. Astrocytes regulate blood-brain barrier (BBB) integrity and neuroinflammation, yet their neurotoxic polarization exacerbates injury in neuropathological conditions, including ischemic stroke. Delayed recombinant tissue plasminogen activator (rt-PA) thrombolysis disrupts astrocyte homeostasis, further aggravating brain injury. This study investigates whether acupuncture, a key therapy in traditional Chinese medicine, alleviates delayed thrombolysis-induced injury by modulating astrocyte neurotoxic polarization and elucidates the underlying signaling pathway.

Methods

A rat model of embolic stroke with delayed rt-PA thrombolysis was established. The effects of infarct volume, BBB integrity, and neuroinflammation of acupuncture were evaluated. Bulk and single-cell transcriptomic analyses were performed to assess astrocyte-specific transcriptional changes. Western blotting, immunofluorescence, and pharmacological inhibition experiments validated molecular mechanisms.

Results

Acupuncture reduced infarct volume, improved neurological function, and restored BBB integrity. Transcriptomic analysis revealed dynamic regulation of astrocyte neurotoxic polarization following acupuncture intervention. Further validation experiments demonstrated that acupuncture suppressed the ERK1/2-Cx43 cascade, thereby attenuating astrocyte-mediated neurotoxicity. Pharmacological modulation of this pathway replicated the protective effects of acupuncture, highlighting the role in mitigating astrocyte dysfunction and promoting BBB recovery.

Conclusion

Acupuncture mitigates delayed thrombolysis-induced brain injury by modulating astrocyte polarization via the ERK1/2-Cx43 pathway. These findings highlight acupuncture as a potential strategy to enhance thrombolytic therapy safety in ischemic stroke.

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针灸通过介导 ERK1/2/Cx43 轴调节星形胶质细胞神经毒性极化，保护延迟溶栓中血脑屏障的完整性

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