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Neuroprotective mechanism of acupuncture against brain injury during delayed thrombolysis for acute ischemic stroke.

Journal of integrative medicine·March 2026·Zheng Huang, Xin-Yu Liu, Jun-Feng Gao et al.
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Key Finding

Acupuncture protected against ferroptosis-induced brain injury in delayed stroke thrombolysis by upregulating anti-ferroptosis proteins SLC7A11 and GPX4, with serum iron levels negatively correlating with stroke severity (r=-0.709) and predicting hemorrhagic complications (AUC=0.803).

What This Means For You

Researchers investigated whether acupuncture could protect the brain when stroke patients receive clot-busting treatment later than the standard 3-hour window. The study combined animal experiments, patient data analysis, and advanced laboratory techniques to understand how delayed thrombolysis (clot-dissolving medication) might cause additional brain damage through a process called ferroptosis—a type of cell death involving iron buildup and tissue damage.

The research team examined 80 stroke patients and 30 healthy volunteers, comparing outcomes between those who received thrombolysis within 3 hours versus those treated between 4.5-6 hours after stroke onset. They found that delayed treatment triggered ferroptosis, marked by changes in iron metabolism and increased risk of brain bleeding. Lower serum iron levels correlated with worse stroke severity and higher bleeding risk.

In rat studies, acupuncture showed significant protective effects when combined with delayed thrombolysis. It reduced harmful iron accumulation, decreased oxidative stress markers, and protected the blood-brain barrier from damage. Acupuncture worked by regulating key proteins involved in ferroptosis—increasing protective proteins (SLC7A11 and GPX4) while decreasing harmful ones (ACSL4). This led to improved mitochondrial health, better neurological function, and reduced brain injury.

For patients, these findings suggest acupuncture may be a valuable complementary therapy for acute stroke, particularly when thrombolysis must be delayed beyond the optimal time window. The treatment appears to enhance safety by preventing ferroptosis-related complications. If considering acupuncture for stroke recovery, seek care from a licensed acupuncturist experienced in neurological conditions and integrated stroke care.

Clinical Notes for Practitioners

This multi-modal study investigated acupuncture's neuroprotective mechanisms against ferroptosis in delayed acute ischemic stroke (AIS) thrombolysis. Researchers employed transcriptomic/proteomic analysis, clinical retrospective review (n=110: 80 AIS patients stratified by thrombolysis timing <3h vs 4.5-6h, plus 30 controls), and rat thromboembolic stroke models with 6-hour delayed rt-PA administration.

Clinical findings revealed reduced serum iron and transferrin levels in AIS patients, with serum iron negatively correlating with NIHSS scores (r=-0.709, P<0.01) and demonstrating highest predictive efficacy for symptomatic intracerebral hemorrhage (AUC=0.803). Multi-omics analysis identified ferroptosis pathway enrichment involving glutamate metabolism and lipid peroxidation.

In vivo experiments demonstrated acupuncture upregulated anti-ferroptosis proteins SLC7A11 and GPX4 while downregulating pro-ferroptosis ACSL4. Treatment reduced iron deposition and MDA content, increased GSH levels, improved mitochondrial integrity, protected BBB disruption, and enhanced neurological outcomes. Acupuncture showed synergistic effects with liproxstatin-1.

Clinical implications: Acupuncture represents a promising adjunctive non-pharmacological intervention to enhance delayed thrombolysis safety by modulating ferroptosis pathways and preserving neurovascular integrity.

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