# Acupuncture Alleviates Blood–Brain Barrier Damage After Delayed rtPA Thrombolysis for Acute Ischemic Stroke by Regulating Ferroptosis

## TL;DR

Acupuncture helps reduce brain damage after delayed stroke treatment by preventing a type of cell death called ferroptosis.

## Contribution

This study shows acupuncture protects the blood-brain barrier by inhibiting ferroptosis after delayed rtPA treatment in stroke.

## Key findings

- XNKQ acupuncture reduced infarct volume, brain edema, and hemorrhagic transformation in rats.
- Acupuncture preserved mitochondrial structure and inhibited lipid peroxidation and iron metabolism disorders.
- The treatment improved neurological function and blood-brain barrier integrity after delayed rtPA.

## Abstract

Acute ischemic stroke (AIS) is the second leading cause of death and disability worldwide. Recombinant tissue plasminogen activator (rtPA) was the first FDA‐approved thrombolytic drug for AIS. However, delayed administration of rtPA exacerbates brain injury and increases the risk of hemorrhagic transformation (HT) and mortality. Ferroptosis, an iron‐dependent form of cell death, is closely associated with the pathological process of AIS. Acupuncture, a vital component of traditional Chinese medicine, has been widely used in clinical practice for AIS treatment. This study aims to investigate the protective effects of acupuncture on rats subjected to delayed rtPA thrombolysis in cerebral infarction and its relationship with ferroptosis.

Adult male Sprague‐Dawley rats were used to establish a thromboembolic stroke model and were randomly assigned to different treatment groups. Xingnao Kaiqiao (XNKQ) acupuncture (at Neiguan and Shuigou acupoints) or sham acupuncture was administered in combination with rtPA thrombolysis. Outcome measures included neurological scores, infarct volume, brain water content, blood–brain barrier (BBB) permeability, expression of iron metabolism‐related proteins, lipid peroxidation levels, and mitochondrial ultrastructural changes.

XNKQ acupuncture significantly improved neurological deficits following delayed rtPA thrombolysis, reduced infarct volume and brain water content, and decreased the incidence of HT and brain edema. By modulating iron metabolism, inhibiting lipid peroxidation, and preserving mitochondrial integrity, acupuncture attenuated neuronal damage and BBB disruption mediated by ferroptosis.

XNKQ acupuncture inhibits neuronal ferroptosis by improving iron metabolism disorders, lipid peroxidation accumulation, and mitochondrial structure, thereby alleviating neuronal damage and BBB disruption, and exerting a protective effect on brain tissue after delayed rtPA thrombolysis.

This study established a rat model of thromboembolic stroke to investigate the effect of Xingnao Kaiqiao acupuncture combined with delayed rtPA thrombolysis. The results showed that acupuncture could alleviate neuronal ferroptosis, improve blood‐brain barrier injury, protect neurological function and reduce the risk of hemorrhagic transformation by regulating iron metabolism, inhibiting lipid peroxidation and protecting mitochondrial structure.