Acupuncture Alleviates Blood–Brain Barrier Damage After Delayed rtPA Thrombolysis for Acute Ischemic Stroke by Regulating Ferroptosis
ABSTRACT Background 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...
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| Format: | Article |
| Language: | English |
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Wiley
2025-07-01
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| Series: | Brain and Behavior |
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| Online Access: | https://doi.org/10.1002/brb3.70644 |
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| author | Zheng Huang Tianliang Lu Xinyu Liu Zhihui Zhang Yangyang Song Yiyang Li Wentao Xu Xinchang Zhang Guangxia Ni |
| author_facet | Zheng Huang Tianliang Lu Xinyu Liu Zhihui Zhang Yangyang Song Yiyang Li Wentao Xu Xinchang Zhang Guangxia Ni |
| author_sort | Zheng Huang |
| collection | DOAJ |
| description | ABSTRACT Background 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. Methods 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. Results 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. Conclusion 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. |
| format | Article |
| id | doaj-art-91c18b0115d94059aa1753d37f043df4 |
| institution | DOAJ |
| issn | 2162-3279 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Brain and Behavior |
| spelling | doaj-art-91c18b0115d94059aa1753d37f043df42025-08-20T02:48:43ZengWileyBrain and Behavior2162-32792025-07-01157n/an/a10.1002/brb3.70644Acupuncture Alleviates Blood–Brain Barrier Damage After Delayed rtPA Thrombolysis for Acute Ischemic Stroke by Regulating FerroptosisZheng Huang0Tianliang Lu1Xinyu Liu2Zhihui Zhang3Yangyang Song4Yiyang Li5Wentao Xu6Xinchang Zhang7Guangxia Ni8College of Acupuncture‐Moxibustion and Tuina Nanjing University of Chinese Medicine Nanjing ChinaCollege of Acupuncture‐Moxibustion and Tuina Nanjing University of Chinese Medicine Nanjing ChinaCollege of Acupuncture‐Moxibustion and Tuina Nanjing University of Chinese Medicine Nanjing ChinaCollege of Acupuncture‐Moxibustion and Tuina Nanjing University of Chinese Medicine Nanjing ChinaCollege of Acupuncture‐Moxibustion and Tuina Nanjing University of Chinese Medicine Nanjing ChinaCollege of Acupuncture‐Moxibustion and Tuina Nanjing University of Chinese Medicine Nanjing ChinaCollege of Acupuncture‐Moxibustion and Tuina Nanjing University of Chinese Medicine Nanjing ChinaCollege of Acupuncture‐Moxibustion and Tuina Nanjing University of Chinese Medicine Nanjing ChinaCollege of Acupuncture‐Moxibustion and Tuina Nanjing University of Chinese Medicine Nanjing ChinaABSTRACT Background 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. Methods 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. Results 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. Conclusion 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.https://doi.org/10.1002/brb3.70644acupunctureacute ischemic strokeblood–brain barriercerebral infarctionferroptosisneuron |
| spellingShingle | Zheng Huang Tianliang Lu Xinyu Liu Zhihui Zhang Yangyang Song Yiyang Li Wentao Xu Xinchang Zhang Guangxia Ni Acupuncture Alleviates Blood–Brain Barrier Damage After Delayed rtPA Thrombolysis for Acute Ischemic Stroke by Regulating Ferroptosis Brain and Behavior acupuncture acute ischemic stroke blood–brain barrier cerebral infarction ferroptosis neuron |
| title | Acupuncture Alleviates Blood–Brain Barrier Damage After Delayed rtPA Thrombolysis for Acute Ischemic Stroke by Regulating Ferroptosis |
| title_full | Acupuncture Alleviates Blood–Brain Barrier Damage After Delayed rtPA Thrombolysis for Acute Ischemic Stroke by Regulating Ferroptosis |
| title_fullStr | Acupuncture Alleviates Blood–Brain Barrier Damage After Delayed rtPA Thrombolysis for Acute Ischemic Stroke by Regulating Ferroptosis |
| title_full_unstemmed | Acupuncture Alleviates Blood–Brain Barrier Damage After Delayed rtPA Thrombolysis for Acute Ischemic Stroke by Regulating Ferroptosis |
| title_short | Acupuncture Alleviates Blood–Brain Barrier Damage After Delayed rtPA Thrombolysis for Acute Ischemic Stroke by Regulating Ferroptosis |
| title_sort | acupuncture alleviates blood brain barrier damage after delayed rtpa thrombolysis for acute ischemic stroke by regulating ferroptosis |
| topic | acupuncture acute ischemic stroke blood–brain barrier cerebral infarction ferroptosis neuron |
| url | https://doi.org/10.1002/brb3.70644 |
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