Electroacupuncture suppresses NK cell infiltration and activation in the ischemic mouse brain through STAT3 inhibition

ABSTRACT: Aims: Electroacupuncture (EA) at Shuigou (GV26) and Baihui (GV20) has shown therapeutic benefits for stroke patients. Given that natural killer (NK) cell infiltration into the brain significantly contributes to the exacerbation of cerebral ischemic injury, this study investigated the impa...

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Main Authors: Ao Xu, Ziqing Li, Yangyang Ding, Xiaoyu Wang, Yufang Yang, Lixia Du, Deheng Wang, Shi Shu, Zhifei Wang
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Brain Research Bulletin
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Online Access:http://www.sciencedirect.com/science/article/pii/S0361923024002624
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author Ao Xu
Ziqing Li
Yangyang Ding
Xiaoyu Wang
Yufang Yang
Lixia Du
Deheng Wang
Shi Shu
Zhifei Wang
author_facet Ao Xu
Ziqing Li
Yangyang Ding
Xiaoyu Wang
Yufang Yang
Lixia Du
Deheng Wang
Shi Shu
Zhifei Wang
author_sort Ao Xu
collection DOAJ
description ABSTRACT: Aims: Electroacupuncture (EA) at Shuigou (GV26) and Baihui (GV20) has shown therapeutic benefits for stroke patients. Given that natural killer (NK) cell infiltration into the brain significantly contributes to the exacerbation of cerebral ischemic injury, this study investigated the impact of EA at Shuigou (GV26) and Baihui (GV20) on post-ischemic brain infiltration and activation of NK cells. Methods: Neurological deficit score, rotarod test, adhesive removal test, and TTC staining were used to evaluate the beneficial effects of EA in middle cerebral artery occlusion (MCAO) mice. The inhibitory effect of EA on STAT3 activation was assessed using Western blot. Flow cytometry was used to explore the impact of EA on post-ischemic brain infiltration of NK cells, as well as the activating receptor NKG2D expression and interferon-γ (IFN-γ) production by these infiltrated NK cells. Results: EA significantly alleviated neurological functional deficits and reduced brain infarction in MCAO mice. Abundant NK cells infiltrated into the ischemic hemisphere, but this infiltration was significantly suppressed by EA. Furthermore, EA attenuated NKG2D levels and reduced production of IFN-γ by NK cells in the ischemic brain. Notably, EA's inhibitory effect on post-ischemic NK cell brain infiltration and activation was comparable to that of STAT3 inhibition. The combination of EA and STAT3 inhibition did not result in further enhancement of the inhibitory effect. Moreover, the protective effects of EA against MCAO injury were abolished when STAT3 was activated. Conclusion: Our findings suggest that EA at Shuigou (GV26) and Baihui (GV20) inhibits the post-ischemic brain infiltration and activation of NK cells through STAT3 inhibition, significantly contributing to its therapeutic effects against brain ischemia.
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issn 1873-2747
language English
publishDate 2024-12-01
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series Brain Research Bulletin
spelling doaj-art-f5382056bb724d50a4a606f7929a57d32024-11-28T04:34:06ZengElsevierBrain Research Bulletin1873-27472024-12-01219111128Electroacupuncture suppresses NK cell infiltration and activation in the ischemic mouse brain through STAT3 inhibitionAo Xu0Ziqing Li1Yangyang Ding2Xiaoyu Wang3Yufang Yang4Lixia Du5Deheng Wang6Shi Shu7Zhifei Wang8School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaSchool of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Acupuncture and Moxibustion Department, Nanchang Hongdu Hospital of Traditional Chinese Medicine, Nanchang, Jiangxi 330008, ChinaSchool of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaSchool of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaSchool of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaSchool of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaSchool of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaSchool of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Corresponding authors.School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Corresponding authors.ABSTRACT: Aims: Electroacupuncture (EA) at Shuigou (GV26) and Baihui (GV20) has shown therapeutic benefits for stroke patients. Given that natural killer (NK) cell infiltration into the brain significantly contributes to the exacerbation of cerebral ischemic injury, this study investigated the impact of EA at Shuigou (GV26) and Baihui (GV20) on post-ischemic brain infiltration and activation of NK cells. Methods: Neurological deficit score, rotarod test, adhesive removal test, and TTC staining were used to evaluate the beneficial effects of EA in middle cerebral artery occlusion (MCAO) mice. The inhibitory effect of EA on STAT3 activation was assessed using Western blot. Flow cytometry was used to explore the impact of EA on post-ischemic brain infiltration of NK cells, as well as the activating receptor NKG2D expression and interferon-γ (IFN-γ) production by these infiltrated NK cells. Results: EA significantly alleviated neurological functional deficits and reduced brain infarction in MCAO mice. Abundant NK cells infiltrated into the ischemic hemisphere, but this infiltration was significantly suppressed by EA. Furthermore, EA attenuated NKG2D levels and reduced production of IFN-γ by NK cells in the ischemic brain. Notably, EA's inhibitory effect on post-ischemic NK cell brain infiltration and activation was comparable to that of STAT3 inhibition. The combination of EA and STAT3 inhibition did not result in further enhancement of the inhibitory effect. Moreover, the protective effects of EA against MCAO injury were abolished when STAT3 was activated. Conclusion: Our findings suggest that EA at Shuigou (GV26) and Baihui (GV20) inhibits the post-ischemic brain infiltration and activation of NK cells through STAT3 inhibition, significantly contributing to its therapeutic effects against brain ischemia.http://www.sciencedirect.com/science/article/pii/S0361923024002624ElectroacupunctureShuigou (GV26)Baihui (GV20)Ischemic strokeNatural killer cellsSignal transducer and activator of transcription 3
spellingShingle Ao Xu
Ziqing Li
Yangyang Ding
Xiaoyu Wang
Yufang Yang
Lixia Du
Deheng Wang
Shi Shu
Zhifei Wang
Electroacupuncture suppresses NK cell infiltration and activation in the ischemic mouse brain through STAT3 inhibition
Brain Research Bulletin
Electroacupuncture
Shuigou (GV26)
Baihui (GV20)
Ischemic stroke
Natural killer cells
Signal transducer and activator of transcription 3
title Electroacupuncture suppresses NK cell infiltration and activation in the ischemic mouse brain through STAT3 inhibition
title_full Electroacupuncture suppresses NK cell infiltration and activation in the ischemic mouse brain through STAT3 inhibition
title_fullStr Electroacupuncture suppresses NK cell infiltration and activation in the ischemic mouse brain through STAT3 inhibition
title_full_unstemmed Electroacupuncture suppresses NK cell infiltration and activation in the ischemic mouse brain through STAT3 inhibition
title_short Electroacupuncture suppresses NK cell infiltration and activation in the ischemic mouse brain through STAT3 inhibition
title_sort electroacupuncture suppresses nk cell infiltration and activation in the ischemic mouse brain through stat3 inhibition
topic Electroacupuncture
Shuigou (GV26)
Baihui (GV20)
Ischemic stroke
Natural killer cells
Signal transducer and activator of transcription 3
url http://www.sciencedirect.com/science/article/pii/S0361923024002624
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