Carotid Endarterectomy Ameliorates Cognitive Impairment in Clinical and Experimental Unilateral Carotid Artery Stenosis

Background Carotid endarterectomy (CEA) is widely used to treat carotid artery stenosis (CAS). However, the effects of CEA on unilateral CAS‐induced cognitive impairment and the underlying mechanism remain poorly understood. Methods and Results Thirteen patients diagnosed with unilateral severe CAS...

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Main Authors: Yijun Cheng, Bin Chen, Miao Zhang, Zhenghong Chen, Mingjian Liu, Ziqian Zhang, Hao Tang, Dapeng Wang, Wenwen Lv, Biao Li, Yuting Dai, Hanbing Shang
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
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Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.124.038388
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author Yijun Cheng
Bin Chen
Miao Zhang
Zhenghong Chen
Mingjian Liu
Ziqian Zhang
Hao Tang
Dapeng Wang
Wenwen Lv
Biao Li
Yuting Dai
Hanbing Shang
author_facet Yijun Cheng
Bin Chen
Miao Zhang
Zhenghong Chen
Mingjian Liu
Ziqian Zhang
Hao Tang
Dapeng Wang
Wenwen Lv
Biao Li
Yuting Dai
Hanbing Shang
author_sort Yijun Cheng
collection DOAJ
description Background Carotid endarterectomy (CEA) is widely used to treat carotid artery stenosis (CAS). However, the effects of CEA on unilateral CAS‐induced cognitive impairment and the underlying mechanism remain poorly understood. Methods and Results Thirteen patients diagnosed with unilateral severe CAS underwent pre‐ and post‐CEA assessments, including 18fluoro‐2‐deoxy‐d‐glucose positron emission tomography/magnetic resonance imaging, cognitive assessments, and routine blood tests before and after CEA. Unilateral carotid common artery occlusion and ligation release (reperfusion) surgeries were performed in mice to mimic CAS and CEA. Cognitive function, cerebral blood flow, and white matter damage were evaluated in mice using the Morris water maze test, Doppler flowmetry, laser‐speckle imaging, diffusion tensor imaging, Luxol fast blue staining, transmission electron microscopy, and western blot assays post unilateral carotid common artery occlusion and reperfusion. Genomic sequencing of the white matter was performed to explore the potential underlying mechanism. CEA significantly enhanced the Montreal Cognitive Assessment scores in patients with CAS and preoperative cognitive impairment. Moreover, CEA led to notable improvements in cerebral blood flow, energy metabolism, and white matter integrity, while concurrently reducing blood inflammation. In the mouse model, reperfusion surgery alleviated cognitive deficits, increased cerebral blood flow, and alleviated white matter damage following unilateral carotid common artery occlusion. Furthermore, transcriptional surveys have revealed substantial alterations in the upregulation of Nrf2 signaling and metabolic pathways, coupled with the inhibition of neuroinflammation, cellular communication, and immune cell population signaling following reperfusion. Conclusions CEA ameliorated CAS‐induced cognitive dysfunction by improving the cerebral functional structure. These beneficial effects may be attributed to their antioxidant and anti‐inflammatory properties.
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spelling doaj-art-05e3d02b2c2f4e9396710bc4a7adad752025-08-20T03:24:52ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802025-01-0114210.1161/JAHA.124.038388Carotid Endarterectomy Ameliorates Cognitive Impairment in Clinical and Experimental Unilateral Carotid Artery StenosisYijun Cheng0Bin Chen1Miao Zhang2Zhenghong Chen3Mingjian Liu4Ziqian Zhang5Hao Tang6Dapeng Wang7Wenwen Lv8Biao Li9Yuting Dai10Hanbing Shang11Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Neurosurgery, Ruijin Hospital Luwan Branch Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Nuclear Medicine, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Neurosurgery, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Neurosurgery, Huashan Hospital, Shanghai Medical College Fudan University Shanghai ChinaDepartment of Neurosurgery, Xuanwu Hospital Capital Medical University Beijing ChinaDepartment of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai ChinaClinical Research Center, School of Medicine Shanghai Jiao Tong University Shanghai ChinaDepartment of Nuclear Medicine, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai ChinaShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai ChinaBackground Carotid endarterectomy (CEA) is widely used to treat carotid artery stenosis (CAS). However, the effects of CEA on unilateral CAS‐induced cognitive impairment and the underlying mechanism remain poorly understood. Methods and Results Thirteen patients diagnosed with unilateral severe CAS underwent pre‐ and post‐CEA assessments, including 18fluoro‐2‐deoxy‐d‐glucose positron emission tomography/magnetic resonance imaging, cognitive assessments, and routine blood tests before and after CEA. Unilateral carotid common artery occlusion and ligation release (reperfusion) surgeries were performed in mice to mimic CAS and CEA. Cognitive function, cerebral blood flow, and white matter damage were evaluated in mice using the Morris water maze test, Doppler flowmetry, laser‐speckle imaging, diffusion tensor imaging, Luxol fast blue staining, transmission electron microscopy, and western blot assays post unilateral carotid common artery occlusion and reperfusion. Genomic sequencing of the white matter was performed to explore the potential underlying mechanism. CEA significantly enhanced the Montreal Cognitive Assessment scores in patients with CAS and preoperative cognitive impairment. Moreover, CEA led to notable improvements in cerebral blood flow, energy metabolism, and white matter integrity, while concurrently reducing blood inflammation. In the mouse model, reperfusion surgery alleviated cognitive deficits, increased cerebral blood flow, and alleviated white matter damage following unilateral carotid common artery occlusion. Furthermore, transcriptional surveys have revealed substantial alterations in the upregulation of Nrf2 signaling and metabolic pathways, coupled with the inhibition of neuroinflammation, cellular communication, and immune cell population signaling following reperfusion. Conclusions CEA ameliorated CAS‐induced cognitive dysfunction by improving the cerebral functional structure. These beneficial effects may be attributed to their antioxidant and anti‐inflammatory properties.https://www.ahajournals.org/doi/10.1161/JAHA.124.038388carotid artery stenosiscarotid endarterectomycognitive impairmentgenomic sequencingPET/MRwhite blood cell
spellingShingle Yijun Cheng
Bin Chen
Miao Zhang
Zhenghong Chen
Mingjian Liu
Ziqian Zhang
Hao Tang
Dapeng Wang
Wenwen Lv
Biao Li
Yuting Dai
Hanbing Shang
Carotid Endarterectomy Ameliorates Cognitive Impairment in Clinical and Experimental Unilateral Carotid Artery Stenosis
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
carotid artery stenosis
carotid endarterectomy
cognitive impairment
genomic sequencing
PET/MR
white blood cell
title Carotid Endarterectomy Ameliorates Cognitive Impairment in Clinical and Experimental Unilateral Carotid Artery Stenosis
title_full Carotid Endarterectomy Ameliorates Cognitive Impairment in Clinical and Experimental Unilateral Carotid Artery Stenosis
title_fullStr Carotid Endarterectomy Ameliorates Cognitive Impairment in Clinical and Experimental Unilateral Carotid Artery Stenosis
title_full_unstemmed Carotid Endarterectomy Ameliorates Cognitive Impairment in Clinical and Experimental Unilateral Carotid Artery Stenosis
title_short Carotid Endarterectomy Ameliorates Cognitive Impairment in Clinical and Experimental Unilateral Carotid Artery Stenosis
title_sort carotid endarterectomy ameliorates cognitive impairment in clinical and experimental unilateral carotid artery stenosis
topic carotid artery stenosis
carotid endarterectomy
cognitive impairment
genomic sequencing
PET/MR
white blood cell
url https://www.ahajournals.org/doi/10.1161/JAHA.124.038388
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