SARM1 deletion inhibits astrogliosis and BBB damage through Jagged-1/Notch-1/NF-κB signaling to improve neurological function after ischemic stroke
Reactive astrogliosis is a critical process in the development of ischemic stroke. However, the precise mechanism by which reactive astrogliosis changes the pathogenesis of ischemic stroke remains elusive. Sterile alpha and TIR motif-containing 1 protein (SARM1) plays a key role in axonal degenerati...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-05-01
|
| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996125000890 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850186265268322304 |
|---|---|
| author | Yan Qiong Fu Yu Zheng Zhuo Li Li Xin Yi Huang Xiao Wan Wang Mai Yin Cui Yun Qi Zhang Bing Rui Gao Chan Zhang Xiao Xiao Fan Yong Jian Bai Hui Chen |
| author_facet | Yan Qiong Fu Yu Zheng Zhuo Li Li Xin Yi Huang Xiao Wan Wang Mai Yin Cui Yun Qi Zhang Bing Rui Gao Chan Zhang Xiao Xiao Fan Yong Jian Bai Hui Chen |
| author_sort | Yan Qiong Fu |
| collection | DOAJ |
| description | Reactive astrogliosis is a critical process in the development of ischemic stroke. However, the precise mechanism by which reactive astrogliosis changes the pathogenesis of ischemic stroke remains elusive. Sterile alpha and TIR motif-containing 1 protein (SARM1) plays a key role in axonal degeneration and is involved in different cell death programs that regulate neuronal survival. The present study investigated the role of SARM1 in regulating reactive astrogliosis and neurological function after stroke in whole-body SARM1 knockout (SARM1−/−) mice. SARM1−/− mice showed significantly smaller infarction, slighter apoptosis, and fewer neurological function deficits 1–7 days after ischemic injury. Immunohistochemistry, western blot, and real-time PCR analyses revealed that compared with the wild-type (WT) mice, SARM1−/− mice exhibited reduced astrocytic proliferation, increased anti-inflammatory astrocytes, decreased glial scar formation in the infarct zone on day 7 after ischemic injury. SARM1 deletion also suppressed cerebral microvascular damage and blood-brain barrier (BBB) injury in ischemic brains. Mechanistically, SARM1 deletion inhibited the stroke-triggered activation of NF-κB signaling and decreased the expression of Jagged-1 and NICD in astrocytes. Overall, these findings provide the first line of evidence for a causative role of SARM1 protein in ischemia-induced reactive astrogliosis and ischemic neurovascular damage. |
| format | Article |
| id | doaj-art-842422cfe7f144cc97f5e781cdcb4e25 |
| institution | OA Journals |
| issn | 1095-953X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj-art-842422cfe7f144cc97f5e781cdcb4e252025-08-20T02:16:27ZengElsevierNeurobiology of Disease1095-953X2025-05-0120810687310.1016/j.nbd.2025.106873SARM1 deletion inhibits astrogliosis and BBB damage through Jagged-1/Notch-1/NF-κB signaling to improve neurological function after ischemic strokeYan Qiong Fu0Yu Zheng1Zhuo Li Li2Xin Yi Huang3Xiao Wan Wang4Mai Yin Cui5Yun Qi Zhang6Bing Rui Gao7Chan Zhang8Xiao Xiao Fan9Yong Jian10Bai Hui Chen11Department of Histology and Embryology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, PR ChinaDepartment of Histology and Embryology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, PR ChinaDepartment of Histology and Embryology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, PR ChinaDepartment of Histology and Embryology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, PR ChinaDepartment of Histology and Embryology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, PR ChinaDepartment of Rehabilitation and Traditional Chinese Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310052, Zhejiang, PR ChinaDepartment of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, PR ChinaDepartment of Endocrinology and Metabolism, The Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Disease, The First Hospital of China Medical University, Shenyang 110000, Liaoning, PR ChinaSchool of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, PR ChinaDepartment of Histology and Embryology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, PR China; Correspondence to: X X. Fan; B H. Chen; Department of Histology and Embryology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, PR China.Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325001, Zhejiang, PR China; Correspondence to: Y. Jian; Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325001, PR China.Department of Histology and Embryology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, PR China; Correspondence to: X X. Fan; B H. Chen; Department of Histology and Embryology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, PR China.Reactive astrogliosis is a critical process in the development of ischemic stroke. However, the precise mechanism by which reactive astrogliosis changes the pathogenesis of ischemic stroke remains elusive. Sterile alpha and TIR motif-containing 1 protein (SARM1) plays a key role in axonal degeneration and is involved in different cell death programs that regulate neuronal survival. The present study investigated the role of SARM1 in regulating reactive astrogliosis and neurological function after stroke in whole-body SARM1 knockout (SARM1−/−) mice. SARM1−/− mice showed significantly smaller infarction, slighter apoptosis, and fewer neurological function deficits 1–7 days after ischemic injury. Immunohistochemistry, western blot, and real-time PCR analyses revealed that compared with the wild-type (WT) mice, SARM1−/− mice exhibited reduced astrocytic proliferation, increased anti-inflammatory astrocytes, decreased glial scar formation in the infarct zone on day 7 after ischemic injury. SARM1 deletion also suppressed cerebral microvascular damage and blood-brain barrier (BBB) injury in ischemic brains. Mechanistically, SARM1 deletion inhibited the stroke-triggered activation of NF-κB signaling and decreased the expression of Jagged-1 and NICD in astrocytes. Overall, these findings provide the first line of evidence for a causative role of SARM1 protein in ischemia-induced reactive astrogliosis and ischemic neurovascular damage.http://www.sciencedirect.com/science/article/pii/S0969996125000890SARM1Ischemic strokeAstrogliosisNeuroinflammationJagged-1Notch-1 |
| spellingShingle | Yan Qiong Fu Yu Zheng Zhuo Li Li Xin Yi Huang Xiao Wan Wang Mai Yin Cui Yun Qi Zhang Bing Rui Gao Chan Zhang Xiao Xiao Fan Yong Jian Bai Hui Chen SARM1 deletion inhibits astrogliosis and BBB damage through Jagged-1/Notch-1/NF-κB signaling to improve neurological function after ischemic stroke Neurobiology of Disease SARM1 Ischemic stroke Astrogliosis Neuroinflammation Jagged-1 Notch-1 |
| title | SARM1 deletion inhibits astrogliosis and BBB damage through Jagged-1/Notch-1/NF-κB signaling to improve neurological function after ischemic stroke |
| title_full | SARM1 deletion inhibits astrogliosis and BBB damage through Jagged-1/Notch-1/NF-κB signaling to improve neurological function after ischemic stroke |
| title_fullStr | SARM1 deletion inhibits astrogliosis and BBB damage through Jagged-1/Notch-1/NF-κB signaling to improve neurological function after ischemic stroke |
| title_full_unstemmed | SARM1 deletion inhibits astrogliosis and BBB damage through Jagged-1/Notch-1/NF-κB signaling to improve neurological function after ischemic stroke |
| title_short | SARM1 deletion inhibits astrogliosis and BBB damage through Jagged-1/Notch-1/NF-κB signaling to improve neurological function after ischemic stroke |
| title_sort | sarm1 deletion inhibits astrogliosis and bbb damage through jagged 1 notch 1 nf κb signaling to improve neurological function after ischemic stroke |
| topic | SARM1 Ischemic stroke Astrogliosis Neuroinflammation Jagged-1 Notch-1 |
| url | http://www.sciencedirect.com/science/article/pii/S0969996125000890 |
| work_keys_str_mv | AT yanqiongfu sarm1deletioninhibitsastrogliosisandbbbdamagethroughjagged1notch1nfkbsignalingtoimproveneurologicalfunctionafterischemicstroke AT yuzheng sarm1deletioninhibitsastrogliosisandbbbdamagethroughjagged1notch1nfkbsignalingtoimproveneurologicalfunctionafterischemicstroke AT zhuolili sarm1deletioninhibitsastrogliosisandbbbdamagethroughjagged1notch1nfkbsignalingtoimproveneurologicalfunctionafterischemicstroke AT xinyihuang sarm1deletioninhibitsastrogliosisandbbbdamagethroughjagged1notch1nfkbsignalingtoimproveneurologicalfunctionafterischemicstroke AT xiaowanwang sarm1deletioninhibitsastrogliosisandbbbdamagethroughjagged1notch1nfkbsignalingtoimproveneurologicalfunctionafterischemicstroke AT maiyincui sarm1deletioninhibitsastrogliosisandbbbdamagethroughjagged1notch1nfkbsignalingtoimproveneurologicalfunctionafterischemicstroke AT yunqizhang sarm1deletioninhibitsastrogliosisandbbbdamagethroughjagged1notch1nfkbsignalingtoimproveneurologicalfunctionafterischemicstroke AT bingruigao sarm1deletioninhibitsastrogliosisandbbbdamagethroughjagged1notch1nfkbsignalingtoimproveneurologicalfunctionafterischemicstroke AT chanzhang sarm1deletioninhibitsastrogliosisandbbbdamagethroughjagged1notch1nfkbsignalingtoimproveneurologicalfunctionafterischemicstroke AT xiaoxiaofan sarm1deletioninhibitsastrogliosisandbbbdamagethroughjagged1notch1nfkbsignalingtoimproveneurologicalfunctionafterischemicstroke AT yongjian sarm1deletioninhibitsastrogliosisandbbbdamagethroughjagged1notch1nfkbsignalingtoimproveneurologicalfunctionafterischemicstroke AT baihuichen sarm1deletioninhibitsastrogliosisandbbbdamagethroughjagged1notch1nfkbsignalingtoimproveneurologicalfunctionafterischemicstroke |