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Hemorrhagic stroke-induced subtype of inflammatory reactive astrocytes disrupts blood-brain barrier.
Liu, Chang; Guo, Yiyan; Deng, Shiyu; Zhou, Shiyi; Wu, Shengju; Chen, Tingting; Shi, Xiaojing; Mamtilahun, Muyassar; Xu, Tongtong; Liu, Ze; Li, Hanlai; Zhang, Zhijun; Tian, Hengli; Chung, Won-Suk; Wang, Jixian; Yang, Guo-Yuan; Tang, Yaohui.
Afiliación
  • Liu C; Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
  • Guo Y; Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
  • Deng S; Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
  • Zhou S; Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
  • Wu S; Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
  • Chen T; Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
  • Shi X; Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
  • Mamtilahun M; Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
  • Xu T; Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
  • Liu Z; Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
  • Li H; Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
  • Zhang Z; Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
  • Tian H; Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
  • Chung WS; Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, South Korea.
  • Wang J; Department of Rehabilitation Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Yang GY; Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
  • Tang Y; Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
J Cereb Blood Flow Metab ; 44(7): 1102-1116, 2024 Jul.
Article en En | MEDLINE | ID: mdl-38388375
ABSTRACT
Astrocytes undergo disease-specific transcriptomic changes upon brain injury. However, phenotypic changes of astrocytes and their functions remain unclear after hemorrhagic stroke. Here we reported hemorrhagic stroke induced a group of inflammatory reactive astrocytes with high expression of Gfap and Vimentin, as well as inflammation-related genes lipocalin-2 (Lcn2), Complement component 3 (C3), and Serpina3n. In addition, we demonstrated that depletion of microglia but not macrophages inhibited the expression of inflammation-related genes in inflammatory reactive astrocytes. RNA sequencing showed that blood-brain barrier (BBB) disruption-related gene matrix metalloproteinase-3 (MMP3) was highly upregulated in inflammatory reactive astrocytes. Pharmacological inhibition of MMP3 in astrocytes or specific deletion of astrocytic MMP3 reduced BBB disruption and improved neurological outcomes of hemorrhagic stroke mice. Our study demonstrated that hemorrhagic stroke induced a group of inflammatory reactive astrocytes that were actively involved in disrupting BBB through MMP3, highlighting a specific group of inflammatory reactive astrocytes as a critical driver for BBB disruption in neurological diseases.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Barrera Hematoencefálica / Astrocitos / Metaloproteinasa 3 de la Matriz / Accidente Cerebrovascular Hemorrágico Límite: Animals Idioma: En Revista: J Cereb Blood Flow Metab Año: 2024 Tipo del documento: Article País de afiliación: China
Texto completo
Imprimir
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Barrera Hematoencefálica / Astrocitos / Metaloproteinasa 3 de la Matriz / Accidente Cerebrovascular Hemorrágico Límite: Animals Idioma: En Revista: J Cereb Blood Flow Metab Año: 2024 Tipo del documento: Article País de afiliación: China