PMID- 38388375
OWN - NLM
STAT- Publisher
LR  - 20240222
IS  - 1559-7016 (Electronic)
IS  - 0271-678X (Linking)
DP  - 2024 Feb 22
TI  - Hemorrhagic stroke-induced subtype of inflammatory reactive astrocytes disrupts 
      blood-brain barrier.
PG  - 271678X241235008
LID - 10.1177/0271678X241235008 [doi]
AB  - 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.
FAU - Liu, Chang
AU  - Liu C
AD  - Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of 
      Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China. RINGGOLD: 
      12474
FAU - Guo, Yiyan
AU  - Guo Y
AD  - Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of 
      Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China. RINGGOLD: 
      12474
FAU - Deng, Shiyu
AU  - Deng S
AD  - Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of 
      Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China. RINGGOLD: 
      12474
FAU - Zhou, Shiyi
AU  - Zhou S
AD  - Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of 
      Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China. RINGGOLD: 
      12474
FAU - Wu, Shengju
AU  - Wu S
AD  - Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of 
      Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China. RINGGOLD: 
      12474
FAU - Chen, Tingting
AU  - Chen T
AD  - Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of 
      Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China. RINGGOLD: 
      12474
FAU - Shi, Xiaojing
AU  - Shi X
AD  - Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of 
      Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China. RINGGOLD: 
      12474
FAU - Mamtilahun, Muyassar
AU  - Mamtilahun M
AD  - Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of 
      Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China. RINGGOLD: 
      12474
FAU - Xu, Tongtong
AU  - Xu T
AD  - Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of 
      Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China. RINGGOLD: 
      12474
FAU - Liu, Ze
AU  - Liu Z
AD  - Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of 
      Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China. RINGGOLD: 
      12474
FAU - Li, Hanlai
AU  - Li H
AD  - Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of 
      Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China. RINGGOLD: 
      12474
FAU - Zhang, Zhijun
AU  - Zhang Z
AD  - Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of 
      Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China. RINGGOLD: 
      12474
FAU - Tian, Hengli
AU  - Tian H
AD  - Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of 
      Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China. RINGGOLD: 
      12474
FAU - Chung, Won-Suk
AU  - Chung WS
AD  - Department of Biological Sciences, Korea Advanced Institute of Science and 
      Technology, Daejeon, South Korea. RINGGOLD: 34968
FAU - Wang, Jixian
AU  - Wang J
AD  - Department of Rehabilitation Medicine, Ruijin Hospital, School of Medicine, 
      Shanghai Jiao Tong University, Shanghai, China.
FAU - Yang, Guo-Yuan
AU  - Yang GY
AD  - Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of 
      Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China. RINGGOLD: 
      12474
FAU - Tang, Yaohui
AU  - Tang Y
AUID- ORCID: 0000-0002-9603-2650
AD  - Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of 
      Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China. RINGGOLD: 
      12474
LA  - eng
PT  - Journal Article
DEP - 20240222
PL  - United States
TA  - J Cereb Blood Flow Metab
JT  - Journal of cerebral blood flow and metabolism : official journal of the 
      International Society of Cerebral Blood Flow and Metabolism
JID - 8112566
SB  - IM
OTO - NOTNLM
OT  - Single-cell RNA sequencing
OT  - blood-brain barrier
OT  - hemorrhagic stroke
OT  - matrix metalloproteinase-3
OT  - reactive astrocytes
COIS- Declaration of conflicting interestsThe author(s) declared no potential conflicts 
      of interest with respect to the research, authorship, and/or publication of this 
      article.
EDAT- 2024/02/23 00:42
MHDA- 2024/02/23 00:42
CRDT- 2024/02/22 23:33
PHST- 2024/02/23 00:42 [medline]
PHST- 2024/02/23 00:42 [pubmed]
PHST- 2024/02/22 23:33 [entrez]
AID - 10.1177/0271678X241235008 [doi]
PST - aheadofprint
SO  - J Cereb Blood Flow Metab. 2024 Feb 22:271678X241235008. doi: 
      10.1177/0271678X241235008.