2. Academic Validation
  3. An integral blood-brain barrier in adulthood relies on microglia-derived PDGFB

An integral blood-brain barrier in adulthood relies on microglia-derived PDGFB

  • Brain Behav Immun. 2024 Jan:115:705-717. doi: 10.1016/j.bbi.2023.11.023.
Yuancheng Weng 1,  Ningting Chen 2,  Rui Zhang 3,  Jian He 4,  Xukai Ding 1,  Guo Cheng 2,  Qianqian Bi 5,  Ying-Mei Lu 6,  Xiao Z Shen 7,  Shu Wan 8,  Peng Shi 9
Affiliations

Affiliations

  • 1 Department of Physiology and Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • 2 Department of Cardiology of the Second Affiliated Hospital, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • 3 Brain Center, Affiliated Zhejiang Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
  • 4 Brain Center, Affiliated Zhejiang Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • 5 The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
  • 6 Department of Physiology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China.
  • 7 Department of Physiology and Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Brain Center, Affiliated Zhejiang Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. Electronic address: [email protected].
  • 8 Brain Center, Affiliated Zhejiang Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China. Electronic address: [email protected].
  • 9 Department of Cardiology of the Second Affiliated Hospital, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. Electronic address: [email protected].
PMID: 37992789 DOI: 10.1016/j.bbi.2023.11.023
Abstract

Pericyte is an indispensable cellular constituent of blood-brain barrier (BBB) and its homeostasis heavily rely on PDGFB-PDGFRβ signaling. However, the primary cellular sources of PDGFB in the central nervous system (CNS) are unclear. Microglia is not considered a component of BBB and its role in maintaining BBB integrity in steady state is controversial. In this study, by analyzing transcriptomic data and performing in situ hybridization, we revealed a transition of the primary central PDGFB producers from endothelial cells in newborns to microglia in adults. Acute loss of microglial PDGFB profoundly impaired BBB integrity in adult but not newborn mice, and thus, adult mice deficient of microglial PDGFB could not survive from a sublethal endotoxin challenge due to rampant microhemorrhages in the CNS. In contrast, acute abrogation of endothelial PDGFB had minimal effects on the BBB of adult mice but led to a severe impairment of CNS vasculature in the neonates. Moreover, we found that microglia would respond to a variety of BBB insults by upregulating PDGFB expression. These findings underscore the physiological importance of the microglia-derived PDGFB to the BBB integrity of adult mice both in steady state and under injury.

Keywords

Blood–brain barrier; Microglia; PDGFB; Pericytes.

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