z-logo
Premium
Platelet regulates neuroinflammation and restores blood–brain barrier integrity in a mouse model of traumatic brain injury
Author(s) -
Gao Cheng,
Wang Haochen,
Wang Tao,
Luo Chengliang,
Wang Zufeng,
Zhang Mingyang,
Chen Xiping,
Tao Luyang
Publication year - 2020
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14983
Subject(s) - neuroinflammation , microglia , traumatic brain injury , inflammation , platelet , proinflammatory cytokine , platelet activation , medicine , immunology , psychiatry
Neuroinflammation accompanied by microglial activation triggers multiple cell death after traumatic brain injury (TBI). The secondary injury caused by inflammation may persist for a long time. Recently, platelet C‐type lectin‐like 2 receptor (CLEC‐2) has been shown to regulate inflammation in certain diseases. However, its possible effects on TBI remain poorly understood. Here, we aimed to investigate the role of platelet CLEC‐2 in the pathological process of neuroinflammation after TBI. In this study, mice were subjected to sham or controlled cortical impact injury, and arbitrarily received recombinant platelet CLEC‐2. In parallel, BV2 cells were treated with lipopolysaccharide (LPS) to mimic microglial activation after TBI. Primary endothelial cells were also subjected to LPS in order to replicate the inflammatory damage caused by TBI. We used western blot analysis, reverse transcription polymerase chain reaction (RT‐PCR), and immunostaining to evaluate the role of platelet CLEC‐2 in TBI. In conditional knock out platelet CLEC‐2 mice, trauma worsened the integrity of the blood–brain barrier and amplified the release of inflammatory cytokines. In wild type mice subjected to controlled cortical impact injury, recombinant platelet CLEC‐2 administration altered the secretion of inflammatory cytokines, reduced brain edema, and improved neurological function. In vitro, the polarization phenotype of microglia induced by LPS was transformed by recombinant platelet CLEC‐2, and this conversion depended on the mammalian target of rapamycin (mTOR) pathway. Endothelial cell injury by LPS was ameliorated when microglia expressed mostly M2 phenotype markers. In conclusion, platelet CLEC‐2 regulates trauma‐induced neuroinflammation and restores blood–brain barrier integrity.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here