Role of TREM-1 in the development of early brain injury after subarachnoid hemorrhage. |
| Authors: |
Sun, Xin-Gang Zhang, Mi-Mi Liu, Shao-Yu Chu, Xue-Hong Xue, Guo-Qiang Zhang, Bao-Chen Zhu, Jia-Bao Godje Godje, Ivan Steve Zhu, Li-Juan Hu, Hui-Yu Hai-Wang, Shen, Ying-Jie Wang, Gai-Qing
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| Citation: |
Sun XG, etal., Exp Neurol. 2021 Jul;341:113692. doi: 10.1016/j.expneurol.2021.113692. Epub 2021 Mar 13. |
| RGD ID: |
127284864 |
| Pubmed: |
PMID:33727099 (View Abstract at PubMed) |
| DOI: |
DOI:10.1016/j.expneurol.2021.113692 (Journal Full-text) |
Triggering receptor expressed on myeloid cells-1 (TREM-1) was found to be induced in the context of subarachnoid hemorrhage (SAH) before. This study further investigates its role in the development of SAH-induced early brain injury (EBI). Firstly, rats were randomly divided into Sham and SAH groups for analysis of temporal patterns and cellular localization of TREM-1. Secondly, TREM-1 intervention was administrated to produce Sham, vehicle, antagonist and agonist groups, for analyzing TREM-1, Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and NF-κB expressions at 24 h post-modeling, and EBI assessment at 24 h and 72 h. Thirdly, TLR4 inhibitor (TAK-242) was exploited to produce Sham, Sham+TAK-242, SAH, and SAH + TAK-242 groups to analyze the effects of TLR4 inhibition on TREM-1 induction and EBI evaluation at 72 h. Fourthly, the relationship of soluble TREM-1 (sTREM-1) levels in cerebrospinal fluid of SAH patients with Hunt-Hess grades were explored. The results showed that TREM-1 increased in the brain after experimental SAH (eSAH) early at 6 h and peaked at 48 h, which was found to be located in microglia and endothelial cells. TREM-1 inhibition attenuated EBI associated with TLR4/MyD88/NF-κB suppression, while enhancement had the opposite effects. Contrarily, TLR4 inhibition prevented TREM-1 induction and ameliorated EBI. In addition, sTREM-1 levels in SAH patients positively correlated with Hunt-Hess grades. Overall, the present study provides new evidence that TREM-1 increases dynamically in the brain after eSAH and it is located in microglia and endothelial cells, which may aggravate EBI by interacting with TLR4 pathway. And sTREM-1 in patients might act as a monitoring biomarker of EBI, providing new insights for future studies.
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| Genes (Rattus norvegicus) |
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| Trem1 (triggering receptor expressed on myeloid cells 1) |
| Genes (Mus musculus) |
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| Trem1 (triggering receptor expressed on myeloid cells 1) |
| Genes (Homo sapiens) |
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| TREM1 (triggering receptor expressed on myeloid cells 1) |
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