• Neuroscience · May 2019

    Inhibition of TREM-1 attenuates early brain injury after subarachnoid hemorrhage via downregulation of p38MAPK/MMP-9 and preservation of ZO-1.

    • Xin-Gang Sun, Hongling Duan, Gang Jing, Gaiqing Wang, Yazhi Hou, and Mimi Zhang.
    • Department of Neurology, the Second Hospital Affiliated to Shanxi Medical University, 382 Wuyi Road, Taiyuan, Shanxi 030000, China. Electronic address: sunyanxia820701@163.com.
    • Neuroscience. 2019 May 15; 406: 369-375.

    AbstractEarly brain injury (EBI) mainly leads to the poor outcome of subarachnoid hemorrhage (SAH), with which inflammation is closely associated. It was reported that triggering receptor expressed on myeloid cells-1 (TREM-1), a critical inflammatory amplifier, increased in cerebrospinal fluid of SAH patients in our recent research. This study was conducted to examine the effects of TREM-1 inhibition on EBI after experimental SAH (eSAH). The endovascular perforation model of SAH was produced and 120 rats were randomly divided into four groups as sham, SAH + vehicle and SAH + LP17 (1.0 mg/kg and 3.5 mg/kg). The LP17, a selective inhibitor of TREM-1, or vehicle was administered by an intraperitoneal injection 1 h post-modeling. Western blot analysis for TREM-1, p38 mitogen-activated protein kinase (p38MAPK), matrix metalloproteinase-9 (MMP-9) and zonula occludens-1 (ZO-1) was conducted at 24 h post-modeling. EBI was assessed in terms of mortality, neuroscore, brain edema, blood-brain barrier (BBB) disruption in 24 and 72 h. The results showed that TREM-1 was induced in brain after eSAH. Both high dose (3.5 mg/kg) and low dose (1.0 mg/kg) of Lp17 significantly inhibited the induction of TREM-1, but only high dose of LP17 improved neuroscore, brain edema, and BBB disruption which are associated with downregulation of p38MAPK/MMP-9 and subsequent preservation of ZO-1. Overall, the current study provides new evidence that TREM-1 may participate in the pathogenesis of SAH-induced EBI via promoting p38MAPK/MMP-9 activation and ZO-1 degradation, while TREM-1 inhibition attenuated the EBI severity obviously, providing a novel approach for the treatment of EBI.Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.

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