Inhibition of TREM-1 attenuates early brain injury after subarachnoid hemorrhage via downregulation of p38MAPK/MMP-9 and preservation of ZO-1
| Autor: | Mi-Mi Zhang, Yazhi Hou, Gaiqing Wang, Gang Jing, Xin-gang Sun, Hongling Duan |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Subarachnoid hemorrhage medicine.medical_treatment p38 mitogen-activated protein kinases Intraperitoneal injection Perforation (oil well) Down-Regulation Inflammation Pharmacology p38 Mitogen-Activated Protein Kinases Tight Junctions Pathogenesis Rats Sprague-Dawley 03 medical and health sciences Random Allocation 0302 clinical medicine Cerebrospinal fluid Downregulation and upregulation medicine Animals business.industry General Neuroscience Subarachnoid Hemorrhage medicine.disease Triggering Receptor Expressed on Myeloid Cells-1 Rats 030104 developmental biology Matrix Metalloproteinase 9 Brain Injuries medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | Neuroscience. 406 |
| ISSN: | 1873-7544 |
| Popis: | Early 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect