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- W3199924656 abstract "Abstract Background Our previous studies demonstrated that intraventricular injection of thrombin could induce hydrocephalus. The inflammation of subarachnoid space plays a key role in hydrocephalus. As thrombin, inducing coagulation, could contribute to inflammation, its effects on subarachnoid space have not been well studied. Macrophagic dysfunction may contribute to this course. However, the mechanisms that how thrombin affects macrophage in subarachnoid space have not been illustrated. Our aim was to explore the possible role that macrophage played in thrombin-induced meningeal inflammation, and to furtherly understand its contribution during thrombin-induced hydrocephalus. Methods There were two parts in this study. Firstly, rats had an intraventricular injection of saline or thrombin. Secondly, rats received thrombin injection with vehicle or PAR1 antagonist treatment. Immunofluorescence staining was applied to observe the activation of meningeal macrophage and the expression of NeuN in the cortex. Meanwhile, the expression of intercellular adhesion molecule 1 (ICAM1) in meningeal vessels were tested to detect the vascular inflammation. Western blot was applied to measure the secretion of pro-inflammatory cytokines (IL-1β and IFNγ). Results Our results demonstrated that intraventricular injection of thrombin caused significant activation of meningeal macrophages, vascular inflammation, and neuron loss. Inhibition of PAR1 pathway attenuated the M1 polarization of meningeal macrophage, reduced the inflammatory infiltrations and prevented the neuron loss, as well as hydrocephalus after thrombin injection. Conclusions Clinically available PAR1 antagonists may offer a novel therapeutic approach candidate for the prevention or the management of inflammation in hemorrhage-induced hydrocephalus." @default.
- W3199924656 created "2021-09-27" @default.
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- W3199924656 date "2020-02-12" @default.
- W3199924656 modified "2023-10-16" @default.
- W3199924656 title "Inhibition of PAR1 attenuates meningeal macrophage activation and vascular inflammation in a rat model of thrombin-induced hydrocephalus" @default.
- W3199924656 doi "https://doi.org/10.21203/rs.2.19125/v2" @default.
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