Ulinastatin Alleviates Early Brain Injury After Intracerebral Hemorrhage by Inhibiting Necroptosis and Neuroinflammation Via MAPK/NF-κB Signaling Pathway

Overview

Journal Acta Cir Bras

Specialty General Surgery

Date 2022 May 18

PMID 35584533

Authors

Li Wang

Wei Jiao

Jiayu Wu

Jing Zhang

Min Tang

Yang Chen

Affiliations

Soon will be listed here.

Abstract

Purpose: Spontaneous intracerebral hemorrhage (ICH) is a major public health problem with a huge economic burden worldwide. Ulinastatin (UTI), a serine protease inhibitor, has been reported to be anti-inflammatory, immune regulation, and organ protection by reducing reactive oxygen species production, and inflammation. Necroptosis is a programmed cell death mechanism that plays a vital role in neuronal cell death after ICH. However, the neuroprotection of UTI in ICH has not been confirmed, and the potential mechanism is unclear. The present study aimed to investigate the neuroprotection and potential molecular mechanisms of UTI in ICH-induced EBI in a C57BL/6 mouse model.

Methods: The neurological score, brain water content, neuroinflammatory cytokine levels, and neuronal damage were evaluated. The anti-inflammation effectiveness of UTI in ICH patients also was evaluated.

Results: UTI treatment markedly increased the neurological score, alleviate the brain edema, decreased the inflammatory cytokine TNF-α, interleukin‑1β (IL‑1β), IL‑6, NF‑κB levels, and RIP1/RIP3, which indicated that UTI-mediated inhibition of neuroinflammation, and necroptosis alleviated neuronal damage after ICH. UTI also can decrease the inflammatory cytokine of ICH patients. The neuroprotective capacity of UTI is partly dependent on the MAPK/NF-κB signaling pathway.

Conclusions: UTI improves neurological outcomes in mice and reduces neuronal death by protecting against neural neuroinflammation, and necroptosis.

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