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Inhibition of activator protein 1 attenuates neuroinflammation and brain injury after experimental intracerebral hemorrhage
AIMS: Intracerebral hemorrhage (ICH) is a devastating type of stroke without specific treatment. Activator protein 1 (AP‐1), as a gene regulator, initiates cytokine expression in response to environmental stimuli. In this study, we investigated the relationship between AP‐1 and neuroinflammation‐ass...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776742/ https://www.ncbi.nlm.nih.gov/pubmed/31392841 http://dx.doi.org/10.1111/cns.13206 |
Sumario: | AIMS: Intracerebral hemorrhage (ICH) is a devastating type of stroke without specific treatment. Activator protein 1 (AP‐1), as a gene regulator, initiates cytokine expression in response to environmental stimuli. In this study, we investigated the relationship between AP‐1 and neuroinflammation‐associated brain injury triggered by ICH. METHODS: Intracerebral hemorrhage mice were developed by autologous blood or collagenase infusion. We measured the dynamics of AP‐1 in mouse brain tissues during neuroinflammation formation after ICH. The effects of the AP‐1 inhibitor SR11302 on brain injury and neuroinflammation as well as the underlying mechanisms were investigated in vivo and in vitro. RESULTS: AP‐1 was significantly upregulated in mouse brain tissue as early as 6 hours after ICH, accompanied by elevations in proinflammatory factors, including interleukin (IL)‐6, IL‐1β, and tumor necrosis factor (TNF)‐α. Inhibition of AP‐1 using SR11302 reduced neurodeficits and brain edema at day 3 after ICH. SR11302 ablated microglial IL‐6 and TNF‐α production and brain‐infiltrating leukocytes in ICH mice. In addition, SR11302 treatment diminished thrombin‐induced production of IL‐6 and TNF‐α in cultured microglia. CONCLUSIONS: Inhibition of AP‐1 curbs neuroinflammation and reduces brain injury following ICH. |
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