Inhibition of activator protein 1 attenuates neuroinflammation and brain injury after experimental intracerebral hemorrhage
Abstract
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. 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. 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. Inhibition of AP-1 curbs neuroinflammation and re...Continue Reading
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Brain Injury & Trauma
brain injury after impact to the head is due to both immediate mechanical effects and delayed responses of neural tissues.