J Neuroinflamm
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Two families of polyunsaturated fatty acid (PUFA), omega-3 (ω-3) and omega-6 (ω-6), are required for physiological functions. The long chain ω-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have significant biological effects. In particular, DHA is a major component of cell membranes in the brain. It is also involved in neurotransmission. Spinal cord injury (SCI) is a highly devastating pathology that can lead to catastrophic dysfunction, with a significant reduction in the quality of life. Previous studies have shown that EPA and DHA can exert neuroprotective effects in SCI in mice and rats. The aim of this study was to analyze the mechanism of action of ω-3 PUFAs, such as DHA, in a mouse model of SCI, with a focus on the early pathophysiological processes. ⋯ Our results, in vivo and in vitro, clearly demonstrate that DHA treatment reduces the development of inflammation and tissue injury associated with spinal cord trauma.
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Translocation of high-mobility group box 1 (HMGB1) from nucleus could trigger inflammation. Extracellular HMGB1 up-regulates inflammatory response in sepsis as a late mediator. However, little was known about its role in subarachnoid hemorrhage-inducible inflammation, especially in the early stage. This study aims to identify whether HMGB1 translocation occurred early after SAH and also to clarify the potential role of HMGB1 in brain injury following SAH. ⋯ HMGB1 was released from neurons early after SAH onset and might trigger inflammation as an upstream inflammatory mediator. Extracellular HMGB1 contributed to the brain injury after SAH. These results might have important implications during the administration of specific HMGB1 antagonists early in order to prevent or reduce inflammatory response following SAH.
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Traumatic brain injury (TBI) initiates a neuroinflammatory cascade that contributes to substantial neuronal damage and behavioral impairment, and Toll-like receptor 4 (TLR4) is an important mediator of thiscascade. In the current study, we tested the hypothesis that curcumin, a phytochemical compound with potent anti-inflammatory properties that is extracted from the rhizome Curcuma longa, alleviates acute inflammatory injury mediated by TLR4 following TBI. ⋯ Our results suggest that post-injury, curcumin administration may improve patient outcome by reducing acute activation of microglia/macrophages and neuronal apoptosis through a mechanism involving the TLR4/MyD88/NF-κB signaling pathway in microglia/macrophages in TBI.
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Sepsis- associated encephalopathy (SAE) is an early and common feature of severe infections. Oxidative stress is one of the mechanisms associated with the pathophysiology of SAE. The goal of this study was to investigate the involvement of NADPH oxidase in neuroinflammation and in the long-term cognitive impairment of sepsis survivors. ⋯ Our results demonstrate that Nox2 is the main source of reactive oxygen species (ROS) involved in the oxidative damage to the hippocampus in SAE and that Nox2-derived ROS are determining factors for cognitive impairments after sepsis. These findings highlight the importance of Nox2-derived ROS as a central mechanism in the development of neuroinflammation associated with SAE.
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Hypertonic saline (HS) has been successfully used clinically for treatment of various forms of cerebral edema. Up-regulated expression of Na-K-Cl Cotransporter 1 (NKCC1) and inflammatory mediators such as tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) has been demonstrated to be closely associated with the pathogenesis of cerebral edema resulting from a variety of brain injuries. This study aimed to explore if alleviation of cerebral edema by 10% HS might be effected through down-regulation of inflammatory mediator expression in the microglia, and thus result in decreased NKCC1 expression in astrocytes in the cerebral cortex bordering the ischemic core. ⋯ The results suggest that 10% HS alleviates cerebral edema through inhibition of the NKCC1 Cotransporter, which is mediated by attenuation of TNF-α and IL-1β stimulation on NKCC1.