Journal: BJA: British Journal of Anaesthesia

Article Title: Maresin 1 attenuates neuroinflammation in a mouse model of perioperative neurocognitive disorders

doi: 10.1016/j.bja.2018.10.062

Figure Lengend Snippet: Anti-inflammatory and pro-resolving effects of maresin 1 prophylaxis. (a) Study design and endpoints. (b–e) Time course of plasma levels of interleukin (IL)-6, IL-12, CXCL1, and IL-10 at 24 h, 72 h, and 14 days after orthopaedic surgery. (f) Cognitive evaluation of mice using contextual fear conditioning. Training was performed before surgery and hippocampus-dependent memory was assessed at 72 h. MaR1 prevented surgery-induced cognitive dysfunction in both wild-type mice and (g) Ccr2 RFP/+ Cx3cr1 GFP/+ transgenic mice. (h–i) Effects of MaR1 on bone healing 14 days after stabilised tibia fracture surgery. Arrows indicate the original cortical bone. Scale bar: 50 μm. Data expressed as mean ( sem ); * P <0.05; n =5–6 per group (** P <0.01, n =8–10 for behaviour). C, Control; MaR1, Maresin 1; S, Surgery; sem , standard error of the mean.

Article Snippet: Separate batches of BMDMs were stimulated with LPS (10 ng ml −1 ) or 20 ng mL −1 recombinant mouse interleukin (IL)-4, IL-10, and recombinant human transforming growth factor (TGF)-β1 (R&D Systems) for 24 h and macrophage activation surface marker expression was assessed using flow cytometry.

Techniques: Transgenic Assay

Journal: BJA: British Journal of Anaesthesia

Article Title: Maresin 1 attenuates neuroinflammation in a mouse model of perioperative neurocognitive disorders

doi: 10.1016/j.bja.2018.10.062

Figure Lengend Snippet: Maresin 1 effects on bone marrow-derived macrophages (BMDMs). (a) Representative images of immunostaining of NF-κB in BMDMs. Stimulated with 10 ng ml −1 LPS for 2 h. (b) 2 h of LPS stimulation (10 ng ml −1 ) significantly increased NF-κB nuclear translocation in BMDMs. (c) LPS caused significant increase of TNF-α release from BMDMs after 24 h stimulation, which was reduced by co-application of MaR1 (10 nM). (d) NADPH oxidase mediated superoxide production in BMDMs was significantly increased after 24 h of LPS stimulation, which was inhibited by MaR1 co-application. (e–h) MaR1 reduced LPS-induced PD-L1 and CD86 expression in BMDMs at 24 h. No significant effect of MaR1 on PD-L2 and CD206 expression in BMDMs stimulated by M2 polarisation cytokines (IL-4/IL-10/TGF-β). Data are expressed as mean ( sem ). * P <0.05, ** P <0.01; n =3–5 per group. CLU, chemiluminescence unit; IL, interleukin; LPS, lipopolysaccharide; MaR1, Maresin 1; MFI, median fluorescence intensity; NADPH, nicotinamide adenine dinucleotide phosphate; sem , standard error of the mean; TNF, tumour necrosis factor.

Article Snippet: Separate batches of BMDMs were stimulated with LPS (10 ng ml −1 ) or 20 ng mL −1 recombinant mouse interleukin (IL)-4, IL-10, and recombinant human transforming growth factor (TGF)-β1 (R&D Systems) for 24 h and macrophage activation surface marker expression was assessed using flow cytometry.

Techniques: Derivative Assay, Immunostaining, Translocation Assay, Expressing, Fluorescence

Journal: BJA: British Journal of Anaesthesia

Article Title: Maresin 1 attenuates neuroinflammation in a mouse model of perioperative neurocognitive disorders

doi: 10.1016/j.bja.2018.10.062

Figure Lengend Snippet: Maresin 1 levels in CSF before, 24 h, and 6 weeks after major non-cardiac, non-neurologic surgery in older patients (age ≥60 yr). (a) Each line represents a single patient. Diagonal cross marks on the X and Y axes indicate non-linearity/scale discontinuity. n =11. (b) Working model for MaR1 protection in PNDs. Pre-treatment with MaR1 regulated excessive inflammation from circulating macrophage by reducing NF-κB activation, oxidative stress, pro-inflammatory cytokine release, overall contributing to a ‘M2-like’ switch. This systemic milieu did not impair fracture healing or cause signs of immunosuppression. In fact, these systemic effects prevented loss of cld-5 expression at the blood–brain barrier (BBB) and macrophage infiltration into the brain parenchyma. Overall, dampening the postoperative neuroinflammation leads to improved cognitive function. CSF, cerebrospinal fluid; IL, interleukin; MaR1, Maresin 1; NF-κB, nuclear factor-kappa B; PNDs, perioperative neurocognitive disorders; ROS, reactive oxygen species.

Article Snippet: Separate batches of BMDMs were stimulated with LPS (10 ng ml −1 ) or 20 ng mL −1 recombinant mouse interleukin (IL)-4, IL-10, and recombinant human transforming growth factor (TGF)-β1 (R&D Systems) for 24 h and macrophage activation surface marker expression was assessed using flow cytometry.

Techniques: Activation Assay, Expressing