Dectin-1/Syk signaling triggers neuroinflammation after ischemic stroke in mice

Abstract

Background: Dendritic cell-associated C-type lectin-1 (Dectin-1) receptor has been reported to be involved in neuroinflammation in Alzheimer's disease and traumatic brain injury. The present study was designed to investigate the role of Dectin-1 and its downstream target spleen tyrosine kinase (Syk) in early brain injury after ischemic stroke using a focal cortex ischemic stroke model. Methods: Adult male C57BL/6 J mice were subjected to a cerebral focal ischemia model of ischemic stroke. The neurological score, adhesive removal test, and foot-fault test were evaluated on days 1, 3, 5, and 7 after ischemic stroke. Dectin-1, Syk, phosphorylated (p)-Syk, tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) expression was analyzed via western blotting in ischemic brain tissue after ischemic stroke and in BV2 microglial cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) injury in vitro. The brain infarct volume and Iba1-positive cells were evaluated using Nissl's and immunofluorescence staining, respectively. The Dectin-1 antagonist laminarin (LAM) and a selective inhibitor of Syk phosphorylation (piceatannol; PIC) were used for the intervention. Results: Dectin-1, Syk, and p-Syk expression was significantly enhanced on days 3, 5, and 7 and peaked on day 3 after ischemic stroke. The Dectin-1 antagonist LAM or Syk inhibitor PIC decreased the number of Iba1-positive cells and TNF-α and iNOS expression, decreased the brain infarct volume, and improved neurological functions on day 3 after ischemic stroke. In addition, the in vitro data revealed that Dectin-1, Syk, and p-Syk expression was increased following the 3-h OGD and 0, 3, and 6 h of reperfusion in BV2 microglial cells. LAM and PIC also decreased TNF-α and iNOS expression 3 h after OGD/R induction. Conclusion: Dectin-1/Syk signaling plays a crucial role in inflammatory activation after ischemic stroke, and further investigation of Dectin-1/Syk signaling in stroke is warranted.

Effects of Cocaine on Human Glial-Derived Extracellular Vesicles

“…However, these studies were performed in BV2 microglial cells which suggests there may be differences that are cell line specific ( Baldwin et al, 2015 ). Dectin-1 is involved in neuroinflammation and secretory cellular processes and should be affected by cocaine administration ( Baldwin et al, 2015 ; Gensel et al, 2015 ; Ye et al, 2020 ). We demonstrated there was a decrease as predicted in the dectin-1 levels.…”

Inhibition of PDE1-B by Vinpocetine Regulates Microglial Exosomes and Polarization Through Enhancing Autophagic Flux for Neuroprotection Against Ischemic Stroke

“…It should be noted that we only used male mice in this study in order to avoid the effect of sex hormone ( Spychala et al, 2018 ; Zhang H. et al, 2018 ; Otxoa-de-Amezaga et al, 2019 ; Xu et al, 2019 ; Al Mamun et al, 2020 ; Ye et al, 2020 ). It has been reported that estrogen receptors (ERs) are widely distributed in the brain, present on both neurons and glia, and expressed by both sexes ( Rettberg et al, 2014 ; Hewitt and Korach, 2018 ).…”

Associations between serum L-arginine and ficolins in the early phase of acute ischemic stroke – A pilot study

“…In the hyperacute phase of AIS, we observed a positive correlation between ficolin-3, MAP-1, MBL and the NO donor L-arginine reflecting the protective role of L-arginine presumably by improving the cerebral microcirculation in a prothrombotic environment induced by complement activation. 25 Beside initiating activation of complement via the lectin pathway, ficolins may trigger activation of the immune system by production of nitric oxide (NO) by macrophages, thus limiting the infection and concurrently orchestrating the subsequent adaptive immune response. 26 In acute coronary syndrome, the kinetics of oxidized lowdensity lipoprotein receptor-1 (LOX-1), a lectin like molecule, was described with an acute increase up to 12 postevent hour and a subsequent decrease, while NOx derived from the L-arginine-nitric oxide pathway, decreased promptly suggesting an impaired NO metabolism during acute ischemic coronary event.…”