Abstract
BackgroundDendritic 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.MethodsAdult 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.ResultsDectin-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.ConclusionDectin-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.
Highlights
In recent decades, ischemic stroke has become one of the most common causes of disability and mortality worldwide
Dectin-1 is significantly increased in the ischemic brain tissue after stroke and the BV2 microglial cells after OGD/ R-induced injury in vitro In order to investigate the potential role of Dectin-1 in the progression of ischemic stroke, the present study first examined the Dectin-1 protein levels in ischemic brain tissue and BV2 cells in the oxygen-glucose deprivation/reoxygenation (OGD/R) model
spleen tyrosine kinase (Syk) and p-Syk are significantly upregulated in the ischemic brain tissue after stroke and BV2 microglial cells with OGD/R-induced injury in vitro In order to investigate whether Syk signaling was involved in the progression of ischemic stroke, the Syk and p-Syk protein levels were tested in ischemic brain tissue and BV2 cells in the OGD/R model in the present study
Summary
Ischemic stroke has become one of the most common causes of disability and mortality worldwide. The pathophysiology of cerebral ischemic injury is multifactorial, increasing studies have suggested that the inflammatory response plays a crucial role in stroke progression [1, 2]. Previous studies have reported that immune receptors that initiate the inflammatory response play an important role in stroke progression [13,14,15,16]. To the best of our knowledge, whether the immune receptor Dectin-1 is involved in the inflammatory response following a stroke has not yet been investigated. 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
