BackgroundCerebral ischemia is a leading cause of death and disability with limited treatment options. Although inflammatory and immune responses participate in ischemic brain injury, the molecular regulators of neuroinflammation after ischemia remain to be defined. Translocator protein 18 kDa (TSPO) mainly localized to the mitochondrial outer membrane is predominantly expressed in glia within the central nervous system during inflammatory conditions. This study investigated the effect of a TSPO agonist, etifoxine, on neuroinflammation and brain injury after ischemia/reperfusion.MethodsWe used a mouse model of middle cerebral artery occlusion (MCAO) to examine the therapeutic potential and mechanisms of neuroprotection by etifoxine.ResultsTSPO was upregulated in Iba1+ or CD11b+CD45int cells from mice subjected to MCAO and reperfusion. Etifoxine significantly attenuated neurodeficits and infarct volume after MCAO and reperfusion. The attenuation was pronounced in mice subjected to 30, 60, or 90 min MCAO. Etifoxine reduced production of pro-inflammatory factors in the ischemic brain. In addition, etifoxine treatment led to decreased expression of interleukin-1β, interleukin-6, tumor necrosis factor-α, and inducible nitric oxide synthase by microglia. Notably, the benefit of etifoxine against brain infarction was ablated in mice depleted of microglia using a colony-stimulating factor 1 receptor inhibitor.ConclusionsThese findings indicate that the TSPO agonist, etifoxine, reduces neuroinflammation and brain injury after ischemia/reperfusion. The therapeutic potential of targeting TSPO requires further investigations in ischemic stroke.
Traditional Chinese Medicine (TCM) has long perceived environment as an integral part of the development of body constitution, which is a personal state of health closely related to disease presence. Despite of the ever-growing studies on the clinical effectiveness of TCM and the scientific linking between body constitution and diseases, the geographical influence on body constitution has yet remained an unexplored territory. This study sought to investigate whether the neighbourhood environment is relevant to the composition of body type of a population through statistical multilevel and Geographic Information Systems modelling. The analysis comprised 3277 participants who had completed their body type assessment between 2009 and 2012 inclusive. The multilevel analysis also took simultaneous accounts of both individual-level (gender, age, BMI, type of housing) and area-level (percent greenery, percent road surface, total road intersection, sky view factor, temperature, relative humidity, rainfall and social deprivation index) characteristics to explain geographical variation by body types. Significant random or place effects (p < 0.001) were identified in the multilevel models. The spatial variation of body constitution involved the dynamic interplay between individual and environmental factors. The findings amassed the first scientific indications to back the common belief that place does play a role in the development of body constitution and is worthy of further investigation. By considering spatial and personal attributes simultaneously, the study can yield valuable insights into the patterning of area variation in body constitution and disease presence.
There is a growing change trend in the number of studies on CDSS research in recent two decades, most of which are non-comparative studies (46.10%) . Only 21 systematic reviews and 22 randomized controlled trails were published with the percentage of 3.41% and 3.57% of the included studies. More methodologically rigorous designs are needed to improve the research quality on CDSS.
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