β2-Microglobulin exacerbates neuroinflammation,brain damage,and cognitive impairment after stroke in rats

β2-Microglobulin(β2M),a component of the major histocompatibility complex class I molecule,is associated with aging-related cognitive impairment and Alzheimer’s disease.Although upregulation ofβ2M is considered to be highly related to ischemic stroke,the specific role and underlying mechanistic action ofβ2M are poorly understood.In this study,we established a rat model of focal cerebral ischemia by occlusion of the middle cerebral artery.We found thatβ2M levels in the cerebral spinal fluid,serum,and brain tissue were significantly increased in the acute period but gradually decreased during the recovery period.RNA interference was used to inhibitβ2M expression in the acute period of cerebral stroke.Tissue staining with 2,3,5-triphenyltetrazolium chloride and evaluation of cognitive function using the Morris water maze test demonstrated that decreasedβ2M expression in the ischemic penumbra reduced infarct volume and alleviated cognitive deficits,respectively.Notably,glial cell,caspase-1(p20),and Nod-like receptor pyrin domain containing 3(NLRP3)inflammasome activation as well as production of the inflammatory cytokines interleukin-1β,interleukin-6,and tumor necrosis factor-αwere also effectively inhibited byβ2M silencing.These findings suggest thatβ2M participates in brain injury and cognitive impairment in a rat model of ischemic stroke through activation of neuroinflammation associated with the NLRP3 inflammasome.

The Potential Immunomodulatory Properties of Levornidazole Contribute to Improvement in Experimental Ulcerative Colitis

The use of an antibiotic with immunomodulatory properties could be fascinating in treating multifactorial inflammatory conditions such as ulcerative colitis(UC).We report our investigations into the immunomodulatory properties of levornidazole,the S-enantiomer of ornidazole,which displayed a tremendous therapeutic potential in UC induced by dextran sodium sulfate(DSS).Levornidazole administration to DSS-colitic mice attenuated the intestinal inflammatory process,with an efficacy better than that shown by 5-amino salicylic acid.This was evidenced by decreased disease activity index,ameliorated macroscopic and microscopic colon damages,and reduced expression of inflammatory cytokines.Additionally,levornidazole displayed anti-inflammatory activity through Caveolin-1-dependent reducing IL-1βand IL-18 secretion by macrophages contributing to its improvement of the intestinal inflammation,as confirmed in vitro and in vivo.In conclusion,these results pointed out that the immunomodulatory effects of levornidazole played a vital role in ameliorating the intestinal inflammatory process,which would be crucial for the translation of its use into clinical settings.