Aim To investigate the effect of oleoylethanolamide (OEA),a new PPAR? agonist,on focal cerebral ischemia in mice.Methods Transient focal cerebral ischemia in mice was induced by middle cerebral artery occlusion for 1.5 h. OEA was orally administered either with multiple doses (10,20,40 mg?kg-1) once a day for 3 days before ischemia or single dose (40 mg?kg-1) at 0.5 h before or 1 h before ischemic,the same time of reperfusion or 1 h after reperfusion respectively.Neurological deficit score,infarct volume and brain edema were determined.Results Pretreatment with multiple doses (20,40 mg?kg-1) of OEA before ischemia or single dose (40 mg?kg-1) of OEA at 0.5 h before ischemia or at the same time of reperfusion significantly attenuated neurological deficit score,decreased infarct volume and alleviated brain edema,and the treatment at the time of reperfusion had the most marked effect.Conclusion Oleoylethano-lamide has a dose-and time-dependent neuroprotective effect on the injury in the acute phase of transient focal cerebral ischemia in mice,with effective doses of 20 mg?kg-1 and 40 mg?kg-1 and the optimal therapeutic time point of the same time of reperfusion.

purpose To investigate the protective effect and character of dl-praeruptorin A(Pd-Ia)on focal cerebral ischemia in mice.Methods Transient focal cerebral ischemia in mice WaS induced by middle cerebral artery occlusion for 1.5 h.Pd-Ia was administered intraperitoneally either with multiple doses(1,5 and 10ms/ks)at 0.5 h before ischemia or single dose(5 ms/kg)at 0.5 h and 1 h before ischemic,the same time of ischemia,the same time of reperfusion,or 0.5 h and 1 h after reperfusion respectively.Neurological deficit score,infarct volume,brain edema,the activities of SOD and the contents of MDA were determined.Results Pretreatment with multiple doses(5 and 10 ms/ks)of Pd-Ia at 0.5 h before ischemia or single dose(5 mg/kg)of Pd-Ia at 0.5 h before ischemia,at the same time of ischemic,at the same time of reperfusion and 0.5 h after reperfusion significantly attenuated neurological deficit score,decreased infarct volume and alleviated brain edema,and the treatment at the time of reperfusion had the most marked effect.Pd-Ia(5 or 10 ms/ks)can significantly enhance the activities of SOD and lower the contents MDA.Conclusion dl-praeruptorin A has a neuroprotective effect on the injury in the acute phase of transient focal cerebral ischemia in mice,with optimal doses of 5 ms/ks and the optimal therapeutic time point of the same time of reperfusion.

Circadian rhythm is involved in the development and diseases of many tissues. However, as an essential environmental regulating factor, its effect on amelogenesis has not been fully elucidated. The present study aims to investigate the correlation between circadian rhythm and ameloblast differentiation and to explore the mechanism by which circadian genes regulate ameloblast differentiation. Circadian disruption models were constructed in mice for in vivo experiments. An ameloblast-lineage cell (ALC) line was used for in vitro studies. As essential molecules of the circadian system, Bmal1 and Per2 exhibited circadian expression in ALCs. Circadian disruption mice showed reduced amelogenin (AMELX) expression and enamel matrix secretion and downregulated expression of BMAL1, PER2, PPARγ, phosphorylated AKT1 and β-catenin, cytokeratin-14 and F-actin in ameloblasts. According to previous findings and our study, BMAL1 positively regulated PER2. Therefore, the present study focused on PER2-mediated ameloblast differentiation and enamel formation. Per2 knockdown decreased the expression of AMELX, PPARγ, phosphorylated AKT1 and β-catenin, promoted nuclear β-catenin accumulation, inhibited mineralization and altered the subcellular localization of E-cadherin in ALCs. Overexpression of PPARγ partially reversed the above results in Per2-knockdown ALCs. Furthermore, in in vivo experiments, the length of incisor eruption was significantly decreased in the circadian disturbance group compared to that in the control group, which was rescued by using a PPARγ agonist in circadian disturbance mice. In conclusion, through regulation of the PPARγ/AKT1/β-catenin signalling axis, PER2 played roles in amelogenin expression, cell junctions and arrangement, enamel matrix secretion and mineralization during ameloblast differentiation, which exert effects on enamel formation.