Activation of the wnt/β-catenin/CYP1B1 pathway alleviates oxidative stress and protects the blood-brain barrier under cerebral ischemia/reperfusion conditions

Accumulating evidence suggests that oxidative stress and the Wnt/β-catenin pathway participate in stroke-induced disruption of the blood-brain barrier.However,the potential links between them following ischemic stroke remain largely unknown.The present study found that cerebral ischemia leads to oxidative stress and repression of the Wnt/β-catenin pathway.Meanwhile,Wnt/β-catenin pathway activation by the pharmacological inhibito r,TWS119,relieved oxidative stress,increased the levels of cytochrome P4501B1(CYP1B1)and tight junction-associated proteins(zonula occludens-1[ZO-1],occludin and claudin-5),as well as brain microvascular density in cerebral ischemia rats.Moreove r,rat brain microvascular endothelial cells that underwent oxygen glucose deprivation/reoxygenation displayed intense oxidative stress,suppression of the Wnt/β-catenin pathway,aggravated cell apoptosis,downregulated CYP1B1and tight junction protein levels,and inhibited cell prolife ration and migration.Overexpression ofβ-catenin or knockdown ofβ-catenin and CYP1B1 genes in rat brain mic rovascular endothelial cells at least partly ameliorated or exacerbated these effects,respectively.In addition,small interfering RNA-mediatedβ-catenin silencing decreased CYP1B1 expression,whereas CYP1B1 knoc kdown did not change the levels of glycogen synthase kinase 3β,Wnt-3a,andβ-catenin proteins in rat brain microvascular endothelial cells after oxygen glucose deprivatio n/reoxygenation.Thus,the data suggest that CYP1B1 can be regulated by Wnt/β-catenin signaling,and activation of the Wnt/β-catenin/CYP1B1 pathway contributes to alleviation of oxidative stress,increased tight junction levels,and protection of the blood-brain barrier against ischemia/hypoxia-induced injury.

Effects of creative expression program on the event-related potential and task reaction time of elderly with mild cognitive impairment

Objectives:This study aimed to evaluate the effects of a 16-week creative expression intervention program(CrExp)on the event-related potential(ERP)and task reaction time in older individuals with mild cognitive impairment(MCI).Methods:This study is a randomized controlled clinical trial conducted in the Memory Center of Fujian Provincial hospital.Thirty-six MCI patients were randomly distributed into two groups.One group underwent a 16-week creative expression program(CrExp,n=18)and the other performed as a control group(CG,n=18)by general social activities.The amplitude and latency of ERP-P300 from the central(Cz),parietal(Pz),frontal(Fz)cortices and task reaction time(RT)were assessed at baseline,postinterventi on,and 24-week follow-up.Results:The CrExp group showed greater differences than CG of P300 latency in Cz(F=4.37,P=0.015),Pz(F=2.78,P=0.009),Fz(F=6.45,P=0.031)brain area after 16 weeks of intervention and in Fz(F=3.23,P=0.028),Cz(F=3.79,P=0.024),and Pz(F=5.60,P=0.036)at 24 weeks follow-up.Also,we analyzed the task reaction time between two groups and found that a shorten reaction time at postintervention(F=4.47,P=0.011)and 24 weeks follow-up(F=3.12,P=0.007)in the CrExp group.However,there was no difference in P300 amplitude in either brain area between the two groups.Conclusion:The electrophysiological results of the creative expression cognitive therapy group were more obvious than those of the general cognitive therapy group,and the latency and task reaction time may be considered as supported parameters in diagnosing the effects during non-drug therapy intervention in clinical practice.