HMGB1 mediates blood-brain barrier disruption in septic mice via TLR4/eNOS signaling pathway
Objective To investigate the role of high mobility group box-1(HMGB1)in the pathogenesis of sepsis-asso-ciated encephalopathy(SAE).Methods Adult male C57BL/6J mice were randomly divided into 4 groups:Sham(vehicle pre-treatment for 1 day,sham operation),Sham+ICM(Inflachromene 10 mg/kg pretreatment for 1 day,sham operation),cecal ligation and puncture(CLP)(vehicle pretreatment for 1 day,cecal ligation and puncture CLP modeling),and CLP+ICM(In-flachromene 10 mg/kg pretreatment for 1 day,CLP modeling).Morris water maze was used to evaluate spatial memory func-tion,and open field test was used to assess spontaneous activity.On the first day after surgery,blood-brain barrier permeability was evaluated through leakage experiments.Western blot was used to detect the expression levels of tight junction proteins(ZO-1,Occludin,and Claudin-5)in the cerebral cortex,as well as Toll-like receptor 4(TLR4)and endothelial nitric oxide synthase(eNOS).Results Compared with the CLP group,the CLP+ICM group exhibited shortened latency in the water maze positio-ning navigation experiment,increased target quadrant dwelling time,and increased platform crossing times in the spatial probe test.On the first day after surgery,blood-brain barrier permeability was reduced;the expression of ZO-1,Occludin,and Clau-din-5 in the cerebral cortex was upregulated;and the expression levels of TLR4 and eNOS were downregulated.Conclusion HMGB1 may mediate blood-brain barrier damage in septic mice by activating the TLR4/eNOS pathway,thereby promoting the occurrence of SAE.
cognitive dysfunctionhigh mobility group box-1 proteinblood-brain barriersepsis-associated encephalopa-thy
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