Stroke is the major cause of death and disability worldwide.Most stroke patients who survive in the acute phase of ischemia display various extents of neurological deficits.In order to improve the prognosis of ischemic stroke,promoting endogenous neurogenesis has attracted great attention.Salvianolic acid A(SAA)has shown neuroprotective effects against ischemic diseases.In the present study,we investigated the neurogenesis effects of SAA in ischemic stroke rats,and explored the underlying mechanisms.An autologous thrombus stroke model was established by electrocoagulation.The rats were administered SAA(10 mg/kg,ig)or a positive drug edaravone(5 mg/kg,iv)once a day for 14 days.We showed that SAA administration significantly decreased infarction volume and vascular embolism,and ameliorated pathological injury in the hippocampus and striatum as well as the neurological deficits as compared with the model rats.Furthermore,we found that SAA administration significantly promoted neural stem/progenitor cells(NSPCs)proliferation,migration and differentiation into neurons,enhanced axonal regeneration and diminished neuronal apoptosis around the ipsilateral subventricular zone(SVZ),resulting in restored neural density and reconstructed neural circuits in the ischemic striatum.Moreover,we revealed that SAA-induced neurogenesis was associated to activating Wnt3a/GSK3β/β-catenin signaling pathway and downstream target genes in the hippocampus and striatum.Edaravone exerted equivalent inhibition on neuronal apoptosis in the SVZ,as SAA,but edaravone-induced neurogenesis was weaker than that of SAA.Taken together,our results demonstrate that long-term administration of SAA improves neurological function through enhancing endogenous neurogenesis and inhibiting neuronal apoptosis in ischemic stroke rats via activating Wnt3a/GSK3β/β-catenin signaling pathway.SAA may be a potential therapeutic drug to promote neurogenesis after stroke.

Sen Zhang;De-wen Kong;Guo-dong Ma;Cheng-di Liu;Yu-jiao Yang;Shan Liu;Nan Jiang;Zi-rong Pan;Wen Zhang;Ling-lei Kong;Guan-hua Du

Beijing Key Laboratory of Drug Targets Identification and Drug Screening,Institute of Materia Medica,Chinese Academy of Medical Science and Peking Union Medical College,Beijing 100050,China;College of Traditional Chinese Medicine,Guangdong Pharmaceutical University,Guangzhou 510006,China;School of Pharmacy,Henan University,Zhengzhou 475004,China

中国药理学报（英文版）

[1]Sen Zhang;De-wen Kong;Guo-dong Ma;Cheng-di Liu;Yu-jiao Yang;Shan Liu;Nan Jiang;Zi-rong Pan;Wen Zhang;Ling-lei Kong;Guan-hua Du-.Long-term administration of salvianolic acid A promotes endogenous neurogenesis in ischemic stroke rats through activating Wnt3a/GSK3β/β-catenin signaling pathway)[J].中国药理学报（英文版）,2022(09):2212-2225

NSPCs,Edaravone

Long,term,administration,salvianolic,acid,promotes,endogenous,neurogenesis,ischemic,stroke,rats,through,activating,Wnt3a,GSK3,catenin,signaling,pathway,Stroke,major,cause,death,disability,worldwide,Most,patients,who,survive,acute,phase,ischemia,display,various,extents,neurological,deficits,In,order,prognosis,promoting,attracted,great,attention,Salvianolic,SAA,shown,neuroprotective,effects,against,diseases,present,study,investigated,explored,underlying,mechanisms,An,autologous,thrombus,model,was,established,by,electrocoagulation,were,administered,positive,drug,edaravone,once,days,We,showed,that,significantly,decreased,infarction,volume,vascular,embolism,ameliorated,pathological,injury,hippocampus,striatum,well,compared,Furthermore,found,promoted,neural,stem,progenitor,cells,proliferation,migration,differentiation,into,neurons,enhanced,axonal,regeneration,diminished,neuronal,apoptosis,around,ipsilateral,subventricular,zone,SVZ,resulting,restored,density,reconstructed,circuits,Moreover,revealed,induced,associated,downstream,target,exerted,equivalent,inhibition,but,weaker,than,Taken,together,our,results,demonstrate,long,improves,function,enhancing,inhibiting,may,be,potential,therapeutic,after

0.540307