Human Neural Stem Cell-Derived Exosomes Improve Cognitive Function In Vascular Dementia Mice

Objective/Background:Vascular dementia(VD)is a degenerative cerebrovascular disease that leads to cognitive impairment and memory loss.At present,it is the second largest form of dementia(at least 20%)after Alzheimer’s disease(AD).However,there is still no good treatment to slow down or reverse the damage caused by vascular dementia,and Ginkgo biloba extract is one of the drugs with certain therapeutic effect on vascular dementia.The purpose of this study is to explore the therapeutic effect of human neural stem cell-derived exosomes(NSC-Exo)on vascular dementia in vivo.Methods:Human neural stem cells(hNSCs)were isolated and cultured,and their markers were identified by immunofluorescence.The supernatant of neural stem cell culture medium was collected,and the exosomes derived from neural stem cells(hNSCs-Exo)were extracted from the supernatant.Nanoparticle size analysis(NTA)and Western blot were used to identify the size of exosomes and surface marker proteins.The model of vascular dementia(VD)in mice was established.hNSCs-Exo and ginkgolide B were injected into mice via tail vein and ginkgolide B was delivered into VD mice by gavage.The recovery of cognitive and memory functions in mice was evaluated by water maze and Y maze.Evaluation of apoptosis and regeneration of brain neurons in mice by immunofluorescence.Results:The neural stem cells cultured in the culture medium are spherical,that is,they express characteristic markers Nestin and SOX2,and have the ability to differentiate into other cells in the nervous system(neurons,astrocytes and oligodendrocytes,etc.).The shape and size of hNSC-Exo meet the criteria of exosomes.The results in WB showed that hNSC-Exo expressed CD63,TSG101 and CD9.In vivo experiments show that hNSC-Exo can better improve the cognitive and memory functions of VD mice,and promote the regeneration of neurons and synapses,compared with ginkgolide B administered in different ways.Conclusion:This study preliminarily confirmed that exosomes derived from human neural stem cells can improve the cognitive and memory functions of vascular dementia mice.