Carotid artery transplantation of brain endothelial cells enhances neuroprotection and neurorepair in ischaemic stroke rats  

作　　者：Yi-ting Du Zhi-guang Pan Bin-chi Chen Feng-yan Sun 

机构地区：[1]Department of Neurobiology and Research Institute for Aging and Medicine,School of Basic Medical Sciences,Shanghai Medical College,Fudan University,Shanghai 200032,China [2]National Clinical Research Center for Aging and Medicine,Shanghai Medical College,Fudan University,Shanghai 200032,China [3]Shanghai Key Laboratory of Bioactive Small Molecules,School of Basic Medical Sciences and Institute of Biomedical Sciences,Shanghai Medical College,Fudan University,Shanghai 200032,China [4]Department of Neurosurgery,Hua-Shan Hospital,Shanghai Medical College,Fudan University,Shanghai 200032,China

出　　处：《Acta Pharmacologica Sinica》2024年第12期2487-2496,共10页中国药理学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(81030020,81571197,and 81771268);The Shanghai Key Laboratory Program of the Education Commission of Shanghai Municipality(ZDSS14005).

摘　　要：Brain microvascular endothelial cells(BMECs),an important component of the neurovascular unit,can promote angiogenesis and synaptic formation in ischaemic mice after brain parenchyma transplantation.Since the therapeutic efficacy of cell-based therapies depends on the extent of transplanted cell residence in the target tissue and cell migration ability,the delivery route has become a hot research topic.In this study,we investigated the effects of carotid artery transplantation of BMECs on neuronal injury,neurorepair,and neurological dysfunction in rats after cerebral ischaemic attack.Purified passage 1 endothelial cells(P1-BMECs)were prepared from mouse brain tissue.Adult rats were subjected to transient middle cerebral artery occlusion(MCAO)for 30 min.Then,the rats were treated with 5×105 P1-BMECs through carotid artery infusion or tail vein injection.We observed that carotid artery transplantation of BMECs produced more potent neuroprotective effects than caudal injection in MCAO rats,including reducing infarct size and alleviating neurological deficits in behavioural tests.Carotid artery-transplanted BMECs displayed a wider distribution in the ischaemic rat brain.Immunostaining for endothelial progenitor cells and the mature endothelial cell markers CD34 and RECA-1 showed that carotid artery transplantation of BMECs significantly increased angiogenesis.Carotid artery transplantation of BMECs significantly increased the number of surviving neurons,decreased the cerebral infarction volume,and alleviated neurological deficits.In addition,we found that carotid artery transplantation of BMECs significantly enhanced ischaemia-induced hippocampal neurogenesis,as measured by doublecortin(DCX)and Ki67 double staining within 2 weeks after ischaemic injury.We conclude that carotid artery transplantation of BMECs can promote cerebral angiogenesis,neurogenesis,and neurological function recovery in adult rats after ischaemic stroke.Our results suggest that carotid injection of BMECs may be a promising new approach for trea

关 键 词：brain stroke endothelial cell therapy carotid artery transplantation neurovascular unit NEUROREPAIR 

分 类 号：R743.3[医药卫生—神经病学与精神病学]