Combined cell grafting and VPA administration facilitates neural repair through axonal regeneration and synaptogenesis in traumatic brain injury  

作　　者：Sujuan Liu Haili Tian Yanmei Niu Chunxia Yu Lingjian Xie Zhe Jin Wenyan Niu Jun Ren Li Fu Zhi Yao 

机构地区：[1]Department of Anatomy and Embryology,School of Basic Medical Science,Tianjin Medical University,Tianjin 300070,China [2]School of Kinesiology,Shanghai University of Sport,Shanghai 200438,China [3]Department of Rehabilitation,School of Medical Technology,Tianjin Medical University,Tianjin 300070,China [4]Department of Physiology and Pathophysiology,School of Basic Medical Science,Tianjin Medical University,Tianjin 300070,China [5]Tianjin Yaohua Binhai School,Tianjin 300000,China [6]Key Laboratory of Immune Microenvironment and Disease(Ministry of Education),Department of Immunology,School of Basic Medical Science,Tianjin Medical University,Tianjin 300070,China [7]Department of Cardiology,Zhongshan Hospital Fudan University,Shanghai Institute of Cardiovascular Diseases,Shanghai 200032,China [8]Department of Laboratory Medicine and Pathology,University of Washington,Seattle,WA 98195,USA

出　　处：《Acta Biochimica et Biophysica Sinica》2022年第9期1289-1300,共12页生物化学与生物物理学报（英文版）

基　　金：the grants from the China Postdoctoral Science Foundation(No.2019M661042);the National Natural Science Foundation of China(Nos.81501071,31871206 and 31671237).

摘　　要：Neuronal regeneration and functional recovery are severely compromised following traumatic brain injury(TBl).Treatment options,including cell transplantation and drug therapy,have been shown to benefit TBl,although the underlying mechanisms remain elusive.In this study,neural stem cells(NSCs)are transplanted into TBl-challenged mice,together with olfactory ensheathing cells(OECs)or followed by valproic acid(VPA)treatment.Both OEC grafting and VPA treatment facilitate the differentiation of NSCs into neurons(including endogenous and exogenous neurons)and significantly attenuate neurological functional defects in TBl mice.Combination of NSCs with OECs or VPA administration leads to overt improvement in axonal regeneration,synaptogenesis,and synaptic plasticity in the cerebral cortex in TBl-challenged mice,as shown by retrograde corticospinal tract tracing,electron microscopy,growth-associated protein 43(GAP43),and synaptophysin(SYN)analyses.However,these beneficial effects of VPA are reversed by local delivery of N-methyl-D-aspartate(NMDA)into tissues surrounding the injury epicenter in the cerebral cortex,accompanied by a pronounced drop in axons and synapses in the brain.Our findings reveal that increased axonal regeneration and synaptogenesis evoked by cell grafting and VPA fosters neural repair in a murine model of TBl.Moreover,VPA-induced neuroprotective roles are antagonized by exogenous NMDA administration and its concomitant decrease in the number of neurons of local brain,indicating that increased neurons induced by VPA treatment mediate axonal regeneration and synaptogenesis in mice after TBl operation.Collectively,this study provides new insights into NSC transplantation therapy for TBI.

关 键 词：traumatic brain injury TRANSPLANTATION neural stem cells valproic acid N-METHYL-D-ASPARTATE 

分 类 号：R651.15[医药卫生—外科学]