Placenta-derived mesenchymal stem cells attenuate secondary brain injury after controlled cortical impact in rats by inhibiting matrix metalloproteinases  

作　　者：PING YANG YUANXIANG LAN ZHONG ZENG YAN WANG HECHUN XIA 

机构地区：[1]Department of Neurosurgery,School of Clinical Medicine,Ningxia Medical University,Yinchuan,China [2]Key Laboratory of Ningxia Stem Cell and Regenerative Medicine,General Hospital of Ningxia Medical University,Yinchuan,China [3]Department of Neurosurgery,Xi’an International Medical Center Hospital,Xi’an,China

出　　处：《BIOCELL》2024年第1期149-162,共14页生物细胞（英文）

基　　金：financially supported by the Key Research Projects of Ningxia Hui Autonomous Region of China under Grant No.2018BCG01002(to HCX).

摘　　要：Background:As a form of biological therapy,placenta-derived mesenchymal stem cells(PDMSCs)exhibit considerable promise in addressing the complex pathological processes of traumaticbrain injury(TBI)due to their multi-target and multi-pathway mode of action.Material&Methods:This study investigates the protective mechanisms and benefits of PDMSCs in mitigating the effects of controlled cortical impact(CCI)in rats and glutamate-induced oxidative stress injury in HT22 cells in vitro.Our primary objective is to provide evidence supporting the clinical application of PDMSCs.Results:In the in vivo arm of our investigation,we observed a swift elevation of matrix metalloproteinase-9(MMP-9)in the proximal cortex of injured brain tissues after CCI.PDMSCs,distinguished by their heightened expression of metalloproteinase tissue inhibitors-1 and-2(TIMP-1 and TIMP-2):were intravenously administered via the caudal vein.This intervention yielded significant reductions in the permeability of the blood-brain barrier(BBB):the extent of brain edema,the levels of inflammatory cytokines IL-1βand TNF-αin damaged brain tissue,and the activation status of microglia in CCI-afflicted rats.In the realm of in vitro experiments,PDMSC-conditioned media demonstrated substantial reductions in mortality rates and cleaved caspase-3 levels in glutamate-induced HT22 cells compared with conventional media.Notably,this advantage was negated upon the introduction of neutralizing antibodies targeting TIMP-1 and TIMP-2.Conclusion:Collectively,our findings underscore the potential of PDMSCs in alleviating oxidative stress injury and secondary brain injury in the pathological process of TBI.

关 键 词：Traumatic brain injury Mesenchymal stem cells Oxidative stress Matrix metalloproteinases 

分 类 号：R651.15[医药卫生—外科学]