title: Adipose-derived mesenchymal stem cells reduce neuronal death after transient global cerebral ischemia through prevention of blood-brain barrier disruption and endothelial damage.
abstract: Global cerebral ischemia (GCI) is the leading cause of a poor prognosis even after successful resuscitation from cardiac arrest. Therapeutic induction of hypothermia (TH) is the only proven therapy-and current standard care-for GCI after cardiac arrest; however, its application has been significantly limited owing to technical difficulties. Mesenchymal stem cells (MSCs) are known to suppress neuronal death after cerebral ischemia. The prevention of blood-brain barrier (BBB) disruption has not been suggested as a mechanism of MSC treatment but has for TH. We evaluated the therapeutic effect of MSC administration on BBB disruption and neutrophil infiltration after GCI. To evaluate the therapeutic effects of MSC treatment, rats were subjected to 7 minutes of transient GCI and treated with MSCs immediately after reperfusion. Hippocampal neuronal death was evaluated at 7 days after ischemia using Fluoro-Jade B (FJB). BBB disruption, endothelial damage, and neutrophil infiltration were evaluated at 7 days after ischemia by immunostaining for IgG leakage, Rat endothelial antigen-1, and myeloperoxidase (MPO). Rats treated with MSCs showed a significantly reduced FJB+ neuron count compared with the control group. They also showed reduced IgG leakage, endothelial damage, and MPO+ cell counts. The present study demonstrated that administration of MSCs after transient GCI provides a dramatic protective effect against hippocampal neuronal death. We hypothesized that the neuroprotective effects of MSC treatment might be associated with the prevention of BBB disruption and endothelial damage and a decrease in neutrophil infiltration.
authors.affiliation: Departments of Emergency Medicine and Surgery, CHA University School of Medicine, Gyeonggi-Do, Republic of Korea; Department of Emergency Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Physiology, Hallym University College of Medicine, Chuncheon, Republic of Korea.
authors.forename: Tae Nyoung
authors.initials: TN
authors.lastname: Chung
authors.affiliation: Departments of Emergency Medicine and Surgery, CHA University School of Medicine, Gyeonggi-Do, Republic of Korea; Department of Emergency Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Physiology, Hallym University College of Medicine, Chuncheon, Republic of Korea.
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Departments of Emergency Medicine and Surgery, CHA University School of Medicine, Gyeonggi-Do, Republic of Korea; Department of Emergency Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Physiology, Hallym University College of Medicine, Chuncheon, Republic of Korea.
authors.forename: Bo Young
authors.initials: BY
authors.lastname: Choi
authors.affiliation: Departments of Emergency Medicine and Surgery, CHA University School of Medicine, Gyeonggi-Do, Republic of Korea; Department of Emergency Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Physiology, Hallym University College of Medicine, Chuncheon, Republic of Korea.
authors.forename: Sung Phil
authors.initials: SP
authors.lastname: Chung
authors.affiliation: Departments of Emergency Medicine and Surgery, CHA University School of Medicine, Gyeonggi-Do, Republic of Korea; Department of Emergency Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Physiology, Hallym University College of Medicine, Chuncheon, Republic of Korea swsuh@hallym.ac.kr wizard95@cha.ac.kr.
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Kwon
authors.affiliation: Departments of Emergency Medicine and Surgery, CHA University School of Medicine, Gyeonggi-Do, Republic of Korea; Department of Emergency Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Physiology, Hallym University College of Medicine, Chuncheon, Republic of Korea swsuh@hallym.ac.kr wizard95@cha.ac.kr.
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Suh
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D016923:Cell Death; D004730:Endothelium, Vascular / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D005260:Female; D064593:Heterografts; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
keywords: Blood-brain barrier; Mesenchymal stem cell; Microglia activation; Myeloperoxidase; Rat endothelial antigen-1; Transient global cerebral ischemia