title: The Protective Effect of Human Umbilical Cord Blood CD34+ Cells and Estradiol against Focal Cerebral Ischemia in Female Ovariectomized Rat: Cerebral MR Imaging and Immunohistochemical Study.
abstract: Human umbilical cord blood derived CD34+ stem cells are reported to mediate therapeutic effects in stroke animal models. Estrogen was known to protect against ischemic injury. The present study wished to investigate whether the protective effect of CD34+ cells against ischemic injury can be reinforced with complemental estradiol treatment in female ovariectomized rat and its possible mechanism. Experiment 1 was to determine the best optimal timing of CD34+ cell treatment for the neuroprotective effect after 60-min middle cerebral artery occlusion (MCAO). Experiment 2 was to evaluate the adjuvant effect of 17β-estradiol on CD34+ cell neuroprotection after MCAO. Experiment 1 showed intravenous infusion with CD34+ cells before MCAO (pre-treatment) caused less infarction size than those infused after MCAO (post-treatment) on 7T magnetic resonance T2-weighted images. Experiment 2 revealed infarction size was most significantly reduced after CD34+ + estradiol pre-treatment. When compared with no treatment group, CD34+ + estradiol pre-treatment showed significantly less ADC reduction at 2 h and 2 d, less CBF reduction at 2 h and less hyperperfusion at 2 d. The immunoreactivity of c-Fos, c-Jun and GFAP was attenuated, and BDNF showed significant recovery from 2 h to 2 d after MCAO, especially after CD34+ + estradiol pre-treatment. The present study suggests pre-treatment with CD34+ cells with complemental estradiol can be most protective against ischemic injury, which may act through stabilization of cerebral hemodynamics and normalization of the expressions of immediate early genes and BDNF.
authors.affiliation: Female Urology Section, Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital Linkou Medical Center, Taoyuan, Taiwan.|College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Ching-Chung
authors.initials: CC
authors.lastname: Liang
authors.affiliation: Department of Imaging Physics, The University of Texas M.D. Anderson Cancer Center, Unit 1472, 1515 Holcombe Boulevard, Houston, TX, 77030, United States of America.
authors.forename: Ho-Ling
authors.initials: HL
authors.lastname: Liu
authors.affiliation: Female Urology Section, Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital Linkou Medical Center, Taoyuan, Taiwan.|College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Shuenn-Dhy
authors.initials: SD
authors.lastname: Chang
authors.affiliation: Institute of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan.
authors.forename: Sheng-Hsien
authors.initials: SH
authors.lastname: Chen
authors.affiliation: College of Medicine, Chang Gung University, Taoyuan, Taiwan.|Stroke Section, Department of Neurology and Stroke Center, Chang Gung Memorial Hospital Linkou Medical Center, Taoyuan, Taiwan.
authors.forename: Tsong-Hai
authors.initials: TH
authors.lastname: Lee
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D002545:Brain Ischemia / Q000175:diagnosis / Q000209:etiology / Q000473:pathology* / Q000628:therapy; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002540:Cerebral Cortex / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D002560:Cerebrovascular Circulation; D036101:Cord Blood Stem Cell Transplantation; D004195:Disease Models, Animal; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D010052:Ovariectomy; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats
chemical_list: D018952:Antigens, CD34; D019208:Brain-Derived Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein; D016760:Proto-Oncogene Proteins c-fos; D004958:Estradiol; D048031:JNK Mitogen-Activated Protein Kinases