title: Neuroprotective effects of oligodendrocyte progenitor cell transplantation in premature rat brain following hypoxic-ischemic injury.
abstract: Periventricular leukomalacia (PVL) is a common ischemic brain injury in premature infants for which there is no effective treatment. The objective of this study was to determine whether transplanted mouse oligodendrocyte progenitor cells (OPCs) have neuroprotective effects in a rat model of PVL. Hypoxia-ischemia (HI) was induced in 3-day-old rat pups by left carotid artery ligation, followed by exposure to 6% oxygen for 2.5 h. Animals were assigned to OPC transplantation or sham control groups and injected with OPCs or PBS, respectively, and sacrificed up to 6 weeks later for immunohistochemical analysis to investigate the survival and differentiation of transplanted OPCs. Apoptosis was evaluated by double immunolabeling of brain sections for caspase-3 and neuronal nuclei (NeuN), while proliferation was assessed using a combination of anti-Nestin and -bromodeoxyuridine antibodies. The expression of brain-derived neurotrophic factor (BDNF) and Bcl-2 was examined 7 days after OPC transplantation. The Morris water maze was used to test spatial learning and memory. The results showed that transplanted OPCs survived and formed a myelin sheath, and stimulated BDNF and Bcl-2 expression and the proliferation of neural stem cells (NSC), while inhibiting HI-induced neuronal apoptosis relative to control animals. Moreover, deficits in spatial learning and memory resulting from HI were improved by OPC transplantation. These results demonstrate an important neuroprotective role for OPCs that can potentially be exploited in cell-based therapeutic approaches to minimize HI-induced brain injury.
authors: Key Laboratory of Birth Defect, Children's Hospital of Fudan University, Shanghai, China; Key Laboratory of Neonatal Diseases, Ministry of Health, Children's Hospital of Fudan University, Shanghai, China.
authors: Long-Xia
authors: LX
authors: Chen
authors: Department of Neonatology, Children's Hospital of Fudan University, Shanghai, 201102, China; Key Laboratory of Neonatal Diseases, Ministry of Health, Children's Hospital of Fudan University, Shanghai, China.
authors: Si-Min
authors: SM
authors: Ma
authors: Key Laboratory of Neonatal Diseases, Ministry of Health, Children's Hospital of Fudan University, Shanghai, China.
authors: Peng
authors: P
authors: Zhang
authors: Key Laboratory of Birth Defect, Children's Hospital of Fudan University, Shanghai, China.
authors: Zi-Chuan
authors: ZC
authors: Fan
authors: Key Laboratory of Neonatal Diseases, Ministry of Health, Children's Hospital of Fudan University, Shanghai, China.
authors: Man
authors: M
authors: Xiong
authors: Department of Neonatology, Children's Hospital of Fudan University, Shanghai, 201102, China.
authors: Guo-Qiang
authors: GQ
authors: Cheng
authors: Key Laboratory of Neonatal Diseases, Ministry of Health, Children's Hospital of Fudan University, Shanghai, China.
authors: Yi
authors: Y
authors: Yang
authors: Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
authors: Zi-Long
authors: ZL
authors: Qiu
authors: Department of Neonatology, Children's Hospital of Fudan University, Shanghai, 201102, China; Key Laboratory of Neonatal Diseases, Ministry of Health, Children's Hospital of Fudan University, Shanghai, China.
authors: Wen-Hao
authors: WH
authors: Zhou
authors: Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors: Jin
authors: J
authors: Li
mesh_terms: D064591:Allografts; D000818:Animals; D017209:Apoptosis; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis; D053148:Caspase 3 / Q000096:biosynthesis; D005786:Gene Expression Regulation; D051379:Mice; D058953:Neural Stem Cells / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D009836:Oligodendroglia / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051381:Rats; D033581:Stem Cell Transplantation
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D019253:Proto-Oncogene Proteins c-bcl-2; C505410:Casp3 protein, rat; D053148:Caspase 3