title: Effects of hypothermia on oligodendrocyte precursor cell proliferation, differentiation and maturation following hypoxia ischemia in vivo and in vitro.
abstract: Hypoxic-ischemia (HI) not only causes gray matter injury but also white matter injury, leading to severe neurological deficits and mortality, and only limited therapies exist. The white matter of animal models and human patients with HI-induced brain injury contains increased oligodendrocyte precursor cells (OPCs). However, little OPC can survive and mature to repair the injured white matter. Here, we test the effects of mild hypothermia on OPC proliferation, differentiation and maturation. Animals suffered to left carotid artery ligation followed by 8% oxygen for 2h in 7-day-old rats. They were divided into a hypothermic group (rectal temperature 32-33 °C for 48 h) and a normothermic group (36-37 °C for 48 h), then animals were sacrificed at 3, 7, 14 and 42 days after HI surgery. Our results showed that hypothermia successfully enhanced early OL progenitors (NG2(+)) and its proliferation in the corpus callosum (CC) after HI. Late OL progenitor (O4(+)) accumulation decreased accompanied with increased OL maturation which is detected by myelin basic protein (MBP) and proteolipid protein. (PLP) immunostaining and immunoblotting in hypothermia compared to normothermia. Additionally, using an in vitro hypoxic-ischemia model-oxygen glucose deprivation (OGD), we demonstrated that hypothermia decreased preOL accumulation and promoted OPC differentiation and maturation. Further data indicated that OPC death was significantly suppressed by hypothermia in vitro. The myelinated axons and animal behavior both markedly increased in hypothermic- compared to normothermic-animals after HI. In summary, these data suggest that hypothermia has the effects to protect OPC and to promote OL maturation and myelin repair in hypoxic-ischemic events in the neonatal rat brain. This study proposed new aspects that may contribute to elucidate the mechanism of hypothermic neuroprotection for white matter injury in neonatal rat brain injury.
authors.affiliation: Key Laboratory of Neonatal Diseases, Ministry of Health, Fudan University, 138 Yi Xue Yuan Road, Shanghai 201102, China.
authors.forename: Man
authors.initials: M
authors.lastname: Xiong
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Si-Min
authors.initials: SM
authors.lastname: Ma
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Wen-Hao
authors.initials: WH
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000941:Antigens / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005106:Exploratory Behavior; D005732:Gangliosides / Q000378:metabolism; D005947:Glucose / Q000172:deficiency; D007036:Hypothermia, Induced / Q000379:methods*; D000860:Hypoxia / Q000473:pathology; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D066298:In Vitro Techniques; D046529:Microscopy, Electron, Transmission; D019081:O Antigens / Q000378:metabolism; D009836:Oligodendroglia / Q000502:physiology* / Q000648:ultrastructure; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D045442:Rotarod Performance Test; D013234:Stem Cells / Q000502:physiology* / Q000648:ultrastructure; D013997:Time Factors; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D005732:Gangliosides; D005947:Glucose; D019081:O Antigens; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4; C062875:ganglioside A2B5
keywords: Hypothermia; Hypoxic-ischemia; Immature brain; Maturation; Oligodendrocyte precursor