IGF-1 protects oligodendrocyte progenitor cells and improves neurological functions following cerebral hypoxia-ischemia in the neonatal rat.
To investigate if insulin-like growth factor-1 (IGF-1) provides neuroprotection to oligodendrocyte progenitor cells (OPCs) following cerebral hypoxia-ischemia, a previously developed neonatal rat model of white matter damage was used in this study. Postnatal day 4 (P4) SD rat pups were subjected to bilateral common carotid artery ligation, followed by exposure to 8% oxygen for 10 min. IGF-1 (0.5 microg) or vehicle was injected into the left ventricle after artery ligation and before the hypoxic exposure. Cerebral hypoxia-ischemia caused death of O4+ late OPCs in the P5 rat brain and impaired myelination in the P9 and P21 rat brain. Caspase-3 activation was involved in the death of OPCs. Moreover, cerebral hypoxia-ischemia impaired neurobehavioral performance in juvenile rats. IGF-1 treatment attenuated damages to OPCs and improved neurological functions after cerebral hypoxia-ischemia. It reduced death of O4+ OPCs by 39% on P5 and enhanced myelination on P9 and P21. Bromodeoxyuridine uptake assay showed that cerebral hypoxia-ischemia inhibited proliferation of stem/progenitor cells in the subventricular zone and NG2+ early OPCs in the white matter area. IGF-1 treatment increased cell proliferation in the subventricular zone by 31% 1 day following hypoxic-ischemic insult. Proliferation of early and late OPCs in the IGF-1-treated group was 1.5- and 2.4-fold of that in the vehicle-treated group, respectively. In conclusion, IGF-1 provided potent neuroprotection to OPCs and improved neurological functions following cerebral hypoxia-ischemia in the neonatal rat. The neuroprotection of IGF-1 was associated with its antiapoptotic and mitogenic effects.
Lin
Shuying
S
Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Fan
Lir-Wan
LW
Pang
Yi
Y
Rhodes
Philip G
PG
Mitchell
Helen J
HJ
Cai
Zhengwei
Z
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism*; D007276:Injections, Intraventricular; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology
D018696:Neuroprotective Agents; D007334:Insulin-Like Growth Factor I