IGF-1 protects oligodendrocyte progenitor cells and improves neurological functions following cerebral hypoxia-ischemia in the neonatal rat.

Abstract

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.

• Authors: Shuying Lin, Lir-Wan Fan, Yi Pang, Philip G Rhodes, Helen J Mitchell, Zhengwei Cai
• Journal: Brain research (Brain Res) Vol. 1063 Issue 1 Pg. 15-26 (Nov 23 2005) ISSN: 0006-8993 [Print] Netherlands
• PMID: 16259966 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Neuroprotective Agents
• Insulin-Like Growth Factor I

Topics

• Animals
• Animals, Newborn
• Brain (cytology, metabolism, pathology)
• Cell Death (physiology)
• Cell Differentiation (physiology)
• Cell Proliferation
• Hypoxia-Ischemia, Brain (metabolism)
• Injections, Intraventricular
• Insulin-Like Growth Factor I (administration & dosage, metabolism)
• Neuroprotective Agents (administration & dosage, metabolism)
• Oligodendroglia (metabolism, pathology)
• Organ Size
• Rats
• Rats, Sprague-Dawley
• Stem Cells (metabolism, pathology)