Effects of insulin-like growth factor I on hypoxia-induced cellular injuries in cultured rat cerebellar granule neurons

Abstract

The objective of this study was to test whether IGF-I is protective against neuronal cell injuries induced by hypoxia. Cultured rat cerebellar granule neurons were used as the testing model and exposed to physical hypoxia (100% N[subscript 2]) or chemical hypoxia (rotenone). End points for cell injury were quantitated by biochemical assays, MTT reduction and LDH release. The experimental results suggest the physical and chemical hypoxia induce cell injuries in cultured cerebellar granule neurons in the exposure time- and concentration- related manners, respectively. However, both types of hypoxic conditions used in this study did not lead to neuronal cell death. Treatment with IGF-I markedly attenuated hypoxia-induced cellular injuries when administered before (pre-treatment) and during (co-treatment) neuronal exposure to hypoxia. Cytoprotection was less effective when IGF-I was administered after (post-treatment) the hypoxic condition. In addition, IGF-1 also attenuated hypoxia-induced increases in lipid peroxidation. Therefore, it is likely that IGF-I had protective effect against hypoxia-induced neuronal cell injuries which may be mediated, at least party, by reduction of the lipid peroxidation.