Antagonistic effect of nerve growth factor on neuronal injury induced by hypoxia in cultured cerebral cortical neurons of rats.
OBJECTIVE
To observe the effects of nerve growth factor (NGF) on neuronal hypoxic injury induced by sodium dithionite in primary cultures from gestation of 17-d rat fetal cerebral cortex.


METHODS
Neuronal death and lactate dehydrogenase (LDH) efflux in the bathing medium were measured. The homogenate of cortical cells was used to determine malonyldialdehyde (MDA) content and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities.


RESULTS
When cultures were incubated for 24 h with sodium dithionite, efflux of LDH and MDA content increased while the number of surviving neurons decreased. NGF 100 micrograms.L-1 increased the number of surviving neurons to 85% +/- 9% of normoxia level under hypoxia. NGF 1-100 micrograms.L-1 concentration-dependently attenuated hypoxia-induced increase of efflux of LDH and MDA content, with IC50 of 27 and 49 (95% confidence limits: 18-49 and 29-110) micrograms.L-1. NGF 30 micrograms.L-1 induced a 3-fold increase in SOD and GSH-Px activities. The levels of SOD and GSH-Px activities in hypoxia group were increased 2.7-fold by NGF 100 micrograms.L-1.


CONCLUSIONS
NGF prevented hypoxic insults in cultured cerebral cortical neurons by suppressing the generation of lipid peroxides and increasing the activities of antioxidant enzymes.
Wu
J F
JF
Department of Pharmacology, Chinese Academy of Medical Sciences, Beijing, China.
Zhang
J T
JT
D000818:Animals; D015687:Cell Hypoxia; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D005333:Fetus; D005979:Glutathione Peroxidase / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism*
D009414:Nerve Growth Factors; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase