A COMPARATIVE-STUDY OF ETHANOL, HYPOGLYCEMIA, HYPOXIA AND NEUROTROPHIC FACTOR INTERACTIONS WITH FETAL-RAT HIPPOCAMPAL-NEURONS - A MULTIFACTOR IN-VITRO MODEL FOR DEVELOPMENTAL ETHANOL EFFECTS

Fetal alcohol syndrome (FAS) is characterized by numerous central nerv ous system anomalies, with the hippocampus being particularly vulnerab le to developmental ethanol exposure. In addition to direct ethanol ne urotoxicity, other conditions resulting from maternal ethanol consumpt ion, such as hypoglycemia and hypoxia, may also contribute to FAS. The present study used a tissue culture system to model multiple conditio ns which may relate to in vivo FAS, and assessed their relative neurot oxicity with MTT assays. Gestational day 18 rat hippocampal cultures w ere exposed to varying ethanol concentrations, glucose withdrawal-indu ced hypoglycemic (gwHG, 16 h) or acute hypoxic (aHP, 2 h) conditions a lone, as well as to co-treatments with ethanol and gwHG or aHP. Brain- derived neurotrophic factor (BDNF) and nerve growth factor (NGF) have previously been shown to ameliorate ethanol-, hypoglycemia-and hypoxia -induced neurotoxicity. Therefore, their neuroprotective potential, al ong with ciliary neurotrophic factor (CNTF), was examined. Neuronal vi ability was reduced dose-dependently by ethanol, alone or with hypogly cemia or hypoxia. Ethanol + gwHG or aHP was not uniformly additive. NG F treatment provided the most extensive neuroprotection, being effecti ve against ethanol (200 and 400 mg/dl), gwHG, and aHP, alone and combi ned. BDNF afforded similar protection, but not against ethanol + gwHG. CNTF protected only against aHP. CNTF + BDNF, previously shown to act synergistically, protected against ethanol + aHP up to 800 mg/dl etha nol, but not, paradoxically, against ethanol alone, gwHG, or ethanol gwHG, all conditions BDNF alone protected against. This study demonst rated that several neurotrophic factors are capable of mitigating neur otoxicity associated with ethanol, hypoglycemia and hypoxia. (C) 1998 Elsevier Science B.V.