INCREASE OF HYPOXIC TOLERANCE IN RAT HIPPOCAMPAL SLICES FOLLOWING 3-NITROPROPIONIC ACID IS NOT MEDIATED BY ENDOGENOUS NERVE GROWTH-FACTOR

Chemical preconditioning with low dose inhibition of succinic dehydrog enase by 3-nitropropionic acid (3-np) increases tolerance against succ eeding hypoxia. Supraphysiological doses of nerve growth factor (NGF) repeatedly were shown to protect against ischemic damage. We investiga ted whether increased tolerance against hypoxia results from increased or accelerated production of endogenous NGF. Average recovery of popu lation spike amplitude after 15 min of hypoxia and 45 min of reoxygena tion was 31 +/- 9% (mean +/- SE) in control hippocampal slices. After pretreatment with 3-np (single i.p. injection of 20 mg/kg body weight 1 h to 3 days prior to slice preparation), recovery exceeded 90% (P < 0.01). However, NGF content did not increase upon slice preparation, h ypoxia in vitro, and pretreatment with 3-np in vivo 1 h to 1 day prior to slice preparation with and without additional hypoxia in vitro. We conclude that early-onset tolerance to hypoxia induced by 3-np treatm ent is not caused by induction of endogenous NGF production.