Induction of ischemic tolerance in rat cortical neurons by 3-nitropropionic acid: chemical preconditioning

Sublethal ischemia leads to increased tolerance against subsequent ischemia . We investigated whether tolerance could also be elicited by mild respirat ory-chain inhibition (chemical hypoxia) in a rat neuronal-cell enriched cul ture system. 3-Nitropropionic acid (3-NPA) caused a concentration-dependent inhibition of succinate-dehydrogenase. Two hours preconditioning with 3-NP A 24-48 h before oxygen-glucose deprivation (OGD) reduced neuronal damage m orphologically and reduced lactate deydrogenase (LDH) release up to 72% com pared to sham-treated sister cultures without 3-NPA. In an attempt to eluci date transcriptional mechanisms, we found no rapid translocation of the hyp oxia-sensitive transcription factors N F-KB or hypoxia-inducible factor-1 ( HIF-1) at 3-NPA concentrations sufficient to trigger tolerance against OGD. In accordance to previous in vivo and brain slice data, we conclude that 8 -NPA chemically induces tolerance against oxygen-glucose deprivation in vit ro. However, the underlying mechanisms remain elusive. (C) 1999 Elsevier Sc ience Ireland Ltd. All rights reserved.