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

• Published in: Neuroscience letters 1999-09, Vol.272 (3), p.207-210
• Main Authors: Weih, Markus, Bergk, Alexandra, Isaev, Nikolaj K, Ruscher, Karsten, Megow, Dirk, Riepe, Mathias, Meisel, Andreas, Victorov, IIya V, Dirnagi, Ulrich
• Format: Article
• Language: English
• Subjects: 3-Nitropropionic acid; Animals; Biotransformation - drug effects; Biotransformation - physiology; Brain Ischemia - genetics; Brain Ischemia - pathology; Cell culture; Cerebral Cortex - blood supply; Cerebral Cortex - drug effects; Cerebral Cortex - pathology; Cerebral ischemia; Cerebrovascular Circulation - drug effects; Cerebrovascular Circulation - physiology; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; Enzyme Inhibitors - pharmacology; Hypoxia; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor 1, alpha Subunit; Ischemic Preconditioning; Neurons - drug effects; Neurons - pathology; NF-kappa B - biosynthesis; NF-kappa B - genetics; Nitro Compounds; Nuclear Proteins - biosynthesis; Nuclear Proteins - genetics; Oxidative phosphorylation; Propionates - pharmacology; Rats; Stroke; Succinate Dehydrogenase - antagonists & inhibitors; Succinate Dehydrogenase - metabolism; Transcription factors; Transcription Factors - biosynthesis; Transcription Factors - genetics; Transcription, Genetic
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/S0304-3940(99)00594-7

Sublethal ischemia leads to increased tolerance against subsequent ischemia. We investigated whether tolerance could also be elicited by mild respiratory-chain inhibition (chemical hypoxia) in a rat neuronal-cell enriched culture system. 3-Nitropropionic acid (3-NPA) caused a concentration-dependent inhibition of succinate-dehydrogenase. Two hours preconditioning with 3-NPA 24–48 h before oxygen-glucose deprivation (OGD) reduced neuronal damage morphologically and reduced lactate deydrogenase (LDH) release up to 72% compared to sham-treated sister cultures without 3-NPA. In an attempt to elucidate transcriptional mechanisms, we found no rapid translocation of the hypoxia-sensitive transcription factors N F-KB or hypoxia-inducible factor-I (HIF-I) at 3-NPA concentrations sufficient to trigger tolerance against OGD. In accordance to previous in vivo and brain slice data, we conclude that 3-NPA chemically induces tolerance against oxygen-glucose deprivation in vitro. However, the underlying mechanisms remain elusive.