Oxygen seizure latency and peroxynitrite formation in mice lacking neuronal or endothelial nitric oxide synthases

Ivan T. Demchenko, Dmitriy N. Atochin, Albert E. Boso, Joshua Astern, Paul L. Huang, Claude A. Piantadosi

Research output: Contribution to journalArticlepeer-review

58 Citations (Scopus)


Nitric oxide (NO) from endothelial or neuronal NO synthases (eNOS or nNOS) may contribute both to the cerebrovascular responses to oxygen and potentially to the peroxynitrite-mediated toxic effects of hyperbaric oxygen (HBO2) on the central nervous system (CNS O2 toxicity). In mice lacking eNOS or nNOS (-/-), regional cerebral blood flow (rCBF) and 3-nitrotyrosine (3-NT), a biochemical marker for peroxynitrite (ONOO-) formation, were measured in the brain during HBO2 exposure. These variables were then correlated with EEG spiking activity related to CNS O2 toxicity. In wild-type (WT) mice, HBO2 exposure transiently reduced rCBF, but by 60 min rCBF was restored to baseline levels and above, followed by EEG spikes. Mice lacking nNOS also showed initial depression of rCBF followed by hyperemia but the delay in the onset of EEG discharges was greater. In contrast, in eNOS-deficient mice rCBF did not decrease and hyperemia was less pronounced during HBO2. EEG spike latency was longer in eNOS-/- compared to WT or nNOS-/- mice. 3-NT gradually increased in all strains during HBO2 but accumulation was slower in nNOS-/- mice, consistent with less ONOO- production. These results indicate that NOS-deficient mice have different cerebrovascular responses and tolerance to HBO2 depending on which enzyme isoform is affected. The data suggest a key role for eNOS-dependent NO production in cerebral vasoconstriction and in the development of hyperoxic hyperemia preceding O2 seizures, whereas neuronal NO may mediate toxic effects of HBO2 mainly by its reaction with superoxide to generate the stronger oxidant, peroxynitrite.

Original languageEnglish
Pages (from-to)53-56
Number of pages4
JournalNeuroscience Letters
Issue number1
Publication statusPublished - 19 Jun 2003
Externally publishedYes


  • Cerebral blood flow
  • Hyperbaric oxygen
  • Knockout mice
  • Nitric oxide
  • Oxygen seizures
  • Peroxynitrite

ASJC Scopus subject areas

  • Neuroscience(all)

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