Interaction between tissue oxygen tension and NADH imaging during synaptic stimulation and hypoxia in rat hippocampal slices.

Published

Journal Article

Oxygen and NADH are essential components in the production of ATP in the CNS. This study examined the dynamic interaction between tissue oxygen tension (pO(2)) and NADH imaging changes within hippocampal tissue slices, during metabolic stresses including hypoxia and synaptic activation. The initiation of abrupt hypoxia (from 95% O(2) to 95% N(2)) caused a rapid decrease in pO(2), onset of hypoxic spreading depression (hsd; at 6.7+/-1.3 mm Hg; n=15), and a monophasic increase in NADH. Provided that reoxygenation was prompt, synaptic responses, pO(2) and NADH levels returned to baseline following hsd. Longer hypoxia caused irreversible neuronal dysfunction, an increase in pO(2) beyond baseline (due to decreased tissue demand), and hyperoxidation of NADH (10+/-2% decrease below baseline; n=7). Synaptic activation in ambient 95% O(2) caused a decrease or 'initial dip' in pO(2) and a biphasic NADH response (oxidation followed by reduction). The oxidizing phase of the NADH response was mitochondrial as it was synchronous with the 'initial' dip in pO(2). Following slow graded reductions in ambient oxygen levels to 8%, four of seven slices developed hsd following synaptic stimulation. The hypoxic threshold for graded oxygen reductions occurred at 7.9+/-5.8 mm Hg O(2) (n=7). Our hypoxic threshold range (6.7-7.9 mm Hg O(2) from abrupt and graded oxygen reduction, respectively) correlates well with reported in vivo values of <12 mm Hg O(2). The major findings of this study include: 1) determination of the critical physiological threshold of pO(2) (based upon hsd), which is a marker of imminent neuronal death if oxygen is not rapidly restored; 2) NADH hyperoxidation and an increase in pO(2) beyond baseline levels following longer periods of hypoxia; and 3) the occurrence of a pO(2) 'dip' during synaptic stimulation, which correlates with the early oxidizing phase of the biphasic NADH response.

Full Text

Duke Authors

Cited Authors

  • Foster, KA; Beaver, CJ; Turner, DA

Published Date

  • 2005

Published In

Volume / Issue

  • 132 / 3

Start / End Page

  • 645 - 657

PubMed ID

  • 15837126

Pubmed Central ID

  • 15837126

International Standard Serial Number (ISSN)

  • 0306-4522

Digital Object Identifier (DOI)

  • 10.1016/j.neuroscience.2005.01.040

Language

  • eng

Conference Location

  • United States