31P NMR spectroscopy of perinatal hypoxic‐ischemic brain damage: A model to evaluate neuroprotective drugs in immature rats

Gerald D. William, Charles Palmer, Rebecca L. Roberts, Daniel F. Heitjan, Michael B. Smith

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Cerebral energy metabolism can be measured non‐invasively in unanesthetized neonatal rats with 31P NMR spectroscopy. Using this technique, serial changes in high energy phosphates were determined from the right cerebral hemispheres of 7 day postnatal rat pups during a hypoxic‐ischemic insult known to produce focal brain injury. During 3 h of hypoxia‐ischemia the concentration of ATP dropped to 33±8% of prehypoxic (baseline) levels, phosphocreatine (PCr)/Pi decreased from 1.5±0.51 to 0.16±0.06, while pH decreased nominally by 0.2 units. After 2.5 h of recovery in air, ATP returned to 75±10% of baseline levels, PCr/Pi rose to 1.1±0.28, and pH returned to its normal value of 7.16±0.06. This model was used to test the efficacy of the adenosine deaminase inhibitor, 2‐deoxycoformycin (DCF) as a potential neuroprotective drug. The data for the drug‐ and saline‐treated populations were analyzed by integrating ATP and Pi/PCr levels over specific time intervals, expressing it relative to baseline levels, and modeling it with cubic splines. Pretreatment with 500 μg/kg DCF shows a small, but statistically significant, preservation of both ATP and phosphorylation potential during hypoxia and initial recovery. Brain water content (edema) at 42 h recovery was apparently associated with both mean ATP and mean Pi/PCr in the last 2 h of hypoxia‐ischemia. When ATP fell below 70% of baseline, brain edema was evident at 42 h of recovery. This methodology is suitable for extension to human infants.

Original languageEnglish (US)
Pages (from-to)145-153
Number of pages9
JournalNMR in Biomedicine
Volume5
Issue number3
DOIs
StatePublished - Jan 1 1992

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Spectroscopy

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