Distribution of pH changes in mouse neonatal hypoxic-ischaemic insult

Giles S Kendall, Mariya Hristova, Virginia Zbarsky, Amanda Clements, Donald M Peebles, Nicola J Robertson, Gennadij Raivich

Research output: Contribution to journalArticlepeer-review

Abstract

We assessed the distribution in brain pH after neonatal hypoxic-ischaemic insult and its correlation with local injury. Postnatal day 7 mice were injected with neutral red and underwent left carotid occlusion and exposure to 8% oxygen. Images captured from the cut surface of snap-frozen brain were used to calculate the pH from the blue-green absorbance ratios. Carotid occlusion alone had no effect, but combined with hypoxia caused rapid, biphasic pH decline, with the first plateau at 15-30 min, and the second at 60-90 min. The ipsilateral dorsal cortex, hippocampus, striatum and thalamus were most affected. Contralateral pH initially showed only 30% of the ipsilateral decline, becoming more acidotic with increasing duration. Systemic blood analysis revealed, compared with hypoxia alone, that combined insult caused a 63% decrease in blood glucose (1.3 ± 0.2 mM), a 2-fold increase in circulating lactate (17.7 ± 2.9 mM), a reduction in CO(2) to 1.9 ± 0.1 kPa and a drop in pH (7.26 ± 0.06). Re-oxygenation resulted in the normalisation of systemic changes, as well as a global alkaline rebound in brain pH at 4-6 h. A topographic comparison of brain injury showed only a partial correlation with pH changes, with the severest injury occurring in the ipsilateral hippocampus and sparing acidic parts of the contralateral cortex.

Original languageEnglish
Pages (from-to)505-18
Number of pages14
JournalDevelopmental neuroscience
Volume33
Issue number6
DOIs
Publication statusPublished - 2011

Keywords

  • Animals
  • Animals, Newborn
  • Brain/physiopathology
  • Female
  • Functional Laterality
  • Hydrogen-Ion Concentration
  • Hypoxia-Ischemia, Brain/blood
  • Immunohistochemistry
  • Mice
  • Mice, Inbred C57BL

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