Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Original Paper Dev Neurosci 2011;33:505–518 DOI: 10.1159/000333850 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 Centre for Perinatal Brain Protection and Repair, Department of Obstetrics and Gynaecology, University College London, London, UK 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. Copyright © 2012 S. Karger AG, Basel Introduction Under physiological conditions, brain intracellular pH is maintained at around 7.03 [Siesjö et al., 1972; La- Manna, 1996], 0.3–0.4 pH units below that of the extra- cellular compartment. Over 20 years ago an unexpected response to reperfusion in ischaemic brain was observed in an adult rat when, despite marked intracellular acido- sis during ischaemia, the brain pH normalised after 15 min and subsequently increased above the control values [Mabe et al., 1983]. This rebound alkalosis was confirmed using 31 P magnetic resonance spectroscopy, with longer periods of ischaemia associated with an earlier and more prolonged period of alkalosis [Chopp et al., 1990a, b]. Clinical studies of adult stroke demonstrated alkalosis in areas of chronic infarction [Hugg et al., 1992; Levine et al., 1992; Sappey-Marinier et al., 1992], with a significant correlation between alkalosis and poor clinical outcome Key Words Encephalopathy  Hypoxia-ischaemia  Neonate  Neutral red  pH Abstract We assessed the distribution in brain pH after neonatal hy- poxic-ischaemic insult and its correlation with local injury. Postnatal day 7 mice were injected with neutral red and un- derwent 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 absor- bance ratios. Carotid occlusion alone had no effect, but com- bined 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 in- sult caused a 63% decrease in blood glucose (1.3 8 0.2 m M), a 2-fold increase in circulating lactate (17.7 8 2.9 m M), a re- duction in CO 2 to 1.9 8 0.1 kPa and a drop in pH (7.26 8 0.06). Re-oxygenation resulted in the normalisation of systemic changes, as well as a global alkaline rebound in brain pH at Received: October 11, 2010 Accepted after revision: September 26, 2011 Published online: February 9, 2012 Dr. G.S. Kendall Centre for Perinatal Brain Protection and Repair Department of Obstetrics and Gynaecology, University College London 86–96 Chenies Mews, London WC1E 6HX (UK) Tel. +44 207 679 6065, E-Mail g.kendall  @  ucl.ac.uk © 2012 S. Karger AG, Basel 0378–5866/11/0336–0505$38.00/0 Accessible online at: www.karger.com/dne