Relation between delayed impairment of cerebral energy metabolism and infarction following transient focal hypoxia-ischaemia in the developing brain
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Phosphorus magnetic resonance spectroscopy (31P MRS) was used to determined whether focal cerebral injury caused by unilateral carotid artery occlusion and graded hypoxia in developing rats led to a delayed impairment of cerebral energy metabolism and whether the impairment was related to the magnitude of cerebral infarction. Forty-two 14-day-old Wistar rats were subjected to right carotid artery ligation, followed by 8% oxygen for 90 min. Using a 7T MRS system,31P brain spectra were collected during the period from before until 48 h after hypoxia-ischaemia. Twenty-eight control animals were studied similarly. In controls, the ratio of the concentration of phosphocreatine ([PCr]) to inorganic orthophosphate ([Pi]) was 1.75 (SD 0.34) and nucleotide triphosphate (NTP) to total exchangeable phosphate pool (EPP) was 0.20 (SD 0.04): both remained constant. In animals subjected to hypoxia-ischaemia, [PCr] to [Pi] and [NTP] to [EPP] were lower in the 0- to 3-h period immediately following the insult: 0.87 (0.48) and 0.13 (0.04), respectively. Values then returned to baseline level, but subsequently declined again: [PCr] to [Pi] at −0.02 h−1 (P<0.0001). [PCr] to [Pi] attained a minimum of 1.00 (0.33) and [NTP] to [EPP] a minimum of 0.14 (0.05) at 30–40 h. Both ratios returned towards baseline between 40 and 48 h. The late declines in high-energy phosphates were not associated with a fall in pHi. There was a significant relation between the extent of the delayed impairment of energy metabolism and the magnitude of the cerebral infarction (P<0.001). Transient focal hypoxia-ischaemia in the 14-day-old rat thus leads to a biphasic disruption of cerebral energy metabolism, with a period of recovery after the insult being followed by a secondary impaiment some hours later.
Key wordsHypoxia-ischaemia Magnetic resonance spectroscopy Cerebral energy metabolism Newborns Rat
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- Cady EB, Roth SC, Azzopardi D, Aldridge R, Delpy DT, Wylezinska M, Reynolds EOR (1992) Delayed onset intracellular alkalosis and outcome following birth asphyxia (abstract). Proceedings of the Society of Magnetic Resonance in Medicine, 11th annual meeting, Berlin, 2011Google Scholar
- Glantz SA, Slinker BK (1990) Primer of applied regression and analysis of variance. McGraw-Hill, New YorkGoogle Scholar
- Lorek A, Takei Y, Cady EB, Wyatt JS, Penrice J, Edwards AD, Peebles DM, Wylezinska M, Owen-Rees H, Kirkbride V, Cooper C, Aldridge RF, Roth SC, Brown G, Delpy DT, Reynolds EOR (1994) Delayed (“secondary”) cerebral energy failure following acute hypoxia-ischaemia in the newborn piglet: continuous 48-hour studies by31P magnetic resonance spectroscopy. Pediatr Res 36: 699–706PubMedGoogle Scholar
- Roth SC, Azzopardi D, Aldridge R, Cady E, Edwards AD, McCormick DC, Thornton J, Wylezinska M, Wyatt JS, Delpy DT, Reynolds EOR (1991) Progression of changes in cerebral energy metabolism in newborn infants studied by31P magnetic resonance spectroscopy following birth asphyxia (abstract). Neuropediatric 22: 169Google Scholar
- Roth SC, Edwards AD, Cady EB, Delpy DT, Wyatt JS, Azzopardi D, Baudin J, Townsend J, Stewart AL, Reynolds EOR (1992) Relation between cerebral oxidative metabolism following birth asphyxia and neurodevelopmental outcome and brain growth at one year. Dev Med Child Neurol 34: 285–295PubMedCrossRefGoogle Scholar
- Sherwood NM, Timiras PS (1970) A Stereotaxic Atlas of the Developing Rat Brain. Univeristy of California Press, Berkley and Los Angeles, California, pp 110–115Google Scholar