title: Relation between delayed impairment of cerebral energy metabolism and infarction following transient focal hypoxia-ischaemia in the developing brain.
abstract: Phosphorus magnetic resonance spectroscopy (31P MRS) was used to determine 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 impairment some hours later.
authors.affiliation: Department of Paediatrics and Neonatal Medicine, Royal Postgraduate Medical School, London, UK.
authors.forename: R M
authors.initials: RM
authors.lastname: Blumberg
authors.forename: E B
authors.initials: EB
authors.lastname: Cady
authors.forename: J S
authors.initials: JS
authors.lastname: Wigglesworth
authors.forename: J E
authors.initials: JE
authors.lastname: McKenzie
authors.forename: A D
authors.initials: AD
authors.lastname: Edwards
mesh_terms: D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D002544:Cerebral Infarction / Q000378:metabolism* / Q000473:pathology; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D002534:Hypoxia, Brain / Q000378:metabolism* / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors