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Relation between delayed impairment of cerebral energy metabolism and infarction following transient focal hypoxia-ischaemia in the developing brain

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Abstract

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.

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Blumberg, R.M., Cady, E.B., Wigglesworth, J.S. et al. Relation between delayed impairment of cerebral energy metabolism and infarction following transient focal hypoxia-ischaemia in the developing brain. Exp Brain Res 113, 130–137 (1997). https://doi.org/10.1007/BF02454148

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