Neonatal asphyxia can cause serious problems such as cerebral palsy, mental retardation or epilepsy, and thus the detection and monitoring of hypoxic ischemic (H-I) damage to neonatal brain is important in clinical neonatology. 1H MRS is a non-invasive technique which is potentially sensitive to early metabolic changes in vivo. In this experiment, we studied a newborn brain rabbit model using volume localized MRS. Regional changes of lactate, a sensitive marker of anaerobic metabolism and N-acetyl Aspartate (NAA), considered to be representative of neuronal viability, were investigated following H-I injury. Methods and Results Five New Zealand white rabbits up to 2 weeks old were studied in each of the three conditions :H-I, H-only and I-only. Resonances from NAA, choline, and creatine were observed before hypoxia induction, but no lactate signal was detected following carotid artery ligation prior to the induction of hypoxia. The lactate peak rapidly increased on both sides within 30 minutes after hypoxia induction. After 50 mm, more lactate was produced on ischemic side (p<0.05) than non-ischemic side, and lactate disappeared approximately 3 hrs after removal of hypoxic stress. Lactate production was well correlated with the decrease of oxygen saturation measured by pulse oxymeter. In hypoxia only studies, lactate production was observed equally in both hemispheres within 30 mm and decreased more rapidly than H-I experiments after removal of hypoxia. I-only studies showed no lactate signal or change of other resonances throughout the 5 hrs of observation. Discussion These studies demonstrate that localized 1H MRS can detect and monitor metabolic changes in a rabbit model of neonatal asphyxia. Lactate production was quite sensitive and well correlated with decreasing oxygen saturation. Partial ischemic change caused by unilateral carotid artery ligation enhanced lactate production on ischemic side, but it alone did not cause lactate production in the early phase. No significant changes in NAA or other metabolite peaks were observed during this acute phase. Detection of lactate by 1H MRS will be useful to evaluate tissue hypoxia in vivo.
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