Metabolite changes in neonatal rat brain during and after cerebral hypoxia-ischemia: a magnetic resonance spectroscopic imaging study

Abstract

Cerebral metabolite concentrations were measured in infant rats using proton magnetic resonance spectroscopic imaging. Measurements were made prior to, during and after exposure of rats (6‐ and 7‐day‐old) to unilateral cerebral hypoxia‐ischemia (right carotid artery occlusion +2 h 8% oxygen). Data clustered according to age and outcome—6‐day‐old animals with no infarct and 7‐day‐old animals with infarct. In 6‐day‐old animals, cerebral lactate concentration increased during hypoxia‐ischemia, particularly ipsilateral to the occlusion, and returned to normal soon after the end of hypoxia. There were no major changes in N‐acetyl‐aspartate levels (NAA) in this group and no regions of hyperintensity on T2 or DW weighted images at 24 h. In the 7‐day‐old animals, lactate increased during hypoxia‐ischemia and remained elevated in the first hour after reperfusion. Furthermore, lactate remained at 258 ± 117% and 233 ± 56% of pre‐hypoxic levels, 24 and 48 h post‐hypoxia, respectively. NAA concentrations ipsilateral to the occlusion decreased to 55 ± 14% during hypoxia, recovered early post‐hypoxia and again decreased to 61 ± 25% and 41 ± 28% at 24 and 48 h post‐hypoxia‐ischemia, respectively. The infarct volumes measured by diffusion weighted and T2 weighted MRI at 48 h post‐hypoxia were 152 ± 40 mm3 and 172 ± 35 mm3, respectively. Thus, irreversible damage correlated well with measured in vivo lactate and NAA changes. Those animals in which NAA was unaltered and lactate recovered soon after hypoxia did not show long‐term damage (6‐day‐old animals), whereas those animals in which NAA decreased and lactate remained elevated went on to infarction (7‐day‐old animals). Copyright © 1999 John Wiley & Sons, Ltd.

Perinatal Iron Deficiency Predisposes the Developing Rat Hippocampus to Greater Injury from Mild to Moderate Hypoxia—Ischemia

“…During and immediately after the HI injury, lactate levels are elevated in both cerebral hemispheres, probably due to anaerobic glycolysis secondary to decreased oxygen delivery (Malisza et al, 1999;Payen et al, 1996). In the present study, lactate levels continued to be elevated one week post-HI injury, when perfusion and oxygenation presumably have been restored at the site of injury (Phillis and O'Regan, 2003).…”

“…In the present study, lactate levels continued to be elevated one week post-HI injury, when perfusion and oxygenation presumably have been restored at the site of injury (Phillis and O'Regan, 2003). Such persistent elevation in lactate is postulated to be due to retention in damaged cells, as well as due to metabolic activity in phagocytic cells at the site of injury (Malisza et al, 1999;Schuhmann et al, 2003). In the present study, increased lactate levels were associated with decreased glucose concentrations, potentially suggesting persistent alterations in substrate utilization in the iron-deficient hippocampus subjected to HI injury.…”

MRI in Rodent Models of Brain Disorders

“…MRS studies have been conducted with the aim of looking at the lactate peak, which becomes prominent when anaerobic glycolysis predominates [116,117,123]. Another important aspect is the N-acetyl-aspartate peak that may show a decrease in completed strokes, but may remain normal if the animals still can recover from the ischemic event [124]. Magnetic resonance angiography [125] and perfusion-weighted imaging [57] have been performed and evaluated in several stroke models.…”

Measuring Oxygenation In Vivo with MRS/MRI—From Gas Exchange to the Cell

“…There is extensive literature on this subject (80). The presence of lactate in pediatric disorders reflects poor outcome (106), but again it is not clear to what level there is concurrent hypoxia.…”