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 +2h 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).