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Metabolite changes in neonatal rat brain during and after cerebral hypoxia-ischemia: a magnetic resonance
K L Malisza1, P Kozlowski, G Ning
1Institute for Biodiagnostics, NRCC, Winnipeg, Manitoba, Canada.
Insights
Infant rat brain imaging reveals that elevated lactate and reduced N-acetyl-aspartate (NAA) during hypoxia-ischemia predict long-term brain damage. Early recovery of these metabolites indicates no lasting harm.
Area of Science:
- Neuroscience
- Biochemistry
- Medical Imaging
Background:
- Cerebral hypoxia-ischemia is a major cause of brain injury in infants.
- Assessing early markers of brain damage is crucial for timely intervention.
- Proton magnetic resonance spectroscopic imaging (1H-MRSI) allows non-invasive measurement of brain metabolites.
Purpose of the Study:
- To investigate the relationship between in vivo cerebral metabolite changes and long-term brain damage in infant rats following hypoxia-ischemia.
- To compare metabolite profiles and outcomes in different age groups of infant rats exposed to hypoxia-ischemia.
Main Methods:
- Infant rats (6- and 7-day-old) were subjected to unilateral cerebral hypoxia-ischemia.
- Proton magnetic resonance spectroscopic imaging was used to measure cerebral lactate and N-acetyl-aspartate (NAA) concentrations before, during, and after the insult.
- Diffusion-weighted and T2-weighted MRI were used to assess infarct volume at 48 hours post-insult.
Main Results:
- In 6-day-old rats (no infarct), lactate increased during hypoxia-ischemia and normalized quickly; NAA levels remained stable.
- In 7-day-old rats (infarct), lactate remained elevated post-hypoxia, and NAA decreased significantly, with persistent changes at 24 and 48 hours.
- Infarct volumes correlated with sustained elevations in lactate and reductions in NAA.
Conclusions:
- In vivo measurements of cerebral lactate and NAA are reliable predictors of irreversible brain damage in infant rats after hypoxia-ischemia.
- Age-dependent differences in metabolite response correlate with the development of long-term brain injury.
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).