Postmortem degradation of N-acetyl aspartate and N-acetyl aspartylglutamate: An HPLC analysis of different rat CNS regions

N-acetyl aspartate (NAA), a putative marker of neuronal injury, can be meas ured non-invasively in patients by magnetic resonance spectroscopy (MRS). I nterpretation of in vivo MRS data, however, requires neuropathological corr elates to NAA alterations using autopsy or biopsy material. Since detailed hydrolysis data is lacking, NAA and the related dipeptide N-acetyl aspartyl glutamate (NAAG) were quantified by high performance liquid chromatography (HPLC) in different rat CNS regions over 24 h postmortem. Both molecules de creased rapidly 1-4 h postmortem, and subsequently slower with time. The av erage reduction at 24 h was 46% and 38% for NAA and NAAG respectively. The NAA reduction was proportionally smaller in cortical areas (34-37%) compare d to more caudal regions (54-58%). An exception was the optic nerve, a pure white matter tract, where NAA and NAAG hydrolysis was slower. The NAA/NAAG ratio remained relatively constant, but exhibited marked regional differen ces. The data show a significant postmortem degradation of NAA and NAAG tha t needs to be considered when these compounds are studied ex-vivo.