INVESTIGATION INTO THE ROLE OF N-ACETYLASPARTATE IN CEREBRAL OSMOREGULATION

Marked abnormalities of the magnetic resonance intensity of N-acetylas partate (NAA) have been reported in patients with various neurological disorders, but the neurochemical consequences of these alterations ar e difficult to assess because the function of NAA remains speculative. The purpose of this study was to examine whether NAA plays a role in protecting neurons against osmotic stress. Intracerebral microdialysis was used to expose a small region of the rat dorsolateral striatum to an increasingly hyposmotic environment and to measure resulting chang es in NAA extracellular concentrations. NAA changes in the extracellul ar fluid (ECF) were compared with those of the amino acids, in particu lar, taurine, known to be involved in brain osmoregulation. Stepped in creases in cellular hydration produced by hyposmotic perfusion media i nduced a marked increase in ECF NAA, reflecting a redistribution of NA A from intra- to extracellular space. Parallel experiments showed that , of all the extracellular amino acids measured, only taurine markedly increased with hyposmolar perfusion medium, indicating that the ECF N AA increase associated with hyposmotic stress was a specific response and not passive leakage out of the cells, As NAA is predominantly neur onal, it may contribute to the protection of neurons against swelling (i.e., regulatory volume decrease). In conditions with impaired blood- brain barrier and cytotoxic oedema, efflux of intracellular NAA subseq uent to sustained cellular swelling might lead to a reduction in total brain NAA detectable by magnetic resonance spectroscopy. Alternativel y, redistribution of NAA from intra- to extracellular space implies ch anges in its chemical environment that may alter its magnetic resonanc e visibility.