TRANSIENT ELEVATION OF INTERSTITIAL N-ACETYLASPARTATE IN REVERSIBLE GLOBAL BRAIN ISCHEMIA

We evaluated the changes of interstitial N-acetylaspartate (NAA) conce ntration ([NAA](e)) in rat striatum by microdialysis following transie nt global ischemia and depolarization. The dialysate NAA concentration ([NAA](d)) values were corrected for the in vivo recovery to obtain [ NAA](e), by the use of [H-3] mannitol in the perfusion fluid. During g lobal ischemia the relative loss (RL) of [H-3] mannitol decreased to 4 0% of preischemic values, reflecting the decrease in extracellular vol ume fraction. During reperfusion RL of [H-3] mannitol quickly normaliz ed. The [NAA](d) doubled during transient ischemia, which, after corre ction for in vivo recovery, corresponds to a fivefold increase in [NAA ](e) (p < 0.05). Reperfusion induced a > 10-fold increase of [NAA](e) (p < 0.01) with subsequent normalization after 45 min. KCI at 100 mM c aused a reversible 50% reduction in RL of [H-3] mannitol and a three t imes increase in [NAA](e) (p < 0.05) but no further increase when norm al perfusate was reintroduced. The mechanisms of NAA release from neur ons are unknown but may involve the activation of unknown channels/car riers-possibly in relation to a volume regulatory response. The presen t study shows that the distribution of NAA in brain is dynamically reg ulated in acute ischemia and suggests that changes of NAA levels could be caused by other means than neuronal loss.