BRAIN-TISSUE ACIDOSIS - EFFECTS ON THE EXTRACELLULAR CONCENTRATION OFN-ACETYLASPARTATE

N-Acetylaspartate (NAA) is characterized by a high tissue-to-extracell ular concentration ratio under normal conditions and is released from neurons during hyposmotic cell swelling, As cell volume regulation and acid-base homeostasis share common processes, we have examined by mic rodialysis whether the extracellular concentration of NAA is altered b y various acidotic challenges, Twenty-minute perfusion of 50 mM NH4+ t hrough the microdialysis probe progressively lowered dialysate pH by 0 .18, followed by a sudden, additional reduction after NH4+ removal. Th e latter effect indicated extrusion of cellular H+ because it was supp ressed by blockade of Na+/H+ exchange with 5-(N,N-dimethyl) amiloride (1 or 5 mM in perfusion medium). NH4+ increased dialysate levels of NA A and lactate by approximately two- and threefold their initial values , respectively. These data demonstrate that pronounced intracellular a cidosis is associated with NAA efflux, presumably from neurons, Whethe r this effect is linked directly to acid-base homeostasis or is second ary to acidosis-induced cell swelling remains to be clarified. Hyperca pnia and perfusion of acid medium failed to increase dialysate NAA, pr obably because acidosis was not severe enough or the associated cellul ar swelling was not followed by regulatory volume decrease, As cellula r swelling and acidosis are key features of cerebral ischaemia, furthe r investigations into the role of NAA, and the development of sophisti cated magnetic resonance spectroscopic methods capable of resolving in tra-/extracellular NAA redistribution, would be especially relevant to clinical practice.