1. ^*Department of Neuroendocrinology, Novo Nordisk A/S, Maaloer, Denmark
2. ^†Department of Isotope Chemistry, Novo Nordisk A/S, Maaloer, Denmark
3. ^‡Laboratory of Neuropathology, Rigshospitalet, Copenhagen, Denmark
4. ^§Danish Research Center for Magnetic Resonance, Hvidovre Hospital, Hvidovre, Denmark

Correspondence: Thomas Nikolaj Sager, Department of Pharmacology, NeuroSearch A/S, Smedeland 26B, 2600 Glostrup, Denmark.

Received 2 March 1998; Revised 14 May 1998; Accepted 14 May 1998.

Abstract

Brain N-acetylaspartate (NAA) can be quantified by in vivo proton magnetic resonance spectroscopy (¹H-MRS) and is used in clinical settings as a marker of neuronal density. It is, however, uncertain whether the change in brain NAA content in acute stroke is reliably measured by ¹H-MRS and how NAA is distributed within the ischemic area. Rats were exposed to middle cerebral artery occlusion. Preischemic values of [NAA] in striatum were 11 mmol/L by ¹H-MRS and 8 mmol/kg by HPLC. The methods showed a comparable reduction during the 8 hours of ischemia. The interstitial level of [NAA] ([NAA]_e) was determined by microdialysis using [³H]NAA to assess in vivo recovery. After induction of ischemia, [NAA]_e increased linearly from 70 mol/L to a peak level of 2 mmol/L after 2 to 3 hours before declining to 0.7 mmol/L at 7 hours. For comparison, [NAA]_e was measured in striatum during global ischemia, revealing that [NAA]_e increased linearly to 4 mmol/L after 3 hours and this level was maintained for the next 4 h. From the change in in vivo recovery of the interstitial space volume marker [¹⁴C]mannitol, the relative amount of NAA distributed in the interstitial space was calculated to be 0.2% of the total brain NAA during normal conditions and only 2 to 6% during ischemia. It was concluded that the majority of brain NAA is intracellularly located during ischemia despite large increases of interstitial [NAA]. Thus, MR quantification of NAA during acute ischemia reflects primarily changes in intracellular levels of NAA.