N-acetylaspartate distribution in rat brain striatum during acute brain ischemia

Brain N-acetylaspartate (NAA) can be quantified by in vivo proton magnetic resonance spectroscopy (H-1-MRS) and is used in clinical settings as a mark er of neuronal density. It is, however, uncertain whether the change in bra in NAA content in acute stroke is reliably measured by H-1-MRS and how NAA is distributed within the ischemic area. Rats were exposed to middle cerebr al artery occlusion. Preischemic values of [NAA] in striatum were 11 mmol/L by H-1-MRS and 8 mmol/kg by HPLC. The methods showed a comparable reductio n during the 8 hours of ischemia. The interstitial level of [NAA] ([NAA](e) ) was determined by microdialysis using [H-3]NAA to assess in vivo recovery . After induction of ischemia, [NAA](e) increased linearly from 70 mu mol/L to a peak level of 2 mmol/L after 2 to 3 hours before declining to 0.7 mmo l/L at 7 hours. For comparison, [NAA](e) was measured in striatum during gl obal 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 [C-14]mannitol, t he relative amount of NAA distributed in the interstitial space was calcula ted to be 0.2% of the total brain NAA during normal conditions and only 2 t o 6% during ischemia. It was concluded that the majority of brain NAA is in tracellularly located during ischemia despite large increases of interstiti al [NAA]. Thus, MR quantification of NAA during acute ischemia reflects pri marily changes in intracellular levels of NAA.