Transient elevation of interstitial N-acetylaspartate in reversible global brain ischemia.
We evaluated the changes of interstitial N-acetylaspartate (NAA) concentration ([NAA]e) in rat striatum by microdialysis following transient 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 [3H]mannitol in the perfusion fluid. During global ischemia the relative loss (RL) of [3H]mannitol decreased to 40% of preischemic values, reflecting the decrease in extracellular volume fraction. During reperfusion RL of [3H]mannitol quickly normalized. The [NAA]d doubled during transient ischemia, which, after correction 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. KCl at 100 microM caused a reversible 50% reduction in RL of [3H]mannitol and a three times increase in [NAA]e (p < 0.05) but no further increase when normal perfusate was reintroduced. The mechanisms of NAA release from neurons are unknown but may involve the activation of unknown channels/carriers-possibly in relation to a volume regulatory response. The present study shows that the distribution of NAA in brain is dynamically regulated in acute ischemia and suggests that changes of NAA levels could be caused by other means than neuronal loss.
Sager
T N
TN
Health Care Discovery, Department of Neuropharmacology, Novo Nordisk A/S, Måløv, Denmark.
Fink-Jensen
A
A
Hansen
A J
AJ
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D005110:Extracellular Space / Q000737:chemistry; D008297:Male; D008353:Mannitol / Q000493:pharmacokinetics; D008564:Membrane Potentials / Q000187:drug effects; D017551:Microdialysis; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism*; D013997:Time Factors; D014316:Tritium
D014316:Tritium; D001224:Aspartic Acid; D008353:Mannitol; C000179:N-acetylaspartate; D011188:Potassium; D002118:Calcium