title: Mapping of lactate and N-acetyl-L-aspartate predicts infarction during acute focal ischemia: in vivo 1H magnetic resonance spectroscopy in rats.
abstract: The time course, anatomic distribution, and extent of changes in cerebral lactate, N-acetyl-L-aspartate (NAA), and other metabolite levels determined by three-dimensional in vivo 1H magnetic resonance spectroscopy and single-voxel spectral analysis after middle cerebral artery occlusion in rats. Increased lactate was detected in the central ischemic region within 1.3 hours after the onset of permanent occlusion (n = 22) or 0.5 hour after the onset of 1 hour of temporary occlusion and then reperfusion (n = 8). Permanent occlusion resulted in persistent lactate elevation and a 25.4 +/- 4.1% reduction in the NAA peak after 1.3 hours; NAA was almost completely depleted after 24 hours. Results also demonstrated delayed depletion of all other magnetic resonance spectroscopy-visible 1H metabolites, including creatine, choline, and glutamate, after permanent occlusion. After 1 hour of temporary focal ischemia, lactate returned to nearly normal levels within 0.4 hour after the onset of reperfusion; at 72 hours, a recurrent increase in lactate and a new decrease in NAA were observed, suggesting delayed tissue injury. Histological analysis, performed in 10 rats, demonstrated infarcts that corresponded in distribution to regions of NAA depletion at 72 hours. These findings indicate that lactate elevation is a sensitive early marker of ischemia; however, temporary recovery of lactate accumulation after reperfusion did not predict sustained metabolic recovery. In contrast, NAA depletion within 1.3 hours after the onset of ischemia identified central ischemic regions that were destined for infarction. Potential clinical applications include selection and monitoring of therapeutic intervention, as well as prediction of outcome, in patients with acute stroke.
authors: Magnetic Resonance Unit, Department of Veterans Affairs Medical Center, San Francisco, California, USA.
authors: T
authors: T
authors: Higuchi
authors: E J
authors: EJ
authors: Fernandez
authors: A A
authors: AA
authors: Maudsley
authors: H
authors: H
authors: Shimizu
authors: M W
authors: MW
authors: Weiner
authors: P R
authors: PR
authors: Weinstein
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000175:diagnosis* / Q000503:physiopathology; D002544:Cerebral Infarction / Q000175:diagnosis* / Q000503:physiopathology; D007773:Lactates / Q000097:blood*; D019344:Lactic Acid; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D011379:Prognosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000175:diagnosis / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D007773:Lactates; D001224:Aspartic Acid; D019344:Lactic Acid; C000179:N-acetylaspartate