Application of magnetic resonance imaging to the measurement of neurodegeneration in rat brain: MRI data correlate strongly with histology and enzymatic analysis.
Focal brain ischemia was induced by middle cerebral artery occlusion in the rat. The volume of cerebral damage was determined 2 days later by MRI in vivo and in the same animals histologically. The edema volume as measured by MRI and the histologically determined infarction was highly correlated. As a consequence, the neuroprotective effect of the N-methyl-D-aspartate (NMDA) receptor antagonists CGP 40116 and MK 801 were similar with both methods. Excitotoxic neurodegeneration in the rat striatum was induced by direct injection of quinolinic acid. The degree of damage was evaluated in vivo 1 day later by quantitative MRI, and 7 days later by measuring the activities of neuronal marker enzymes choline acetyltransferase and glutamic acid decarboxylase. Striatal damage assessed using the three approaches was highly correlated. Cerebroprotective efficacy of the NMDA receptor antagonist CGP 40116 was indistinguishable based on all methods. MRI was more reproducible than the enzymatic methods and was faster and simpler than histologic examination for routine analysis of excitotoxic damage and cerebroprotection in vivo in a pharmaceutical research environment.
Biology Research Laboratories, Pharmaceuticals Division, Ciba-Geigy Ltd., Basel, Switzerland.
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Allegrini
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Sauer
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000627:therapeutic use; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000473:pathology*; D002536:Cerebral Arteries / Q000503:physiopathology; D002795:Choline O-Acetyltransferase / Q000032:analysis; D004796:Clinical Enzyme Tests; D003250:Constriction; D016291:Dizocilpine Maleate / Q000627:therapeutic use; D005968:Glutamate Decarboxylase / Q000032:analysis; D002546:Ischemic Attack, Transient / Q000175:diagnosis* / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D008279:Magnetic Resonance Imaging; D009410:Nerve Degeneration / Q000187:drug effects; D017378:Quinolinic Acid; D051381:Rats; D011916:Rats, Inbred F344
C064539:2-amino-4-methyl-5-phosphono-3-pentenoic acid; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase; D017378:Quinolinic Acid