N-Acetylaspartate, a marker of both cellular dysfunction and neuronal loss: its relevance to studies of acute brain injury.
To evaluate the contribution of cellular dysfunction and neuronal loss to brain N-acetylaspartate (NAA) depletion, NAA was measured in brain tissue by HPLC and UV detection in rats subjected to cerebral injury, associated or not with cell death. When lesion was induced by intracarotid injection of microspheres, the fall in NAA was related to the degree of embolization and to the severity of brain oedema. When striatal lesion was induced by local injection of malonate, the larger the lesion volume, the higher the NAA depletion. However, reduction of brain oedema and striatal lesion by treatment with the lipophilic iron chelator dipyridyl (20 mg/kg, 1 h before and every 8 h after embolization) and the inducible nitric oxide synthase inhibitor aminoguanidine (100 mg/kg given 1 h before malonate and then every 9 h), respectively, failed to ameliorate the fall in NAA. Moreover, after systemic administration of 3-nitropropionic acid, a marked reversible fall in NAA striatal content was observed despite the lack of tissue necrosis. Overall results show that cellular dysfunction can cause higher reductions in NAA level than neuronal loss, thus making of NAA quantification a potential tool for visualizing the penumbra area in stroke patients.
Demougeot
C
C
Unité de Biochimie-Pharmacologie-Toxicologie, Laboratoire de Pharmacodynamie, Faculté de Pharmacie, Dijon, France Service de Neurologie, Centre Hospitalier Universitaire, Dijon, France.
Garnier
P
P
Mossiat
C
C
Bertrand
N
N
Giroud
M
M
Beley
A
A
Marie
C
C
D015082:2,2'-Dipyridyl / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000208:Acute Disease; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000032:analysis*; D015415:Biomarkers; D001923:Brain Chemistry; D001929:Brain Edema / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D002339:Carotid Arteries; D016923:Cell Death; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D007269:Injections, Intra-Arterial; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008314:Malonates / Q000633:toxicity; D008863:Microspheres; D008928:Mitochondria / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009574:Nitro Compounds; D018384:Oxidative Stress; D011292:Premedication; D011422:Propionates / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013056:Spectrophotometry, Ultraviolet; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors
D015415:Biomarkers; D004791:Enzyme Inhibitors; D006146:Guanidines; D007502:Iron Chelating Agents; D008314:Malonates; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D009574:Nitro Compounds; D011422:Propionates; D001224:Aspartic Acid; D009569:Nitric Oxide; D015082:2,2'-Dipyridyl; C000179:N-acetylaspartate; C030290:malonic acid; D019001:Nitric Oxide Synthase; D013385:Succinate Dehydrogenase; C015392:3-nitropropionic acid; C004479:pimagedine