N-Acetylaspartate, a marker of both cellular dysfunction and neuronal loss: its relevance to studies of acute brain injury.
Résumé
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.
Mots clés
2'-Dipyridyl
Acute Disease
Animals
Aspartic Acid
Biological Markers
Brain Chemistry
Brain Edema
Brain Ischemia
Carotid Arteries
Cell Death
Chromatography
High Pressure Liquid
Corpus Striatum
Disease Models
Animal
Enzyme Inhibitors
Guanidines
Injections
Iron Chelating Agents
Microspheres
Nitro Compounds
Oxidative Stress
Premedication
Propionic Acids
Wistar
Spectrophotometry
Succinate Dehydrogenase