Effect of nitric oxide synthase inhibitor on a hyperglycemic rat model of reversible focal ischemia: detection of excitatory amino acids release and hydroxyl radical formation.
Brain Res
; 791(1-2): 146-56, 1998 Apr 27.
Article
em En
| MEDLINE
| ID: mdl-9593867
ABSTRACT
The purpose of this study was to investigate the mechanisms by which a nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), is neuroprotective in the hyperglycemic rat model of 2 h of transient middle cerebral artery occlusion followed by 2 h of reperfusion (MCAO/R). The salicylate trapping method was used in conjunction with a microdialysis technique to continuously estimate hydroxyl radical (.OH) formation by measurement of the stable adducts 2,3- and 2,5-dihydroxybenzoic acid (DHBA). Extracellular excitatory amino acids (EAAs) were detected from the same microdialysis samples. Magnetic resonance imaging (MRI) techniques were used to measure neuronal and cerebrovascular injury. The magnitude of EAA release correlated with the levels of the .OH adducts. Treatment with L-NAME (3 mg/kg, i.p.) 1 min before MCAO, and again 1 min before reperfusion, reduced the levels of DHBA by 46. 4% and glutamate by 50.5% in the hyperglycemic rats compared to untreated hyperglycemic controls. MRI indicated that L-NAME reduced the no-reflow zone and the cytotoxic lesion volume to 22.5% and 21. 0%, respectively, that of hyperglycemic controls. Co-treatment with the nitric oxide (NO) donor L-arginine completely eliminated the protective effects of l-NAME with respect to .OH and EAA levels as well as MRI lesion volume. Our data suggest that hyperglycemic MCAO/R results in excessive glutamate excitotoxicity, leading to enhanced generation of .OH via a NO-mediated mechanism, in turn resulting in severe ischemia/reperfusion brain injury.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ataque Isquêmico Transitório
/
Fármacos Neuroprotetores
/
Óxido Nítrico Sintase
/
NG-Nitroarginina Metil Éster
/
Inibidores Enzimáticos
/
Hiperglicemia
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
Idioma:
En
Revista:
Brain Res
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Estados Unidos