Biomaterial Database

Depletion of brain glutathione by buthionine sulfoximine enhances cerebral ischemic injury in rats. 1992

T Mizui, and H Kinouchi, and P H Chan

Department of Neurology, School of Medicine, University of California, San Francisco 94143.

Oxygen free radicals have been implicated in the pathogenesis of brain injury induced by ischemia/reperfusion. We studied the role of endogenous reduced glutathione (GSH) in brain infarction associated with focal cerebral ischemia caused by permanent ligation of the right middle cerebral artery (MCA) and the right common carotid artery (CCA) plus temporary occlusion of the left CCA. GSH levels in the ischemic side of cortex decreased with time after ischemia and preceded cortical infarction estimated by the staining of mitochondrial respiratory enzymes with 2,3,5-triphenyltetrazolium chloride. GSH levels in the contralateral cortex were unchanged through the experimental periods. The extent of decrease of GSH levels and the severity of infarction in the ischemic cortex at 24 h after ischemia depended on the duration of occlusion of the left CCA. Depletion of brain GSH with buthionine sulfoximine, a selective inhibitor for gamma-glutamylcysteine synthetase, exacerbated cortical infarction and edema after ischemia. These results suggest that the endogenous brain GSH is an important determinant in the defense mechanisms against lesion formation after ischemia and support the possible role of oxygen radicals in the pathogenesis of ischemic brain injury.

UI	MeSH Term	Description	Entries
D007276	Injections, Intraventricular	Injections into the cerebral ventricles.	Intraventricular Injections,Injection, Intraventricular,Intraventricular Injection
D008297	Male		Males
D008717	Methionine Sulfoximine		Sulfoximine, Methionine
D011919	Rats, Inbred Strains	Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.	August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D002544	Cerebral Infarction	The formation of an area of NECROSIS in the CEREBRUM caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., INFARCTION, ANTERIOR CEREBRAL ARTERY), and etiology (e.g., embolic infarction).	Anterior Choroidal Artery Infarction,Cerebral Infarct,Infarction, Cerebral,Posterior Choroidal Artery Infarction,Subcortical Infarction,Cerebral Infarction, Left Hemisphere,Cerebral Infarction, Right Hemisphere,Cerebral, Left Hemisphere, Infarction,Cerebral, Right Hemisphere, Infarction,Infarction, Cerebral, Left Hemisphere,Infarction, Cerebral, Right Hemisphere,Infarction, Left Hemisphere, Cerebral,Infarction, Right Hemisphere, Cerebral,Left Hemisphere, Cerebral Infarction,Left Hemisphere, Infarction, Cerebral,Right Hemisphere, Cerebral Infarction,Right Hemisphere, Infarction, Cerebral,Cerebral Infarctions,Cerebral Infarcts,Infarct, Cerebral,Infarction, Subcortical,Infarctions, Cerebral,Infarctions, Subcortical,Infarcts, Cerebral,Subcortical Infarctions
D002545	Brain Ischemia	Localized reduction of blood flow to brain tissue due to arterial obstruction or systemic hypoperfusion. This frequently occurs in conjunction with brain hypoxia (HYPOXIA, BRAIN). Prolonged ischemia is associated with BRAIN INFARCTION.	Cerebral Ischemia,Ischemic Encephalopathy,Encephalopathy, Ischemic,Ischemia, Cerebral,Brain Ischemias,Cerebral Ischemias,Ischemia, Brain,Ischemias, Cerebral,Ischemic Encephalopathies
D005978	Glutathione	A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.	Reduced Glutathione,gamma-L-Glu-L-Cys-Gly,gamma-L-Glutamyl-L-Cysteinylglycine,Glutathione, Reduced,gamma L Glu L Cys Gly,gamma L Glutamyl L Cysteinylglycine
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001205	Ascorbic Acid	A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant.	Vitamin C,Ascorbic Acid, Monosodium Salt,Ferrous Ascorbate,Hybrin,L-Ascorbic Acid,Magnesium Ascorbate,Magnesium Ascorbicum,Magnesium di-L-Ascorbate,Magnorbin,Sodium Ascorbate,Acid, Ascorbic,Acid, L-Ascorbic,Ascorbate, Ferrous,Ascorbate, Magnesium,Ascorbate, Sodium,L Ascorbic Acid,Magnesium di L Ascorbate,di-L-Ascorbate, Magnesium