Alterations in glutathione and amino acid concentrations after hypoxia-ischemia in the immature rat brain

Hypoxic-ischemic brain injury involves an increased formation of reactive o xygen species. Key factors in the cellular protection against such agents a re the GSH-associated reactions. In the present study we examined alteratio ns in total glutathione and GSSG concentrations in mitochondria-enriched fr actions and tissue homogenates from the cerebral cortex of 7-day-old rats a t 0, 1, 3, 8, 14, 24 and 72 h after hypoxia-ischemia, The concentration of total glutathione was transiently decreased immediately after hypoxia-ische mia in the mitochondrial fraction, but not in the tissue, recovered, and th en decreased both in mitochondrial fraction and homogenate after 14 h, reac hing a minimum at 24 h after hypoxia-ischemia. The level of GSSG was simila r to4% of total glutathione and increased selectively in the mitochondrial fraction immediately after hypoxia-ischemia. The decrease in glutathione ma y be important in the development of cell death via impaired free radical i nactivation and/or redox related changes. The effects of hypoxia-ischemia o n the concentrations of selected amino acids varied. The levels of phosphoe thanolamine, an amine previously reported to be released in ischemia, mirro red the changes in glutathione. GABA concentrations initially increased (0- 3 h) followed by a decrease at 72 h. Glutamine levels increased, whereas gl utamate and aspartate were unchanged up to 24 h after the insult. The resul ts: on total glutathione and GSSG are discussed in relation to changes in m itochondrial respiration and microtubule associated protein-2 (MAP2) which are reported on in accompanying paper [64]. (C) 2000 Elsevier Science B.V. All rights reserved.