Cerebral hypoxia-ischemia in immature rats: involvement of mitochondrial permeability transition?
The aim of this study was to evaluate the involvement of mitochondrial membrane permeability transition (MPT) after hypoxia-ischemia (HI) in 7-day-old rats. [14C]2-deoxyglucose (DOG) was administered to controls, and at various time points after HI. MPT in the cerebral cortex was measured as entrapment of DOG-6-P in mitochondria. Another group of rats was treated with the MPT inhibitor cyclosporin A (CsA; 10-50 mg/kg i.p.) or vehicle before and after HI, and the effect on brain injury and mitochondrial respiration was evaluated. A significant increase in DOG-6-P entrapment in mitochondria indicated that MPT occurred in two phases: a primary MPT after 0-1.5 h and a secondary MPT after 6.5-8 h of reperfusion. However, CsA did not affect brain injury or mitochondrial respiration. The data suggest that MPT occurred after HI but does not provide evidence for its involvement in the development of injury.
Puka-Sundvall
M
M
Department of Anatomy and Cell Biology, Perinatal Center, Göteborg University, Sweden. Malgorzata.Puka-Sundvall@anatcell.gu.se
Gilland
E
E
Hagberg
H
H
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism; D002250:Carbon Radioisotopes; D016572:Cyclosporine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019298:Glucose-6-Phosphate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D051381:Rats
D002250:Carbon Radioisotopes; D004791:Enzyme Inhibitors; C015785:2-deoxyglucose-6-phosphate; D019298:Glucose-6-Phosphate; D016572:Cyclosporine