Delayed decreases in specific brain mitochondrial electron transfer complex activities and cytochrome concentrations following anoxia/ischemia.
Hyperglycemic, but not normoglycemic cats exposed to anoxia develop neurologic signs following reoxygenation including fasciculations, focal and tonic-clonic seizures and coma after a symptom-free period. These symptomatic hyperglycemic cats may develop brain edema and will show diffuse neuronal injury or brain infarction depending on length of survival. Brain mitochondria isolated from symptomatic but not asymptomatic cats have decreased ADP- and uncoupler-stimulated oxygen consumption rates. Since impaired respiration could result from altered electron transport chain function, we measured cytochrome c, b, and aa3 concentrations and the activities of the five electron transfer complexes in isolated brain mitochondria. In symptomatic cats marked alterations were present in particular in complex IV, cytochrome oxidase, with a 57% reduction in activity and a 45% reduction in prosthetic group (cytochrome aa3) concentrations. Less marked reductions in other segments of the chain included 27% and 41% decreases, respectively, in cytochrome c concentrations and in electron transfer complex II, succinate:ubiquinone oxidoreductase activity. Cytochrome b concentrations and complex I, II and V activities were unchanged. Small but significant decreases in cytochrome aa3 concentrations (18%) and cytochrome oxidase activity (20%) were also present in mitochondria from postanoxic hyperglycemic cats prior to appearance of neurologic signs. These results indicate that delayed decreases in the activities of specific electron transfer complexes are correlated with impaired mitochondrial respiration and neurologic deterioration in postanoxic hyperglycemic cats. However, it is presently unclear if these postanoxic brain mitochondrial alterations are primary or secondary events in the development of brain injury.
Wagner
K R
KR
Medical Research Service, Veterans Administration Medical Center, Cincinnati, OH 45220.
Kleinholz
M
M
Myers
R E
RE
D000818:Animals; D001929:Brain Edema / Q000209:etiology / Q000378:metabolism; D002415:Cats; D003580:Cytochromes / Q000378:metabolism*; D004579:Electron Transport; D006943:Hyperglycemia / Q000150:complications / Q000378:metabolism*; D000860:Hypoxia / Q000150:complications / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D009422:Nervous System Diseases / Q000209:etiology / Q000378:metabolism; D010101:Oxygen Consumption; D012151:Resuscitation
D003580:Cytochromes