Initiation and propagation of lipid peroxidation in cerebral infarction models. Experimental studies.
The possibility that cerebral ischaemia or cerebral hypoxia may initiate a series of free radical reactions in brain lipid constituents was explored by measuring sequential changes in chemiluminescence (CL) and electron spin resonance (ESR) during hypoxia or ischaemia load. Brain hypoxia was induced by means of arterial hypoxaemia (PaO2 17-22 mmHg), normocapnia (PaCO2 28-38 mmHg) and normotension (MABP 100-140 mmHg). To obtain lowered PaO2, 4% O2-96% N2 mixed gas was used for artificial ventilation. Spin trapping technique was used in ESR measurement and applied to the detection of free radicals generated in the ischaemic brain homogenate of three-vessel occlusion rat model (global highly ischaemic model with basilar artery coagulation and bilateral carotid artery clipping). Chemiluminescence (CL) began to rise in hypoxic or ischaemic loading and indicates high amounts at an early period of post-hypoxic or ischaemic state. The CL spectroanalysis by wavelength showed five peaks at 480 nm, 520-530 nm, 570 nm, 620-640 nm and 680-700 nm in both hypoxic and ischaemic brain. ESR measurement revealed the PBN (phenyl-t-butyl nitrone) trapped radical, which has hyperfine splitting constants of AN = 16.2-16.5 G and AH beta = 3.6-3.8 G in ischaemia model. An analysis of sequential change of PBN adduct intensity shows a peak at 30 min of ischaemic loading and a marked increase in the recirculation period. Preservation of ATP and marked lactic acidosis were seen in the 5 min hypoxic loading, elsewhere depletion of ATP and marked lactic acidosis were seen in the 5 min, 30 min ischaemia.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D003497:Cyclic N-Oxides; D004195:Disease Models, Animal; D004578:Electron Spin Resonance Spectroscopy; D004734:Energy Metabolism; D005609:Free Radicals; D002534:Hypoxia, Brain / Q000378:metabolism*; D008054:Lipid Peroxides / Q000096:biosynthesis*; D008163:Luminescent Measurements; D008297:Male; D009589:Nitrogen Oxides; D051381:Rats; D011919:Rats, Inbred Strains
D003497:Cyclic N-Oxides; D005609:Free Radicals; D008054:Lipid Peroxides; D009589:Nitrogen Oxides; C029217:phenyl-N-tert-butylnitrone