Chemiluminescence in hypoxic brain--the first report. Correlation between energy metabolism and free radical reaction.

Abstract

SUMMARY The possibility that cerebral ischemia or cerebral hypoxia may initiate a series of free radical reactions in brain tissue lipid constituents was explored by measuring sequential changes in chemiluminescence values and energy metabolism during brain hypoxia in the rat. Brain hypoxia was induced by means of arterial hypoxemia (PaO 2 17-22 mmHg), normocapnia (PaCO 2 28-38 mmHg) and normotension (MABP 100-140 mmHg). To obtain lowered PaO 2 , 4% O 2 -96% N 2 mixed gas was used. Analysis of the chemiluminescence spectra for the purpose of luminous mechanism investigation was again attempted. No peroxidation occurred in the pre-hypoxic state since there were no photon counts. Chemiluminescence began to rise in the hypoxic state and remained at a high value in the post-hypoxic state. Specifically in the hypoxic state, the 3 min period showed 231 ± 35 counts/10 sec-g (n = 5) and the 5 min period showed 154 ± 62 (n = 19) counts/10 sec-g. In the post-hypoxic state, the 5 min period showed 217 ± 79 counts/10 sec-g (n = 9) and the 30 min period showed a decrease similar to the pre-hypoxlc state. The chemiluminescence spectroanaljsis showed five peaks in wavelength at 480 nm, 520-530 nm, 570 nm, 620-640 nm and 680-700 nm. Sequential changes in energy metabolism revealed that hypoxia caused marked brain lactic acidosis, an increase in both ADP and pyruvate, and a fall in glucose. However, all metabolites recovered at 30 min in the post-hypoxic state, which suggests this was reversible brain hypoxia. Sequential changes in chemiluminescence values and energy metabolism imply the occurrence of free radical reaction in the hypoxic and posthypoxic brain. The spectroanalysis reveals the luminous mechanism as follows: 'Ag + 'Ag -» 2 3 O 2 + h/x Stroke Vol 15, No 6, 1984 IN RECENT YEARS THE AUTO-OXIDATION of unsaturated fatty acids has been suggested as one of the primary factors in the acute stage pathology of the ischemic or hypoxic brain.'" 4 It has been difficult to detect the free radical reactions and further uncertainties remain with regard to the correlation between the period during which lipid peroxidation occurs and the energy metabolism of the brain.5 " 9In the present study, we have followed the sequential changes of chemiluminescence and energy metabolism during a period of both induced hypoxia and oxygen resupply by using supratentorial tissue of hypoxic rat brain (PaO 2 , 17-22 mmHg).Chemiluminescence analysis is a new technique in which the propagation or termination of free radical reaction is thought to appear when singlet oxygen has been transmitted to the triplet oxygen.10 " 15 The results obtained using this new technique were found to be in agreement with the free radical reaction as determined simultaneously from the perspective of energy metabolism. Experimental Materials and MethodsFor the purpose of this study, 142 male Wister rats (250-280 g) were used. In the chemiluminescence value study, 9 rats were sacrificed at pre-hypoxia, 5 at hypoxia-3 min, 19 at hypoxia-5 min, 9 at post-hypoxia-5 min, a...

Brain Superoxide Anion Generation during Asphyxia and Reventilation in Newborn Pigs

“…Then, resuscitation with resultant reperfusion and reoxygenation would activate the prostaglandin endoperoxide synthase pathway further with production of prostanoids (24) and generation of oxygen free radicals. Our study doesn't rule out that substantial superoxide anion also could be produced during the asphyxia period, as has been suggested by Imaizumi et al (25). However, based upon an earlier study (24), we believe that most of the superoxide anion is produced during reventilation.…”

Allopurinol administered prior to hepatic ischaemia in the rat prevents chemiluminescence following restoration of circulation

“…14 Germane to this study is the observation that chemiluminescence occurs in brain homogenates obtained from hypoxic rats, a phenomenon considered to result from hypoxia-induced lipeperoxidation. 3 The methodology in the current study is that used by Boveris et al 6 They showed that free radical-induced lipoperoxidation resulting from infusion of ethyl and tbutyl hydroperoxides into the portal vein was accompanied by hepatic light emission. As much as a 30-fold increase in light output was observed; chemiluminescence decreased within 10-15 rain after discontinuing the infusion.…”

Effect of allopurinol on ischemia and reperfusion-induced cerebral injury in spontaneously hypertensive rats.

“…However, there have been many reports which support the postulation that allopurinol may act effectively on ischemia and reperfusion-induced cerebral injury in spontaneously hypertensive rats by inhibiting the free radical formation. Imaizumi et al 16 have suggested the formation of free radical in hypoxic brain as well as post-hypoxic brain. Vitamin E, a radical scavenger, has been reported to suppress the reperfusion-induced cerebral injury in spontaneously hypertensive rats of the same strain as those we used in the present study, suggesting the involvement of free radical in the genesis of cerebral injury.…”