Brain respiratory activity

The brain has a number of characteristics that make it especially susceptible to free- radical-mediated injury. Brain lipids are highly enriched in polyunsaturated fatty acids and many regions of the brain, for example, the substantia nigra and the striatum, have high concentrations of iron. Both these factors increase the susceptibility of brain cell membranes to lipid peroxidation. Because the brain is critically dependent on aerobic metabolism, mitochondrial respiratory activity is higher than in many other tissues, increasing the risk of free radical Teak from mitochondria conversely, free radical damage to mitochondria in brain may be tolerated relatively poorly because of this dependence on aerobic metabolism. 

Pettersen JC, Cohen SD. 1993. The effects of cyanide on brain mitochondrial cytochrome oxidase and respiratory activities. J Appl Toxicol 13(1) 9-14. 

The respiratory activity of the brain tissue was determined by measuring the rate of oxygen uptake with a Clark oxygen electrode (7). The sample of tissue (a brain half) was treated exactly as if used in a calcium efflux experiment except no radioactivity or RF power was used. Following this procedure which required about 55 minutes, the tissue was placed in the oxygen electrode cell containing 1.6 ml of the standard medium (pH 7.8) at 37°C and the rate of oxygen uptake was recorded. 

Figure 5. Respiratory activity of chick brain tissue.

Respiratory Activity of Brain. Questions concerning the metabolic state of the isolated brain tissue are frequently posed. Figure 5 shows the respiratory activity of a brain half which had undergone the same treatment as a sample used in calcium efflux experiments. The initial linear portion of the curve represents a respiratory rate of about 100 ng atoms oxygen/min. The rate decreased with time and more than 90% of the oxygen in the medium was depleted in less than 10 min. 

When the oxygen-depleted solution was repeatedly replaced with fresh medium, very similar curves were obtained. For example, the initial respiratory rates in the second and third replacement volumes were 6% and 15% less than the first trial, respectively. The tissue was therefore capable of respiratory activity throughout the 55 to 60 minute experimental period. Freshly excised brain samples exhibited similar responses at slightly higher respiratory rates. One should recall that Bawin et al. 

The mitochondrial Mg2+ ATPase activity from liver and brain was inhibited by about 50-60% after an administration of 100 mg Al kg 1 body weight in the diet for a period of 90-120 days. By contrast, in the heart mitochondria, the ATPase activity increased from 73 to 212% after this treatment [38]. In this work, it was also found that ADP phosphorylation rates were decreased by 46% and that the changes in the ATPase activity, in general, were paralleled to those of the respiratory rates. The author suggested that these results imply that the effects of Al3+ treatment on respiratory activity and the ATPase activity go hand in hand. Curiously, liver and brain mitochondria presented doubled aluminum concentration and impaired respiration rate, whereas the heart mitochondria, that accumulated 11 times higher amount of aluminum, presented stimulation of respiration. Thus, an indirect action of aluminum in this tissue could be suggested. 

Copper and Zinc in Aerobic Metabolism. Cytochrome oxidase, the terminal oxidase in the electron transport chain contains an atom of copper. On this enzyme the protons and electrons generated during oxidative metabolism combine with elemental oxygen to form water. During copper deficiency the tissue concentration of cytochrome oxidase is reduced. While the effects of lower cytochrome oxidase activity on exercise has not been described, it is likely that aerobic energy metabolism will be diminished. This effect of copper deficiency was first described in animals with myelin aplasls — the degeneration myelin (86). The oxidative process of phospholipid synthesis, a primary component of myelin, was depressed. Liver mitochondria had impaired respiratory activity (87). Cytochrome oxidase activity was also depressed in brain, heart and liver. 

Ribiere, C., Hininger, I., Saffar-Boccara, C., Sabourault, D., and Nordmann, R. (1994). Mitochondrial respiratory activity and superoxide radical generation in the liver, brain, and heart after chronic ethanol intake. Biochem. Pharmacol. 47 1827-1833. 

B) MAJOR BODILY FUNCTIONS.—For purposes of paragraph (1), a major life activity also includes the operation of a major bodily function, including but not limited to, functions of the immune system, normal cell growth, digestive, bowel, bladder, neurological, brain, respiratory, circulatory, endocrine, and reproductive functions. 

Wasicko MJ, Neubauer JA, Melton JE, Haiangozo AM, Edelman NH. The effect of progressive brain h.3q)oxia on respiratory activity of the hypoglossal nerve. Fed Proc 1987 46 1418. 

Biochemical and Physiological Properties.—2-Arylimino-3-(p-chloro-phenethyl)thiazolidin-4-ones inhibit the oxidation of 2-oxoglutarate, citrate, 3-hydroxybutyrate, and pyruvate, but have no inhibitory effect on the respiratory activity of rat brain homogenate with sodium succinate used as substrate. They thus appear to exert selective inhibition of NAD -dependent oxidations. 

Chemoreceptor response to decreased arterial P02. Hypoxia has a direct depressant effect on central chemoreceptors as well as on the medullary respiratory center. In fact, hypoxia tends to inhibit activity in all regions of the brain. Therefore, the ventilatory response to hypoxemia is elicited only by the peripheral chemoreceptors. 

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