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Biomedical subjects

R Busto

Publications and source records attributed to R Busto.

At least 181 records · Page 10Linked to original sources
PubMed1985

Postischemic cerebral lipid peroxidation in vitro: modification by dietary vitamin E.

Using an in vitro system, we studied the effect of postischemic reoxygenation on cerebral lipid peroxidation in relation to the dietary intake of vitamin E (VE) in rats. Homogenates prepared from VE-deficient, -normal, and -supplemented brains, which were previously rendered ischemic for 30 min by decapitation, were incubated under air or nitrogen gas for 60 min. The extent of peroxidation in brain tissue was estimated by a thiobarbituric acid (TBA) test and by diene conjugation in total lipid extracts. The brain levels of alpha-tocopherol and of total and free fatty acids (FAs) were also determined. Aerobic incubation increased TBA reactants in all dietary groups; the effect was largest in the VE-deficient group, intermediate in the VE-normal group, and smallest in the VE-supplemented group. In contrast, nitrogen incubation did not alter the basal levels of TBA reactants except for a small rise associated with VE deficiency. Conjugated dienes changed in parallel with TBA reactants. alpha-Tocopherol decreased after aerobic incubation and also, to a lesser degree, after nitrogen incubation in each dietary group. Only in the reoxygenated samples of the VE-deficient group was there a significant fall in total polyunsaturated FAs. The levels of free FAs continuously increased throughout ischemia and subsequent incubation. However, the level of free polyunsaturated FAs was similar after aerobic and nitrogen incubation in each dietary group, and was not affected by VE. Thus, cerebral reoxygenation after ischemia propagates peroxidative reactions within esterified polyunsaturated FAs. The modification by VE of reoxygenation-induced lipid peroxidation suggests free radical mediation.

Aerobiosis↗
PubMed1985

Compression-induced brain edema in rats: effect of dietary vitamin E on membrane damage in the brain.

Vasogenic edema was produced by focal epidural brain compression followed by sudden decompression in rats raised on diets that varied in content of vitamin E. Cerebral content of total fatty acids and vitamin E was assayed at 24 hours postdecompression after a 24-hour period of compression. Levels of all individual fatty acids in the previously compressed brain region were less by 19 to 22% in the vitamin E-deficient group than in sham-operated controls (p less than 0.05); by 4 to 13% in the vitamin E-normal group; and by 0 to 7% in the vitamin E-supplemented group. Brain levels of vitamin E were not altered by compression in any group. By physicochemical interaction with phospholipids, vitamin E may serve to stabilize membranes after this type of brain injury.

Animals↗
PubMed1985

Metabolic alterations in rat somatosensory cortex following unilateral vibrissal removal.

Local cerebral metabolic rates for glucose were studied by [14C]-2-deoxyglucose autoradiography in adult rats following acute and chronic unilateral deafferentation, with particular attention to the barrel field regions of the primary somatosensory cortex. Deafferentation was produced by permanently removing all of the large whiskers (vibrissae) on one side of the face. Data from experimental animals were then compared to data from sham-operated controls at 1, 5, 10, 15, 30, and 60 days after deafferentation. The rate of glucose utilization was maximally depressed at day 1 in the deafferented barrel field. After that, there was a progressive recovery of glucose utilization toward control levels at each subsequent time point. In contrast, glucose utilization in the barrel field associated with the intact set of whiskers increased by day 5 and remained elevated throughout the duration of the experiment. Similar patterns of altered cerebral metabolism were observed following unilateral infraorbital nerve transection. These results demonstrate that interference with normal somatosensory input causes a transient decrease in glucose metabolism of the contralateral cortical barrel-field and, in addition, causes long-term increments in glucose metabolism in the ipsilateral cortical barrel field--a structure not normally influenced by acute manipulation.

Animals↗
PubMed1984

Regional blood flow in compression-induced brain edema in rats: effect of dietary vitamin E.

Regional cerebral blood flow (rCBF) was studied autoradiographically in a murine model of focal epidural brain compression, and the effect of vitamin E administration was investigated. Mean cortical CBF was reduced to 0.48 to 0.50 ml/gm/min following 2 or 24 hours of compression. Early (2 hours) following subsequent decompression, a mixed pattern of hypoperfusion and hyperperfusion was observed. Twenty-four hours later, rCBF heterogeneities were less marked. Comparisons among animal groups raised on vitamin E-supplemented, vitamin E-normal, and vitamin E-deficient diets 2 hours after decompression revealed marked reductions in rCBF in the previously compressed cortex of the last two groups and hyperemia of the underlying hippocampus. The vitamin E-supplemented rats showed increased flow in the previously compressed cortex. In addition, vitamin E supplementation tended to eliminate rCBF gradients between subjacent zones. These data may help explain our previous observations of the beneficial effects of vitamin E on compression-induced brain edema.

Animals↗
PubMed1984

Concurrent measurement of (Na+, K+)-ATPase activity and lipid peroxides in rat brain following reversible global ischemia.

Lipid peroxides, quantitated as lipid conjugated dienes, and (Na+, K+)-ATPase activity were assayed concurrently in brains of control rats and in three groups subjected to 30 min of reversible forebrain ischemia followed by 0, 1, and 4 hr of recirculation. Multiple small samples were taken from lateral, dorsolateral and medial cortex, hippocampus, thalamus and striatum following in situ freezing. (Na+, K+)-ATPase activity was elevated in hippocampus, dorsolateral and lateral cortex (P less than 0.10) and in thalamus (P less than 0.05) following 30 min ischemia. ATPase activity in medial cortex continued to increase during the first 1 hr of recirculation (P less than 0.10). Following 4 hr of recirculation, decreased enzyme activities were observed in all of these regions (lateral cortex and hippocampus, P less than 0.10). No changes in ATPase activity were observed in samples from striatum. Of the regional samples assayed for lipid peroxide content, the incidence of conjugated dienes as a function of recirculation time was 6% (0 hr), 23% (1 hr), and 17% (4 hr). For these samples, plots of normalized ATPase activity vs. tissue conjugated diene concentration revealed that normalized ATPase activity varied with recirculation time, but was independent of the magnitude of the lipid peroxidative process (expressed in terms of tissue conjugated diene concentration). These results suggest that disturbances in membrane structure and function presumed to arise from lipid peroxidation are not responsible for the behavior of the ATPase under the current in vivo conditions.

Animals↗
PubMed1984

Brain lipid peroxidation induced by postischemic reoxygenation in vitro: effect of vitamin E.

The aerobic incubation of brain after a period of ischemia induced lipid peroxidation. The effect was greatest in vitamin E-deficient rats, intermediate in vitamin E-normal rats, and least in animals supplemented with vitamin E. In contrast, nitrogen incubation following ischemia produced a small effect only in the vitamin E-deficient animals. It appears that reoxygenation is required for lipid peroxides to accumulate in the brain. However, a trace of oxygen remaining during extreme ischemic hypoxia may be sufficient to cause slow propagation of free radical reactions when the vitamin E level is low.

Animals↗
PubMed1984

Cerebral endothelial microvilli: formation following global forebrain ischemia.

Scanning electron microscopy (SEM) and morphometric procedures designed to survey large areas of intraparenchymal vasculature disclosed the widespread production of cerebral endothelial microvilli following global ischemia of the rat forebrain. Although these surface projections were present, they were infrequent, in sham-operated controls. As little as ten minutes of ischemia produced endothelial microvilli, which increased progressively in number with longer periods of ischemia. Transmission electron microscopy (TEM) performed on adjacent serial Vibratome sections confirmed these vascular alterations, although TEM sections did not permit an assessment of their numbers. Endothelial microvilli remained prominent in rats with up to four hours of postischemic recirculation. With SEM, these microvilli were sufficiently numerous so as to suggest that they may play a role in the development of the postischemic hypoperfusion documented by regional cerebral blood flow methods in this and other models of global cerebral ischemia.

Animals↗
PubMed1984

Free fatty acids and energy metabolites in ischemic cerebral cortex with noradrenaline depletion.

We tested whether cerebral noradrenaline (NA) may play a central role in mediating the increased production of free fatty acids (FFAs) during cerebral ischemia. Levels of FFAs, cyclic AMP, and NA, as well as ATP, ADP, and AMP, were measured in cerebral cortex during decapitation ischemia in rats 2 weeks after unilateral locus ceruleus lesion. Comparisons were made between the results obtained from the contralateral cortex with normal NA content and the NA-depleted ipsilateral cortex. Although NA depletion was associated with a diminished transient rise of cyclic AMP in response to ischemia, it failed to influence the magnitude of FFA increase or the decline of energy state within the 15-min period of ischemia. A more than twofold increase of total FFAs (sum of palmitic, stearic, oleic, arachidonic, and docosahexaenoic acids) was observed in both hemispheres at 1 min after decapitation, when energy failure became manifest. The increased production of FFAs continued throughout the 15 min of ischemia, with a preferential rise in the levels of stearic and arachidonic acids. There was an inverse correlation between FFA levels and total adenylate pool. The results do not support a major role for NA and cyclic AMP in increasing cortical FFAs during complete ischemia. Instead, they are consistent with the view that impaired oxidative phosphorylation activates deacylating enzymes. Disturbance of reacylation due to energy depletion is probably another factor contributing to the continuous increase of FFAs during prolonged ischemia.

Adenine Nucleotides↗
PubMed1984

Lipid peroxidation in vivo induced by reversible global ischemia in rat brain.

It has been hypothesized that ischemia, followed by reperfusion, facilitates peroxidative free-radical chain processes in brain. To resolve this question, rats were subjected to reversible global ischemia. From coronal sections of brains frozen in situ, small (ca. 2 mg) amounts of tissue were sampled from neocortex, hippocampus, and thalamus of both cerebral hemispheres of four groups of rats exposed to 30 min cerebral ischemia followed by 0, 30, 60, and 240 min of reperfusion, and from a control group subjected to the same operative procedures, except for the induction of ischemia. Heptane-solubilized total lipid extracts from these samples were analyzed spectroscopically in the 190-330 nm range for content of isolated (nonconjugated) double bonds and of conjugated diene structures; the latter are formed from isolated double bonds during peroxidation of unsaturated fatty acids. Spectra derived from tissue regions of rats subjected to ischemia, or ischemia followed by reperfusion, were compared to averaged, region-specific control spectra and were normalized to the original content of isolated double bonds in the peroxidized samples. The resultant difference spectra were analyzed in terms of ratios of conjugated diene concentration to the concentration of isolated double bonds originally at risk in the specific tissue zones considered. The peak representing conjugated diene formation was centered at 238 +/- 1 nm and was usually well resolved when the molar ratio [conjugated diene]/[isolated double bonds], expressed as a percentage [( CD]/[IDB]), was greater than 0.25%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

alpha-Tocopherol and ubiquinones in rat brain subjected to decapitation ischemia.

Levels of alpha-tocopherol (alpha-Toc), reduced ubiquinones (QH2) and oxidized ubiquinones (Q) were assayed in rat forebrain subjected to decapitation ischemia. Post-decapitation levels of alpha-Toc decreased by 16% at 3 min and 20% at 15 min. Increases in Q9H2 (83%) and in Q10H2 (107%) were observed immediately following decapitation; thereafter their levels began to decrease and approached to the pre-ischemic values at 15 min. In contrast, Q9 and Q10 tended to increase continuously during ischemia. The data indicate that complete ischemia results in distinct changes in the cerebral content of lipid-soluble antioxidants. The decrease of alpha-Toc may make the brain prone to peroxidative attack when cerebral tissue is subsequently reoxygenated.

Animals↗
PubMed1983

Compression-induced brain edema: modification by prior depletion and supplementation of vitamin E.

We studied the degree of edema resulting from focal brain compression in rats raised on vitamin E-deficient, -normal, or -supplemented diets. After release of 24 hours of epidural compression, edema developed ipsilaterally and was characterized by extravasation of serum protein, increased water and sodium content, and little change in potassium. The degree of swelling and increase of sodium in the previously compressed area were most pronounced in the vitamin E-deficient group and mildest in the vitamin E-supplemented group. Degradative processes of biomembranes seem to participate in the pathogenesis of brain edema; vitamin E may stabilize membranes by physicochemical interactions between the phytyl side chain and polyunsaturated phospholipids, or vitamin E may disrupt chains of free radical reactions.

Animals↗
PubMed1982

Potentiation of lipid peroxides by ischemia in rat brain.

Post-ischemic changes in energy metabolites and natural antioxidant compounds have been measured in rat brain in vitro concurrent with two different assays for peroxidized lipids. No exogenous free radical initiators were employed. In vitro oxygenation of minced brain preparations for periods of 10 minutes to 4 hours, following 5 minutes of preparatory ischemia, yielded increased levels of lipid conjugated dienes and TBA-reactive material, in contrast to anaerobically incubated preparations. However, either aerobic or anaerobic incubation of brain minces facilitated increased ratios of lactate:pyruvate and glutathione (oxidized):glutathione (reduced), as well as increased total ubiquinone content and loss of alpha-tocopherol. Observation of lipid radical formation in vivo was then attempted using rats given embolic stroke in one hemisphere and left in the post-ischemic condition for times up to 24 hours. Conjugated dienes were found in lipids extracted from the ipsilateral hemisphere but not from the contralateral hemisphere. These observations of conjugated dienes in vivo (formed presumably during post-ischemic reperfusion) and in vitro (facilitated by oxygenation of brain minces), indicate that lipid radical intermediates and associated chain peroxidation processes are potentiated by ischemia and occur during tissue reoxygenation.

Aerobiosis↗
PubMed1982

A simplified in vivo autoradiographic strategy for the determination of regional cerebral blood flow by positron emission tomography: theoretical considerations and validation studies in the rat.

A simplified mathematical model is described for the measurement of regional cerebral blood flow by positron emission tomography in man, based on a modification of the autoradiographic strategy originally developed for experimental animal studies. A modified ramp intravenous infusion of radiolabeled tracer is used; this results in a monotonically increasing curvilinear arterial activity curve that may be accurately described by a polynomial of low degree (= zeta). Integrated cranial activity CB is measured in regions of interest during the latter portion of the tracer infusion period (times T1 to T2). It is shown that (See formula: text) where each of the terms A chi is a readily evaluated function of the blood flow rate constant kappa, the brain:blood partition coefficient for the tracer, the cranial activity integration limits T1 and T2, the coefficients of the polynomial describing the arterial curve, and an iteration factor n that is chosen to yield the desired degree of precision. This relationship permits generation of a table of CB vs. kappa, thus facilitating on-line computer solution for blood flow. This in vivo autoradiographic paradigm was validated in a series of rats by comparing it to the classical autoradiographic strategy developed by Kety and associates. Excellent agreement was demonstrated between blood flow values obtained by the two methods: CBF in vivo = CBF classical X 0.99 - 0.02 (units in ml g-1 min-1; correlation coefficient r = 0.966).

Animals↗
PubMed1982

Norepinephrine regulation of cerebral glycogen utilization during seizures and ischemia.

Norepinephrine (NE) depletion of the cerebral cortex after lesion of the ipsilateral locus ceruleus (LC) causes abnormalities of cerebral oxidative metabolism when the cortex is stimulated to increased energy demand (Harik, S. I., J. C. LaManna, A. I. Light, and M. Rosenthal (1979) Science 206: 69-71; LaManna, J. C., S. I. Harik, A. I. Light, and M. Rosenthal (1981) Brain Res. 204: 87-101). These abnormalities were exhibited as decreased mitochondrial reducing equivalent flow. One possible cause of this would be the decreased availability of oxidative metabolic substrates in the NE-depleted cortex. We therefore investigated the effect of unilateral LC lesion and the resultant depletion of ipsilateral endogenous NE on glycogen and other energy metabolites in the cerebral cortex of rats under three conditions: (1) at "rest," (2) when energy demand is inncreased markedly by seizures, and (3) during total cerebral ischemia. We report no differences in cerebral metabolites between NE-depleted and control hemispheres at "rest." In seizures and ischemia, however, the increase in the level of adenosine 3':5'-monophosphate (cyclic AMP) and the breakdown of glycogen were impaired considerably in the NE-depleted cortex. The data suggest that depletion of central NE impairs cerebral glycogenolysis in response to increased energy demands and ischemia. Such impairment may be mediated via a cyclic AMP-related mechanism.

Animals↗
PubMed1981

A radioisotopic method for the simultaneous quantitation of regional cerebral blood flow and glucose utilization in small dissected samples: validation studies and values in the nitrous oxide-anesthetized rat.

A method is described for the simultaneous determination of the rates of regional cerebral blood flow (rCBF) and regional cerebral glucose utilization (rCMRgl) in 6-7 mg brain samples dissected from multiple areas of interest. The method utilizes [131I]iodoantipyrine ([131I]IAP) to measure rCBF by indicator fractionation, and [14C]2-deoxyglucose to measure rCMRgl. [131I]IAP was synthesized with specific activity exceeding 350 Ci/mmol and radiochemical purity greater than 99.5% by the radioiodination of antipyrine with Na131I. A triple-counting strategy was developed to quantitate 14C activity of the dissected brain samples in the presence of 131I. The factors contributing to the propagated error of the double-label separation strategy were defined and optimal assay parameters were determined. The separation strategy was validated by measuring rCBF simultaneously with both [131I]IAP (x) and [14C]IAP (y) in a series of rats. The equation of the regression line was y = 1.025 x -0.065 (correlation coefficient 0.985), denoting excellent agreement. In another series of 5 normocapnic rats anesthetized with nitrous oxide, rCBF and rCMRgl were measured simultaneously. In individual animals, the rates of rCBF within 14-16 brain areas were closely coupled to their respective rates of glucose metabolism. For the group data, the linear regression equation relating rCBF (y) to rCMRgl (x) was y = 1.76 x + 0.13 (correlation coefficient 0.93, P less than 0.001). These studies provide direct evidence, based upon data obtained in the same brain, of a close coupling of regional metabolic rate and blood flow.

Animals↗
PubMed1981

The role of hydrostatic pressure in ischemic brain edema.

The mechanisms responsible for early prenecrotic ischemic brain edema were investigated in rats by comparing brain metabolism, tissue water (HOH) content, and sodium and potassium ion concentration in brain during ischemia induced by decapitation, by the Pulsinelli-Brierley technique, and by carotid embolization. Although brain metabolic functions were similarly disturbed in all three groups, an increase in brain HOH occurred only in the embolism model, which allowed collateral perfusion. Early ischemic brain edema is therefore dependent upon (1) impaired energy-dependent ion pumps and (2) a hydrostatic pressure gradient from patient vascular lumens. Elevated perfusion pressure increases the extent of this early edema. Induced hypertension causes impairment of blood-brain barrier function, as evidenced by extravasation of Evans blue dye 5 minutes after embolic ischemia, and strikingly increases the extent of macromolecular extravasation 4 hours after ictus. This increased protein leakage is accompanied by elevated HOH content and sodium concentration, as compared to findings in normotensive animals. It is concluded that the use of induced hypertension as a therapeutic modality in patients with acute stroke may be harmful.

Animals↗