ISSN:0736-5748    

DOI:10.1016/0736-5748(91)90001-3

出版商:Wiley    

年代:2003

数据来源: WILEY

摘要:

AbstractAfter spinal cord injury, two groups of cats were treated with a combination of methylprednisolone sodium succinate (MP, 35 mg/kg) and epsilon‐aminocaproic acid (EACA, 350 mg/kg), and guanabenz acetate (0.65 mg/kg). Guanabenz acetate was administered twice daily for 8 weeks. In the first group, the treatment significantly increased blood flow in the abdominal aorta. All cats treated with guanabenz acetate 3 hr after spinal cord contusion had return of micturition and none suffered complete paraplegia. Four animals had partial and the other four had complete motor recovery. A superoxide (O2−) generating system, horseradish peroxidase, decreased [14C]gamma amino butyric acid uptake by mouse cortical slices by 33% but when superoxide dismutase was added to the medium, the uptake was reduced by only 9%. The nerve endings were also protected by superoxide dismutase from morphologic damage by (O2−) as observed by electron microscopy. The agents used in these studies produce their ameliorating effects by virtue of their anti‐inflammatory, antioxidant. and membrane stabilizing properties, and enhancing the regional microcirculation. In addition to having these properties, guanabenz acetate is also an alpha2adrenoceptor agonist.

ISSN:0736-5748    

DOI:10.1016/0736-5748(91)90002-4

出版商:Wiley    

年代:2003

数据来源: WILEY

摘要:

AbstractIt is now becoming increasingly clear that free radicals contribute to brain damage in several conditions, such as hyperoxia and trauma. It has been more difficult to prove that free radical production mediates ischemic brain damage, but it has often been suggested that it may be a major contributor to reperfusion damage, observed following transient ischemia. Recent results demonstrate that cerebral ischemia of long duration, particularly when followed by reperfusion, leads to enhanced production of partially reduced oxygen species, notably hydrogen peroxide (H2O2). It has also been suggested that postischemic hyperoxia, e.g. an increased oxygen tension during the recirculation period, adversely affects recovery following transient ischemia. Other data support the notion that brain damage caused by permanent ischemia (stroke) is significantly influenced by production of free radicals. The present study, however, fails to show that recirculation following brief periods of ischemia (15 min) leads to an enhanced H2O2production, and that hyperoxia aggravates the ischemic damage.This study was undertaken to reveal whether variations in oxygen supply in the postischemic period following forebrain ischemia in rats affect free radical production and the brain damage incurred. To that end, rats ventilated on N2O/O2(70:30) were subjected to 15 min of transient ischemia. Normoxic animals were ventilated with the N2O/O2mixture, hyperoxic animals with 100% O2, and hypoxic ones with about 10% O2(balance either N2O/N2or N2) during the recirculation. At the end of this period, the animals were decapitated for assessment of H2O2production with the aminotriazole/catalase method. This method is based on the notion that aminotriazole interacts with H2O2to inactivate catalase; thus, the rate of inactivation of catalase in aminotriazole treated animals reflects H2O2production. In a parallel series, animals ventilated with one of the three gas mixtures in the early recirculation period, respectively, were allowed to recover for 7 days, with subsequent perfusion‐fixation of brain tissues and light microscopical evaluation of the brain damage.Animals given aminotriazole, whether rendered ischemic or not, showed a reduced tissue catalase activity, reflecting H2O2production in the brain. Hyperoxic animals failed to show increased tissue H2O2production, while hypoxic ones showed a tendency towards decreased production. However, all three groups (hypo, normo‐ and hyperoxic) had similar density and distribution of neuronal damage. These results suggest that although postischemic oxygen tensions may determine the rates of H2O2production, variations in oxygen tensions do not influence the final brain damage incurred.In conclusion, there was thus no indication that variations in the postischemic oxygen supply altered production of free radicals, or modulated the damage incurred as a result of the ischemia. We conclude that free radical production may not be an important factor in the pathogenesis of brain damage following brief periods of ischemia, but may represent an important modulator following longer periods of ischemia, when a vascular component becomes an important factor in the pathological events.

ISSN:0736-5748    

DOI:10.1016/0736-5748(91)90003-5

出版商:Wiley    

年代:2003

数据来源: WILEY

摘要:

AbstractThe relation between cerebral oxygen radicals and the aging process was investigated in crude synaptosomal (P2) fractions from rats. The rate of formation of oxygen radicals was measured using the probe 2′,7′‐dichlorofluorescein diacetate (DCFH‐DA), which is de‐esterified and subsequently oxidized by oxygen radicals to a fluorescent product 2′,7′‐dichlorofluorescein (DCF). There was a significant agedependent decrease in the formation rate of oxygen radicals, observed by decreased formation of DCF. No difference in oxygen radical formation was apparent between age groups following anin vitrochallenge with an ascorbate/FeSO4mixture. This age‐dependent decrease in cerebral oxygen radical generation coincided with age‐dependent increases in Superoxide dismutase. No age‐related alterations in lipid order in either the hydrophilic or lipophilic membrane regions were observed using fluorescence polarization analysis. Age‐dependent losses in cerebral P2 tryptophan fluorescence (a measure of protein degradation), and increased liberation of [14C]protein fragments into the acid‐soluble fraction (a measure of overall proteolytic activity) were observed. Results suggest that aging does not proceed as a result of elevated rates of generation of oxygen radicals, a finding that does not support the proposed free radical theory of aging. The observed age‐dependent decrease in the formation of oxygen radicals does not effect membrane lipid order. These findings implicate modifications in proteins and activated protein catabolic pathways as major contributing factors in the normal physiological process of senescence.

ISSN:0736-5748    

DOI:10.1016/0736-5748(91)90004-6

出版商:Wiley    

年代:2003

数据来源: WILEY

摘要:

AbstractCerebellar granule cells from 5–12‐day‐old rats can be incubated in suspension at 37°C for up to 3 hr with minimal decline in viability. Methyl mercury was found to produce time‐ and concentrationdependent cell killing with>85% cell death after 3 hr exposure to a concentration of 20 μM. Previously characterized inhibition of protein and RNA synthesis as well as known methyl mercury‐induced defects in cellular ATP production have been shown to be incapable of causing this degree of cell death. Here we report that methyl mercury induced a concentration‐dependent increase in membrane lipoperoxidation and a rapid decline in reduced glutathione in this cerebellar neuronal preparation. Hydrogen peroxide at 5 mM was found to closely reproduce each of the cytotoxic effects manifested by methyl mercury suggesting that oxidizing conditions produced by methyl mercury may account for the observed cell death. Methyl mercury‐induced lipoperoxidation was not the cause of cell death since malonaldehyde production could be blocked by α‐tocopherol or EDTA without appreciably protecting against cell death. Significant protection from methyl mercury‐induced cell death was observed, with EGTA, deferoxamine and KCN. We propose that oxidative events contribute to the toxic mechanism of action of methyl mercury in isolated cerebellar granule neurons.

ISSN:0736-5748    

DOI:10.1016/0736-5748(91)90005-7

出版商:Wiley    

年代:2003

数据来源: WILEY

摘要:

AbstractThe neurotoxin, l‐methyl‐4‐phenyl‐l,2,3,6‐tetrahydropyridine, has been shown to cause pooling of blood in the brain microvasculature and decrease the permeability of the blood‐brain barrier. All areas of the brain examined in this study were affected. This study points out the possibility that reduced nutrient uptake, hypoxia and ensuing free radical damage are involved in the mechanism of toxicity of this neurotoxin.

ISSN:0736-5748    

DOI:10.1016/0736-5748(91)90006-8

出版商:Wiley    

年代:2003

数据来源: WILEY

摘要:

AbstractRetinoic acid is a naturally occurring metabolite of vitamin A that influences the differentiation of a variety of neural cellsin vitro. In the LA‐N‐1 human neuroblastoma line, retinoic acid treatment increases the binding of nerve growth factor (Bmax). The purpose of this study was to examine the effects of retinoic acid on PC12 rat pheochromocytoma, a neural crest‐derived cell line that can be induced to express a sympathetic neuroblast‐like phenotype by nerve growth factor treatment. In contrast to the differentiating effects of nerve growth factor, retinoic acid treatment of PC12 cells had a negligible effect on cellular morphology. However, treatment with retinoic acid enhanced the survival of PC12 cells following oxidative injury generated by H2O2treatment in a manner that is qualitatively similar to that observed after nerve growth factor treatment. Also, there was an increase in125I‐nerve growth factor binding activity in solubilized PC12 membrane preparations derived from retinoic acid‐treated PC12 cells. These data suggest that retinoic acid may play a role in neuronal development and in neuronal injury by stimulating the ability of neurons to cope with oxidative stress and/or by enhancing neuronal responsiveness to trophic factors such as the nerve growth factor.

ISSN:0736-5748    

DOI:10.1016/0736-5748(91)90007-9

出版商:Wiley    

年代:2003

数据来源: WILEY

摘要:

AbstractThe administration of high doses of methamphetamine causes long lasting damage to central dopaminergic and serotonergic neurons through a mechanism known to involve presynaptic, cytoplasmic stores of those transmitters and thought to be dependent upon a free radical reaction. The following studies were designed to determine if differential inhibition of the subtypes of monoamine oxidase would alter the magnitude of the methamphetamine induced neuronal damage. In addition, since monoamine oxidase type B increases with age, the effects of high dose administration of methamphetamine were evaluated in sensescent mice. It was observed that inhibition of monoamine oxidase type A, and to a lesser degree, type B, increased the magnitude of methamphetamine‐induced neuronal damage and that aged mice were more sensitive to the toxic action of methamphetamine. These results are interpreted with respect to the use of monoamine oxidase inhibitors in the treatment of Parkinson's disease.

ISSN:0736-5748    

DOI:10.1016/0736-5748(91)90008-A

出版商:Wiley    

年代:2003

数据来源: WILEY

摘要:

AbstractHead trauma with cerebral contusion causes extravasation of red blood cells, followed by hemolysis and deposition of iron‐containing blood products within the neuropil. Liberation of heme compounds is associated with deposition of hemosiderin, and with gliosis, neuronal loss and occasionally the development of seizures. In this experiment we injected components of red blood cell contents into rat amygdala, and then measured the rate of appearance of products of lipid peroxidation. Injection of microliter volumes of hemin and hemoglobin, with hematoprotoporphyrin and rodent plasma injection and contralateral uninjected tissue as controls, showed that the presence of the iron moiety within the protoporphyrin ring was required to initiate and propagate peroxidation. Free radical reactions initiated by iron or heme deposited within the neuropil may be a fundamental reaction associated with brain injury responses, and possibly with posttraumatic epileptogenesis.

ISSN:0736-5748    

DOI:10.1016/0736-5748(91)90009-B

出版商:Wiley    

年代:2003

数据来源: WILEY

摘要:

AbstractBecause the developing brain is subject to high oxygen tension and lacks a functional blood‐brain barrier, anti‐oxidant protection is important to development in the brain. The levels of superoxide dismutase, copper‐zinc superoxide dismutase. manganese superoxide dismutase. catalase, glutathione and related enzymes, namely, glutathione reductase and glutathione peroxidase were determined in rat brain at various stages of development. The levels of thiobarbituric acid reactive products, indicative of lipid peroxidation, were very low at birth and increased to adult levels by the 16th day after birth. Brain glutathione levels displayed significant variations during the first 2 weeks after birth but not thereafter. Catalase activity in developing brain slowly increased over 45 days. Total superoxide dismutase activity in 1‐day‐old rat brain, 80% of the adult rat brain level, subsequently decreased on day 6. Total superoxide dismutase activity, however, increased again in 10‐day‐old rats and remained constant thereafter. While the developmental pattern of manganese superoxide dismutase was similar to that of the total superoxide dismutase, the copper‐zinc superoxide dismutase levels were low at birth and reached adult levels on the 10th day after birth. There was no variation in glutathione reductase and peroxidase levels except for a decrease on day 16 of glutathione reductase and slow increase in adult levels by day 28. The present findings suggest that the overall levels of antioxidant enzymes in the developing brain are comparable to a large extent to those present in the adult brain. In contrast to the developing brain, hepatic levels of glutathione, total superoxide dismutase, manganese superoxide dismutase are significantly lower at birth and increase during development.

ISSN:0736-5748    

DOI:10.1016/0736-5748(91)90010-J

出版商:Wiley    

年代:2003

数据来源: WILEY