Influence of transient ischemia on lipid-soluble antioxidants, free fatty acids and energy metabolites in rat brain

Yoshida, Shigeaki; Abe, Kouichi; Busto, Raul; Watson, Brant D.; Kogure, Kyuya; Ginsberg, Myron D.

doi:10.1016/0006-8993(82)90813-7

Cited by 214 publications

(73 citation statements)

References 49 publications

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“…Such evidence includes decreases in ascorbate (reduced form) and ot-tocopherol and an increase in conjugated dienes. 112 - 13 Thus, although no radical species have yet been directly detected, it seems to be widely accepted that a certain species of free radicals may exist and may play a role in ischemic and/or postischemic brain damage. 1 ' 5 There are two pathways generating peroxidative reactions in damaged brain as well as in any tissue.…”

mentioning

confidence: 99%

Strong attenuation of ischemic and postischemic brain edema in rats by a novel free radical scavenger.

Abe

Yuki

Kogure

1988

Stroke

360

189

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Regional changes in the amount of free fatty acids, polyphosphoinositides, and water content in the cerebral cortex were examined using a middle cerebral artery occlusion model of rats. The amount of various free fatty acids increased as polyphosphoinositides decreased during 3 and 6 hours of ischemia in the occluded middle cerebral artery territory. After 3 hours of reperfusion following 3 hours of ischemia, free fatty acids partially recovered while polyphosphoinositides did not. Water content increased significantly after 3 and 6 hours of ischemia, and a further increase was found after 3 hours of reperfusion following 3 hours of ischemia. The change of polyenoic fatty acids in this occluded middle cerebral artery territory was much smaller than that in the case of decapitation ischemia, although the amounts of polyphosphoinositides and monoenoic and saturated fatty acids showed almost identical changes in both cases, probably because polyenoic fatty acids may be washed out and/or peroxidatively consumed in the middle cerebral artery occlusion model due to its residual blood flow. Changes in the area surrounding the occluded middle cerebral artery territory were similar to the above results, although less dramatic However, there was no change in free fatty acids, polyphosphoinositides, and water content in the contralateral cortex. A novel free radical scavenger (MCI-186), which prevents both nonenzymatic peroxidation and lipoxygenase activity in vitro, markedly attenuated the ischemic and postischemk brain swelling. These results suggest that free radical mechanisms may be involved in ischemk and postischemic brain edema. A peroxidative mechanism has been implicated as one of the detrimental factors in ischemic and postischemic brain cell damage. 1 "4 Since Demopoulos 5 indicated the possibility of free radical damage in ischemic brain, various approaches have been tried in an effort to detect some species of oxygen radicals in the ischemic or postischemic brain. However, all attempts have failed to detect oxygen radicals in vivo and in situ because of their short half-lives and/or because of methodologic difficulties involved in trapping and extracting such radicals.*"" Due to the above reasons, only indirect evidence has been obtained indicating the generation of free radicals during and after ischemia. Such evidence includes decreases in ascorbate (reduced form) and ot-tocopherol and an increase in conjugated dienes. 112 -13 Thus, although no radical species have yet been directly detected, it seems to be widely accepted that a certain species of free radicals may exist and may play a role in ischemic and/or postischemic brain damage. 1 ' 5 There are two pathways generating peroxidative reactions in damaged brain as well as in any tissue. One is an auto-oxidation (nonenzymatic peroxidation) and the other is enzyme-processing peroxidation. Nonenzymatic peroxidations have been artificially generated in vitro using brain slices, and they were shown to induce brain swelling. 14 " 17 Cell damage induced by t...

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mentioning

confidence: 99%

Strong attenuation of ischemic and postischemic brain edema in rats by a novel free radical scavenger.

Abe

Yuki

Kogure

1988

Stroke

360

189

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“…Under normal conditions, the concentrations of FFA, acyl2Gro, and icosanoids in brain tissue are very low (10,13). However, certain pathological conditions, such as hypoglycemia, status epilepticus, hypoxia, ischemia, and cold injury, cause the levels of these compounds to rise dramatically (14)(15)(16)(17)(18)(19)(20)(21).…”

mentioning

confidence: 99%

Membrane lipid changes in laminectomized and traumatized cat spinal cord.

Demediuk¹,

Saunders²,

Anderson³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

157

105

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Free fatty acid (FFA), diacyiglycerol (acyl2-Gro), icosanoid, phospholipid, and cholesterol levels were measured in samples of cat spinal cord (L2) that were frozen in situ (i) with vertebrae intact, (ii) at various times after laminectomy, and (iu) at various times after laminectomy with compression trauma to the spinal cord. Tissue samples either were grossly dissected into gray and white portions prior to FFA and acyl2Gro analysis or were used whole for the other lipid types. Gray matter total FFA and acyl2Gro values were abnormally high in samples frozen with vertebrae intact and in those frozen 10 min after laminectomy. This indicates that the surgical procedures resulted in some perturbation of spinal cord lipid metabolism. If the experimental animals were allowed to recover for 90 min after laminectomy, the gray matter FFA and acyl2Gro levels were greatly reduced. Compression of the spinal cord with a 170-g weight for 1, 3, or 5mm (following 90 min of recovery after laminectomy) caused significant elevations of total FFA, acyl2Gro, icosanoids, and phosphatidic acid and significant decreases in ethalamine plasmalogens and cholesterol. Among the total FFA, arachidonic acid was found to have the largest relative increase. Comparisons of gray and white matter demonstrate that, in general, changes in white matter FFA and acyl2Gro were similar to those seen in gray matter. However, the increases in white matter levels of FFA and acyl2Gro were delayed, occurring after the elevations in gray matter. For some FFA (e.g., arachidonate), the rise in white matter occurred as gray matter levels were decreasing. This suggests that the initial alteration in spinal cord lipid metabolism after trauma was in gray matter but, with time, spread radially into white matter.

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“…19 In brief, the animals were prepared as follows: The vertebral arteries were electrocoagulated under halothane anesthesia. One day later, anesthesia was induced with diethyl ether.…”

Section: Methodsmentioning

confidence: 99%

“…ethylene tubing-ligatures as described previously. 19 Since preliminary studies had shown that forebrain levels of high-energy phosphate compounds during ischemia varied considerably among animals and tended to correlate with the degree of EEG suppression during ischemia and mean arterial blood pressure levels during recirculation, the following criteria were utilized in the present study to ensure uniform severity of ischemia: 1) total abolition of EEG activity within 1 min from the onset of carotid occlusion; 2) isoelectric EEG throughout the occlusion; and 3) maintenance of mean arterial blood pressure above 90 mm Hg during the recirculation period. To ensure uniform, severe ischemia, the blood pressure was reduced to 100-110 mm Hg by controlled arterial hemorrhage into a heparinized plastic syringe, beginning 10 min prior to the onset of carotid occlusion (total amount 4-5 ml).…”

Section: Methodsmentioning

confidence: 99%

Verapamil: failure of metabolic amelioration following global forebrain ischemia in the rat.

Berger

Busto

Ginsberg³

1984

Stroke

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1029SUMMARY The potential efficacy of the calcium channel blocker verapamil in modifying ischemic brain injury was evaluated in anesthetized rats subjected to 60 or 90 min of diffuse forebrain ischemia produced by bilateral occlusion of the carotid and vertebral arteries. Treated animals received verapamil, 2 mg/kg intravenously, prior to ischemia. Four hours of postischemic recirculation was permitted by reversing the carotid occlusions. Intermittent high-voltage slow-wave activity was noted on electroencephalograms shortly after verapamil infusion, prior to ischemia. The ischemic insult induced an isoelectric EEG, which tended to persist during recirculation in both treated and untreated animals. Similarly, verapamil pretreatment failed to influence brain water content or cerebral energy metabolites (phosphocreatine, ATP, ADP, AMP) or cerebral energy charge when assayed after four hours of recirculation. Thus, verapamil failed to confer a protective effect on brain electrical activity, water content, or energy metabolites following ischemia in this model. Stroke Vol 15, No 6, 1984 CONSIDERABLE RECENT ATTENTION has been devoted to the role of perturbed calcium ion homeostasis in contributing to hypoxic-ischemic cellular injury.1 ' 2 Normally, intracellular calcium ion activity is regulated at a level several orders of magnitude less than that of the extracellular space.3 During cerebral ischemia, extracellular calcium ion activity has been shown to decline at cerebral blood flows below 6-9 ml/ 100 g/min, concomitant with membrane depolarization as signalled by rising extracellular potassium ion activity, 4 suggesting that the opening of voltage-dependent calcium ion channels within the plasma membrane has permitted the intracellular influx of this ion. 1In addition, the energy failure of ischemia results in a release of calcium from its normal ATP-dependent sites of sequestration in the endoplasmic reticulum. 5 Finally, ischemia impairs the ability of mitochondria to accumulate calcium. 6 The resulting increase in free cytoplasmic calcium activity disrupts a variety of cellular functions 6 and, in particular, may be responsible in part for the breakdown of membrane phospholipids and massive release of free fatty acids due to stimulation of phospholipases.1 ' 7i 8 The latter events, in turn, have been implicated in contributing to irreversible cellular injury.A deleterious effect of the intracellular influx of calcium is strongly suggested by recent studies in extracerebral tissue. Schanne et al 9 reported that hepatocytes cultured in a calcium-depleted medium were able to withstand exposure to a variety of otherwise noxious membrane-active toxins. Farber and colleagues demonstrated that survival of heart and liver cells following prolonged ischemia is markedly improved by blocking calcium influx with chlorpromazine.7 Calcium channel blockers, including verapamil, have been demonstrated to preserve myocardial function in the face of ischemic injury.1(M2 In isolated rat hearts subjected to global ischemia, ver...

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Influence of transient ischemia on lipid-soluble antioxidants, free fatty acids and energy metabolites in rat brain

Cited by 214 publications

References 49 publications

Strong attenuation of ischemic and postischemic brain edema in rats by a novel free radical scavenger.

Strong attenuation of ischemic and postischemic brain edema in rats by a novel free radical scavenger.

Membrane lipid changes in laminectomized and traumatized cat spinal cord.

Verapamil: failure of metabolic amelioration following global forebrain ischemia in the rat.

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