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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leukotrienes are powerful metabolites of arachidonic acid which are known to increase the permeability of peripheral blood vessels. These substances are found in brain tissue in association with cerebral ischemia, and in brain tumors. Therefore, it has been proposed that leukotrienes have a mediator function in brain edema. This hypothesis was subjected to further experimental analysis in this study, in which the authors investigated whether: 1) superfusion of the exposed brain surface with leukotrienes increases the permeability of extraparenchymal blood vessels in vivo; 2) intraparenchymal infusion of leukotrienes induces brain edema; and 3) pharmacological inhibition of leukotriene formation by BW755C, an inhibitor of leukotriene synthesis, reduces formation of brain edema from a standardized traumatic insult. The pial vessels of the parietal cortex of cats were examined by fluorescence microscopy during cerebral superfusion with the leukotrienes C4 (LTC4), D4 (LTD4), or E4 (LTE4) by using an open cranial window preparation. Intravenous Na(+)-fluorescein served as an in vivo blood-brain barrier (BBB) indicator. Superfusion of the pia with leukotrienes (up to 2 microM) did not open the barrier to fluorescein, but was associated with a significant constriction (up to 25%) of arterial and venous vessels. In experiments with slow infusion of leukotriene B4 (LTB4) or LTC4 into the white matter of feline brain, the tissue water content was subsequently determined in serial brain slices using the specific gravity method. Tissue water profiles obtained after a 15-microM infusion of either LTB4 or LTC4 were virtually identical with those of control animals infused with mock cerebrospinal fluid. Thus, neither LTB4 nor LTC4 led to an augmentation of infusion-induced brain edema. In a final series, a cold lesion of the left parietal cortex was induced in rabbits. Twenty-four hours later, swelling of the exposed hemisphere was quantified by gravimetrical comparison of its weight with that of the contralateral nontraumatized hemisphere. Eight animals received BW755C intravenously prior to and after trauma to inhibit formation of leukotrienes. Seven rabbits were infused with an equivalent volume of saline as a control study. The resulting hemispheric swelling was 7.7% +/- 0.6% (mean +/- standard error of the mean) 24 hours later in animals receiving BW755C and 7.8% +/- 1.2% in the control group, indicating that inhibition of leukotrienes was ineffective in preventing formation of vasogenic brain edema. The findings demonstrate that leukotrienes administered to the brain in concentrations occurring under pathological conditions do not open the BBB nor do they induce brain edema.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Evidence against leukotrienes as mediators of brain edema. 173 Sep 68

The effects of nilvadipine, a Ca2+ entry blocker, on focal cerebral ischemia were investigated in rats having unilateral middle cerebral artery occlusion. All rats had 24 h ischemia, and were divided into three groups (ten rats per group). Groups 1 and 2 received 1.0 and 3.2 mg/kg nilvadipine s.c. respectively, just after the occlusion. Control rats received an equal volume of the vehicle. Control animals had a % infarct volume of 28.2 +/- 11.4%, and a left/right hemispheric volume ratio of 112 +/- 12%. Group-1 and -2 rats had % infarct volumes of 25.5 +/- 11.6% and 13.9 +/- 9.2% (p less than 0.01) respectively, and left/right hemispheric volume ratios of 111 +/- 9% and 103 +/- 7% (p less than 0.05), respectively. Thus, the drug reduced the infarct size and the brain edema in a dose-dependent manner. The significant decrease in the infarct volume was observed in the periphery of the frontoparietal cortex. This study supports the hypothesis that nilvadipine may be a potential therapeutic agent for cerebral ischemia. Neuropathological findings suggest the possible therapeutic effects of the drug in the ischemic penumbra.
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PMID:Effects of a Ca2+ entry blocker (nilvadipine) on acute focal cerebral ischemia in rats. 202 49

Recent advances in high-resolution MR imaging and multinuclear spectroscopy have stimulated studies of the functional relationships between tissue hypoperfusion, cellular energy depletion, and brain edema associated with cerebral ischemia. The very slow (microns/sec) random translational motion of water protons in various brain tissues and intracranial fluid compartments can now be assessed with MR diffusion imaging. More slowly diffusing protons in ischemic tissues can be differentiated from normal parenchyma, CSF, and flowing blood, enabling the detection and localization of ischemic regions within minutes of the onset of stroke. Perfusion imaging "snapshots," obtained in as little as 25 msec with echoplanar MR methods, permit the evaluation of tissue washin/washout kinetics of contrast agents in the microvasculature, and thus the quantification of brain perfusion on a regional basis. Also, delineation of major intra- and extracranial arterial and venous structures with MR angiography, acquired with two- or three-dimensional Fourier transformation techniques, has enabled accurate noninvasive assessments of vascular occlusive disease. Finally, improvements in MR spectroscopic techniques have facilitated investigations of metabolic regulation and bioenergetics in experimental animal models of cerebral ischemia, as well as in stroke patients. Combined MR imaging and spectroscopy will likely play an important role in differentiating reversibly from irreversibly ischemic brain tissues and in the investigation of various neuroprotective pharmaceuticals.
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PMID:Recent advances in MR imaging/spectroscopy of cerebral ischemia. 202 55

Arachidonic acid is liberated from damaged cell membranes during ischemia and is the source of vasoactive prostanoids. In this study, specific drugs that influence AA metabolism were investigated for their effects on brain edema and energy metabolites during ischemia. The agents tested were: methylprednisolone (phospholipase A2 inhibition), indomethacin (cyclooxygenase inhibitor), trapidil (TXA2 synthetase inhibitor), and OP-41483 (prostacyclin derivative). Cerebral ischemia was produced using bilateral common carotid artery occlusion in spontaneously hypertensive rats. Brain water content and concentrations of ATP, pyruvate, and lactate were determined 3 hr after occlusion. Compared with its vehicle, methylprednisolone significantly reduced water content and lactate concentration and maintained high levels of ATP. Indomethacin had no effect on brain water content nor metabolite levels. Trapidil decreased water content and lactate levels and increased levels of ATP and pyruvate. OP-41483 had no effect on water content and lactate, but maintained ATP and pyruvate at high levels. These results indicate that some of the AA metabolites may play an important role in the development of brain edema and in the impairment of energy metabolism.
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PMID:Role of arachidonic acid metabolism on ischemic brain edema and metabolism. 211 11

Perfluorochemicals were developed as a blood substitute and were reported to have an advantage in oxygen transport compared with blood. The present study was undertaken to investigate the therapeutic effects of a perfluorochemical, FDA, on brain edema and metabolites in acute cerebral ischemia. Cerebral ischemia was induced in SHR by BLCO followed by recirculation. The FDA administration resulted in (a) the significant inhibition of brain edema as shown by brain water content in the treated group, and (b) significant amelioration of metabolic impairments as shown by lesser degree of ATP and pyruvate decrease and lactate accumulation. The TpO2 was compared between FDA-infused and nontreated group during ischemia. The FDA-infused group had significantly higher TpO2 than nontreated group. These results indicate that the improvement of brain edema and metabolite levels were due to alleviation of ischemic hypoxia by FDA under the same ischemic insult.
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PMID:Effects of fluosol-DA on brain edema, energy metabolites, and tissue oxygen content in acute cerebral ischemia. 211 12

Leukotrienes accumulate in brain tissue after cerebral ischemia and in brain tumors. Thus, their release might contribute to the blood-brain barrier damage observed under these conditions and, hence, brain edema. The effect of these substances on the permeability of pial vessels and whether inhibition of LT synthesis reduces cold injury brain edema were studied. The pial vasculature of cats was studied by fluorescence microscopy. The cortex was superfused with LTC4, LTD4, or LTE4 via a cranial window. Na(+)-fluorescein was intravenously administered as blood-brain barrier indicator. LT concentrations up to 2 microM did not induce any leakage of the blood-brain barrier indicator into the parenchyma. However, all LTs tested constricted pial arteries and veins. Brain edema formation was studied in rabbits with cold injury. BW755C, an inhibitor of cyclooxygenase and lipoxygenase preventing formation of LTs, was given before and after trauma. Control animals received saline only. BW755C was ineffective in attenuating cold injury edema. Hemispheric swelling in control animals was 7.8 +/- 1.1%, and 7.7 +/- 0.4% in animals with treatment. LTs, even when administered to the brain in concentrations exceeding levels occurring under pathological conditions, did not induce barrier damage, nor did inhibition of LT synthesis attenuate formation of vasogenic edema. The results provide further evidence against LTs as mediator compounds of this process.
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PMID:Role of leukotrienes as mediator compounds in brain edema. 211 15

Endogenous opioids have been shown to produce beneficial effects in experimental stroke. To evaluate both neurophysiological and biochemical parameters, we induced massive cerebral ischemia in 11 rabbits according to the method standardized in our laboratory, using microspheres injected through the internal carotid artery. Binding studies were performed in the 11 embolized, in nine control, and in five sham-operated rabbits using the appropriate concentration of [3H]dynorphin A (1-8). Neurophysiological parameters were evaluated under baseline conditions and 1 hour after embolization, surgical preparation, or sham operation in 17 rabbits. Comparison of visual readings of the electroencephalograms and analyses of the quantified electroencephalograms under baseline conditions and after embolization indicated a marked and statistically significant (p less than 0.01) increase in bilateral delta activity; histologic examination confirmed bilateral brain edema. Binding studies on kappa-opioid receptors indicate that 1 hour after embolization there were significantly more (28%) kappa-opioid receptors (Bmax) in six embolized rabbits than in five sham-operated animals. No significant changes were observed in the affinity parameters, particularly in the dissociation constant (Kd). Our results indicate a role for endogenous dynorphin peptides in the pathogenesis of stroke.
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PMID:Kappa-opioid receptor changes and neurophysiological alterations during cerebral ischemia in rabbits. 216 75

Oxygen-derived free radicals have been postulated to be involved in brain edema and cell death secondary to ischemia and traumatic injury. Using a model of vasogenic brain edema produced by a permanent occlusion of the left MCA in rats, we have studied the role of superoxide radicals in pathogenesis of ischemic edema. The levels of NBF in ischemic brain were increased by 222%, 420%, and 614%, respectively, at 1, 4, and 24 hr after the MCAO. Topical application of superoxide dismutase to the injured cortex through a modified cranial window significantly reduced the NBF levels, indicating the involvement of superoxide radicals in ischemic brain. Liposome-entrapped SOD, when IV injected 5 min after the MCAO, significantly reduced the degree of edema at 24 hr. Our data indicate that superoxide radicals play an important role in the pathogenesis of vasogenic edema in cerebral ischemia.
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PMID:Pathogenesis of vasogenic edema in focal cerebral ischemia. Role of superoxide radicals. 216 62

Brain edema is a frequent complication of cerebral ischemia; however, its mechanism of formation is not well understood. Sodium is known to accumulate in brain during the early stages of partial ischemia. Therefore, the present studies were undertaken to determine the relation among BBB sodium transport, integrity of the BBB, and development of brain edema during the first 24 hr after the onset of cerebral ischemia. Partial cerebral ischemia was produced in gerbils by ligation of the left common carotid artery under ether anesthesia. After recovery from the anesthetic, animals were scored for the presence of symptoms, and those with scores greater than 10 of 25 (n = 87) were chosen for this study. Measurements of tissue water, sodium, and potassium contents, and brain uptake of 22Na and 3H-mannitol were made in each group at 1.5, 3, 6, 12, and 24 hr after carotid ligation. Accumulation of sodium and water in the ischemic compared with the nonischemic cerebral cortex was progressive. This edema formation was not of the vasogenic type because the permeability of the BBB to mannitol was unchanged. Blood-to-brain sodium transport was reduced by 30% to 40% at all time points in the ischemic cortex. Nevertheless, the remaining sodium transport activity appeared to play a role in the development of brain edema because Na accumulated in the tissue at a rate that was approximately the same as the rate of 22Na uptake from blood.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Blood-to-brain sodium transport in ischemic brain edema. 216 71

The effect of nimodipine pretreatment on CBF and brain edema was studied in conscious rats subjected to 2.5 h of focal cortical ischemia. An infusion of nimodipine (2 micrograms/kg/min i.v.) or its vehicle, polyethylene glycol 400, was begun 2 h before the ischemic interval and was continued throughout the survival period. Under brief halothane anesthesia, the animals' right middle cerebral and common carotid arteries were permanently occluded, and 2.5 h later, they underwent a quantitative CBF study ([14C]iodoantipyrine autoradiography followed by Quantimet 970 image analysis). Nimodipine treatment improved blood flow to the middle cerebral artery territory without evidence of a "vascular steal" and reduced the volume of the ischemic core (cortex with CBF of less than 25 ml/100 g/min) and accompanying edema by approximately 50% when compared with controls (p = 0.006 and 0.0004, respectively). Mild hypotension induced by nimodipine did not aggravate the ischemic insult. The ischemic core volumes, however, were 50-75% smaller than the 24-h infarct volumes generated in a similar paradigm that demonstrated 20-30% infarct reduction with continuous nimodipine treatment. These results suggest that nimodipine pretreatment attenuates the severity of early focal cerebral ischemia, but that with persistent ischemia, cortex surrounding the ischemic core undergoes progressive infarction and the early benefit of nimodipine treatment is only partly preserved.
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PMID:Nimodipine pretreatment improves cerebral blood flow and reduces brain edema in conscious rats subjected to focal cerebral ischemia. 221 83


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