| 1. |
- Blomqvist, P., et al.
(författare)
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Ischemic brain damage in rats following cardiac arrest using a long-term recovery model
- 1985
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 5:3, s. 420-431
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Tidskriftsartikel (refereegranskat)abstract
- A model is described in which transient complete cerebral ischemia is induced in rats by intracardiac injection of potassium chloride. The animals were intubated and mechanically ventilated with a nitrous oxide/oxygen (70:30) mixture. Cardiac arrest was achieved following a brief period of ventricular fibrillation. After 5-6 min, the circulation was restored by cardiopulmonary resuscitation and partial exchange transfusion. Local CBF (LCBF) during ischemia and cardiac resuscitation was studied by injection of [14C]iodoantipyrine into the right auricle at various periods during cardiac arrest, and was subsequently analyzed by autoradiography. No radioactive tracer could be visualized in any brain structure, demonstrating the absence of CBF during the cardiac standstill. LCBF was also studied at 5 min and 6.5 h after cardiac resuscitation. Five minutes of recirculation showed an increase in blood flow in all brain structures studied, ranging between 130 and 400% of control values. After 6.5 h of recirculation, the CBF was decreased in 13 of 24 brain structures by 20-50%, concomitantly with the depressed rate of glucose utilization found in 15 brain structures. The neocortical, hippocampal, and striatal concentrations of labile phosphates, lactate, pyruvate, phosphocreatine, glucose, and glucogen were measured 5 min after cardiac arrest. Extensive energy failure and elevation of lactate levels were observed and were similar to earlier reported values. One week following recovery from the ischemic insult, the animals were perfusion-fixed with formaldehyde. The brains were embedded in paraffin, subserially sectioned, and stained with cresyl violet/acid fuchsin. Histopathological changes were assessed by light microscopy as the number of acidophilic or pyknotic neurons. Morphological changes were observed in the hilus of the dentate gyrus, the hippocampal CA1 and subicular regions, the dorsal and lateral septum, the olfactory tubercle, the primary olfactory cortex, the entorhinal cortex, the amygdaloid nuclei, and the reticular nucleus of the thalamus. The distribution of the morphological changes suggests a transsynaptic mechanism, causing neuronal necrosis primarily in the limbic brain areas.
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| 2. |
- Cardell, M., et al.
(författare)
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Pyruvate dehydrogenase activity in the rat cerebral cortex following cerebral ischemia
- 1989
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 9:3, s. 350-357
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Tidskriftsartikel (refereegranskat)abstract
- The effect of cerebral ischemia on the activity of pyruvate dehydrogenase (PDH) enzyme complex (PDHC) was investigated in homogenates of frozen rat cerebral cortex following 15 min of bilateral common carotid occlusion ischemia and following 15 min, 60 min, and 6 h of recirculation after 15 min of ischemia. In frozen cortical tissue from the same animals, the levels of labile phosphate compounds, glucose, glycogen, lactate, and pyruvate were determined. In cortex from control animals, the rate of [1-14C]pyruvate decarboxylation was 9.6 ± 0.5 nmol CO2/(min-mg protein) or 40% of the total PDHC activity. This fraction increased to 89% at the end of 15 min of ischemia. At 15 min of recirculation following 15 min of ischemia, the PDHC activity decreased to 50% of control levels and was depressed for up to 6 h post ischemia. This decrease in activity was not due to a decrease in total PDHC activity. Apart from a reduction in ATP levels, the acute changes in the levels of energy metabolites were essentially normalized at 6 h of recovery. Dichloroacetate (DCA), an inhibitor of PDH kinase, given to rats at 250 mg/kg i.p four times over 2 h, significantly decreased blood glucose levels from 7.4 ± 0.6 to 5.1 ± 0.3 mmol/L and fully activated PDHC. In animals in which the plasma glucose level was maintained at control levels of 8.3 ± 0.5 μmol/g by intravenous infusion of glucose, the active portion of PDHC increased to 95 ± 4%. In contrast, the depressed PDHC activity at 15 min following ischemia was not affected by the DCA treatment. In both DCA + glucose-treated control and recovery groups, the pyruvate levels decreased by 50%. No significant difference in the lactate levels was seen. We conclude that the depressed postischemic PDHC activity is not due to loss of enzyme protein nor to an increased PDH kinase activity, but is probably due to a decreased activity of PDH phosphatase. This could in turn be secondary to a change in the cellular levels of PDH phosphatase regulators, most probably a decreased intramitochondrial concentration of calcium. The postischemic decrease in PDH activity may be related to the postischemic metabolic depression.
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| 3. |
- Chang, J Y, et al.
(författare)
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Serotonin potentiates noradrenaline-induced vasoconstriction through 5-HT1-type receptors in guinea pig basilar artery
- 1989
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - 1559-7016. ; 9:5, s. 713-716
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Tidskriftsartikel (refereegranskat)abstract
- Based on the previous finding that 5-hydroxytryptamine (5-HT) co-exists with norepinephrine (NE) in cerebrovascular sympathetic nerve fibers and can be released during electrical nerve stimulation, the postjunctional interaction between the two amines was studied in isolated basilar artery of guinea pig. A low concentration of 5-HT, which in itself has little or no constrictive effect, potentiated the weak contraction of NE by almost 300%. The amplification was antagonized by methiothepin, but not by ketanserin, and it could be mimicked by methysergide. The marked potentiation is thus probably associated with the 5-HT1-like receptors, which earlier have been found to mediate the direct vasoconstrictive action of 5-HT in this vessel preparation.
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| 4. |
- Deshpande, J. K., et al.
(författare)
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Calcium accumulation and neuronal damage in the rat hippocampus following cerebral ischemia
- 1987
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 7:1, s. 89-95
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Tidskriftsartikel (refereegranskat)abstract
- The present study was undertaken to correlate calcium accumulation with the development of neuronal necrosis following transient ischemia. After 10 min of forebrain ischemia in the rat—a period that leads to reproducible damage of CA1 pyramidal cells—determination of calcium concentration and evaluation of morphological signs of cell body necrosis in the dorsal hippocampus were performed at various recirculation times. Tissue calcium concentration was not different from control at the end of ischemic period and did not change after 3, 6, 12, or 24 h of recirculation. However, after 48 h, calcium content increased significantly, with a further increase being seen after 72 h. At early recovery periods, only scattered necrotic neurons were observed. after 48 h, only 2 of 12 hemispheres showed more than 25 necrotic cells per section. More conspicuous neuronal death was observed after 72 h. The results thus demonstrate that net accumulation of calcium in regio superior of the hippocampus precedes marked necrosis of CA1 pyramidal cells. The results suggest that one primary event in the delayed death of these cells is membrane dysfunction with increased calcium cycling.
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| 5. |
- Grøgaard, B, et al.
(författare)
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Delayed hypoperfusion after incomplete forebrain ischemia in the rat. The role of polymorphonuclear leukocytes.
- 1989
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 9:4, s. 500-5
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Tidskriftsartikel (refereegranskat)abstract
- The role of polymorphonuclear leukocytes (PMNLs) in postischemic delayed hypoperfusion in the rat brain was investigated. Cerebral ischemia was accomplished by reversible bilateral occlusion of the common carotid arteries for 15 min combined with bleeding to an MABP of 50 mm Hg. The animals of one group were depleted of their circulating. PMNLs by intraperitoneal injections of an antineutrophil serum (ANS) prior to the experiment. All animals included in this group had fewer than 0.2 x 10(9) circulating PMNLs/L at the start of the experiments. In another group ANS was injected intravenously for 5 min starting 2 min after the ischemic insult. After 4 min of recirculation, the number of circulating PMNLs in this group was below 10% of the normal. Control animals were injected with the same amount of normal sheep serum or were not treated at all. Sixty minutes after termination of ischemia, the local blood flow in previously ischemic cerebral structures was 40-50% of the normal as measured with the [14C]iodoantipyrine technique. In animals treated with ANS prior to the ischemic insult, the postischemic blood flow in the frontal, sensorimotor, and parietal cortex as well as caudoputamen and thalamus was significantly higher than that in non-ANS-treated animals. Treatment with ANS immediately after the ischemic period caused no improvement of the local CBF. It is concluded that PMNLs are involved in the cerebral postischemic flow derangements seen in this model. Their effects seem to be exerted during ischemia or immediately upon reinstitution of blood flow.
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| 6. |
- Gustafson, I., et al.
(författare)
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Postischemic administration of idazoxan, an α-2 adrenergic receptor antagonist, decreases neuronal damage in the rat brain
- 1989
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 9:2, s. 171-174
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Tidskriftsartikel (refereegranskat)abstract
- The effect of an α-2 receptor antagonist, idazoxan, on ischemic neuronal damage in the hippocampus and neocortex was studied in rats following 10 min of forebrain ischemia. Idazoxan was given 0.1 mg/kg i.v. immediately after recirculation, followed by 48 h of continuous infusion at a rate of 10 μg/kg/min. A histopathological examination of the CA1 region of the dorsal hippocampus and neocortex from each hemisphere was made on paraffin-embedded sections following 7 days of survival. In ischemic animals receiving an infusion of saline, 71% of the neurons in the hippocampal CA1 region were degenerated. In contrast, in the idazoxan-treated animals only 31% of the neurons were irreversibly damaged (p < 0.01). We conclude that postischemic administration of the α-2 antagonist idazoxan protects neurons against damage following cerebral ischemia. Rapid postischemic administration of α-2 adrenergic receptor antagonists could be an effective treatment after stroke and cardiac arrest.
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| 7. |
- Koide, T., et al.
(författare)
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Chronic dexamethasone pretreatment aggravates ischemic neuronal necrosis
- 1986
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 6:4, s. 395-404
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Tidskriftsartikel (refereegranskat)abstract
- This study addresses the question of whether the cyclooxygenase inhibitors indomethacin and diclofenac and the glucocorticosteroid dexamethasone ameliorate neuronal necrosis following cerebral ischemia. In addition, since these drugs inhibit the production of prostaglandins and depress phospholipase A2 activity, respectively, the importance of free fatty acids (FFAs) on the development of ischemic neuronal damage was assessed. Neuronal damage was determined in the rat brain at 1 week following 10 min of forebrain ischemia. The cyclooxygenase inhibitors, whether given before or after ischemia, failed to alter the brain damage incurred. Animals given dexamethasone were divided into three groups and the drug was administered at a constant dosage of 2 mg/kg: (a) 2 days, 1 day, and 3 h intraperitoneally before (chronic pretreatment), (b) 3 h intraperitoneally before (acute pretreatment), and (c) 5 min intravenously and 6 h and 1 day intraperitoneally after (chronic posttreatment) induction of ischemia. Acute pretreatment did not affect the histopathological outcome. Chronic posttreatment of animals with dexamethasone ameliorated the damage inflicted on the caudate nucleus, but had no effect on other brain areas investigated. Unexpectedly, the chronic pretreatment aggravated the brain damage and caused seizures following ischemia. Histopathological data showed massive neuronal damage in these brains. The accumulation of FFA levels during ischemia was markedly suppressed, and the decrease in the energy charge was curtailed by chronic pretreatment with dexamethasone. However, brain glucose levels in control animals and lactic acid concentrations following 10 min of ischemia were significantly higher both in the cerebral cortex and in the hippocampus of dexamethasone-treated animals. These results suggest that aggravation of neuronal necrosis by chronic dexamethasone pretreatment could be ascribed to lactic acidosis due to hyperglycemia in combination with an action of dexamethasone on glucocorticoid receptors in the brain.
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| 8. |
- Koide, T., et al.
(författare)
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Circulating catecholamines modulate ischemic brain damage
- 1986
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 6:5, s. 559-565
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Tidskriftsartikel (refereegranskat)abstract
- In search of factors influencing the outcome of an ischemic insult, we induced 10 min of forebrain ischemia in rats and assessed neuronal necrosis by quantitative histopathology after 1 week of recovery. Procedures for inducing ischemia included bilateral carotid artery clamping and reduction of blood pressure to 40–50 mm Hg by bleeding. To facilitate rapid lowering of blood pressure, a ganglionic blocker, trimethaphan (TMP), was administered at the onset of ischemia. Omission of the ganglionic blocker proved to markedly ameliorate neuronal damage. Similarly favorable effects were obtained when a mixture of adrenaline and noradrenaline (1 μg kg−1 min−1 each) was infused during the early recirculation period in animals previously given TMP. Infusion of noradrenaline alone also ameliorated the damage, though the efficacy was somewhat less. The results suggest that catecholamines, released as a response to stress, ameliorate ischemic brain damage.
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| 9. |
- Rodriguez, G, et al.
(författare)
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Sex differences in regional cerebral blood flow.
- 1988
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 8:6, s. 783-789
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Tidskriftsartikel (refereegranskat)abstract
- Regional cerebral blood flow was measured by the 133-xenon inhalation method during resting in 38 healthy men and 38 healthy women matched pairwise for age in the range 18-72 years. The results showed 11% higher global flow level in the women in all ages. A similar and significant regression of flow by age was seen for both sexes. The regional flow distribution also showed some sex-related differences. Frontal regions showed an asymmetry in the men with higher values on the right side. The female flows were more symmetric. As a hypothesis, it is suggested that the higher flow level in women may be a systemic phenomenon. In fact, other authors have found a higher cardiac index in females. The sex differences in regional flow pattern might be due to differences in the functional organization of the cortex and/or to differences in the mental processes of the "resting" state.
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| 10. |
- Siesjo, B. K., et al.
(författare)
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Influence of acidosis on lipid peroxidation in brain tissues in vitro
- 1985
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 5:2, s. 253-258
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Tidskriftsartikel (refereegranskat)abstract
- To study the influence of acidosis on free radical formation and lipid peroxidation in brain tissues, homogenates fortified with ferrous ions and, in some experiments, with ascorbic acid were equilibrated with 5–15% O2 at pH values of 7.0, 6.5, 6.0, and 5.0, with subsequent measurements of thiobarbituric acid-reactive (TBAR) material, as well as of water- and lipid-soluble antioxidants (glutathione, ascorbate, and α-tocopherol) and phospholipid-bound fatty acids (FAs). Moderate to marked acidosis (pH 6.5–6.0) was found to grossly exaggerate the formation of TBAR material and the decrease in α-tocopherol content and to enhance degradation of phospholipid-bound, polyenoic FAs. These effects were reversed at pH 5.0, suggesting a pH optimum at pH 6.0–6.5. It is concluded that acidosis of a degree encountered in ischemic brain tissues has the potential of triggering increased free radical formation. This effect may involve increased formation of the protonated form of superoxide radicals, which is strongly prooxidant and lipid soluble, and/or the decompartmentalization of iron bound to cellular macromolecules like ferritin.
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