| 11. |
- Westerberg, E., et al.
(författare)
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Dynamic changes of excitatory amino acid receptors in the rat hippocampus following transient cerebral ischemia
- 1989
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Ingår i: The Journal of Neuroscience. - 0270-6474. ; 9:3, s. 798-805
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Tidskriftsartikel (refereegranskat)abstract
- The changes in excitatory amino acid receptor ligand binding induced by transient cerebral ischemia were studied in the rat hippocampal subfields. Ten minutes of ischemia was induced by common carotid artery occlusion combined with hypotension, and the animals were allowed variable periods of recovery ranging from 1 day to 4 weeks. The binding of 3H-AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) to quisqualate receptors, 3H-kainic acid (KA) to kainate receptors, and 3H-glutamate to N-methyl-D-aspartate (NMDA) receptors as determined by quantitative autoradiography. One week following ischemia the CA1 region of the hippocampus displayed a severe (90%) dendrosomatic lesion with preservation of presynaptic terminals. This was associated with a 60% decrease in AMPA binding and a 25% decrease in glutamate binding to NMDA receptors. At 4 weeks postischemia, both AMPA and NMDA sites were greatly reduced. Although the dentate gyrus granule cells are resistant to an ischemic insult of this magnitude, this region showed marked changes in receptor binding. One week following ischemia, the AMPA and NMDA binding decreased by approximately 40 and 20%, respectively. Following 2 weeks of recovery, the NMDA binding was not significantly different from control level, while the AMPA binding remained depressed up to 4 weeks postischemia. The high density of KA binding sites in the inner molecular layer of the dentate gyrus was unaffected by the ischemic insult, despite an extensive degeneration of cells in the hilus of dentate gyrus which projects glutamatergic afferents to this area.
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| 12. |
- Wieloch, T., et al.
(författare)
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Changes in the Activity of Protein Kinase C and the Differential Subcellular Redistribution of Its Isozymes in the Rat Striatum During and Following Transient Forebrain Ischemia
- 1991
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Ingår i: Journal of Neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 56:4, s. 1227-1235
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Tidskriftsartikel (refereegranskat)abstract
- Abstract: The changes in the levels of protein kinase C [PKC(α, βII, γ)] were studied in cytosolic and particulate fractions of striatal homogenates from rats subjected to 15 min of cerebral ischemia induced by bilateral occlusion of the common carotid arteries and following 1 h, 6 h, and 48 h of reperfusion. During ischemia the levels of PKC(βII) and ‐(γ) increased in the particulate fraction to 390% and 590% of control levels, respectively, concomitant with a decrease in the cytosolic fraction to 36% and 20% of control, respectively, suggesting that PKC is redistributed from the cytosol to cell membranes. During reperfusion the PKC(βII) levels in the particulate fraction remained elevated at 1 h postischemia and decreased to below control levels after 48 h reperfusion, whereas PKC(γ) rapidly decreased to subnormal levels. In the cytosol PKC(βII) and ‐(γ) decreased to 25% and 15% of control levels at 48 h, respectively. The distribution of PKC(α) did not change significantly during ischemia and early reperfusion. The PKC activity in the particulate fraction measured in vitro by histone IIIS phosphorylation in the presence of calcium, 4β‐phorbol 13‐myristate 12‐acetate, and phosphatidylserine (PS) significantly decreased by 52% during ischemia, and remained depressed over the 48‐h reperfusion period. In the cytosolic fraction PKC activity was unchanged at the end of ischemia, and decreased by 47% after 6 h of reperfusion. The appearance of a stable cytosolic 50‐kDa PKC‐immunoreactive peptide or an increase in the calcium‐and PS‐independent histone IIIS phosphorylation was not observed. Consequently, during ischemia PKC, preferentially PKC(γ) and PKC(βII), is translocated from the cytosol and inserted into cell membranes, concomitant with a decrease in PKC activity. In the reperfusion phase the depression of PKC activity persists and the enzyme is degraded. The observed translocation and downregulation of PKC during ischemia and reperfusion may be of significance for the development of ischemic neuronal damage.
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| 13. |
- Auer, R. N., et al.
(författare)
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The distribution of hypoglycemic brain damage
- 1984
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Ingår i: Acta Neuropathologica. - 0001-6322. ; 64:3, s. 177-191
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Tidskriftsartikel (refereegranskat)abstract
- Rats were exposed to insulin-induced hypoglycemia resulting in periods of cerebral isoelectricity ranging from 10 to 60 min. After recovery with glucose, they were allowed to wake up and survive for 1 week. Control rats were recovered at the stage of EEG slowing. After sub-serial sectioning, the number and distribution of dying neurons was assessed in each brain region. Acid fuchsin was found to stain moribund neurons a brilliant red. Brains from control rats showed no dying neurons. From 10 to 60 min of cerebral isoelectricity, the number of dying neurons per brain correlated positively with the number of minutes of cerebral isoelectricity up to the maximum examined period of 60 min. Neuronal necrosis was found in the major brain regions vulnerable to several different insults. However, within each region the damage was not distributed as observed in ischemia. A superficial to deep gradient in the density of neuronal necrosis was seen in the cerebral cortex. More severe damage revealed a gradient in relation to the subjacent white matter as well. The caudatoputamen was involved more heavily near the white matter, and in more severely affected animals near the angle of the lateral ventricle. The hippocampus showed dense neuronal necrosis at the crest of the dentate gyrus and a gradient of increasing selective neuronal necrosis medially in CA1. The CA3 zone, while relatively resistant, showed neuronal necrosis in relation to the lateral ventricle in animals with hydrocephalus. Sharp demarcations between normal and damaged neuropil were found in the hippocampus. The periventricular amygdaloid nuclei showed damage closest to the lateral ventricles. The cerebellum was affected first near the foramina of Luschka, with damage occurring over the hemispheres in more severely affected animals. Purkinje cells were affected first, but basket cells were damaged as well. Rare necrotic neurons were seen in brain stem nuclei. The spinal cord showed necrosis of neurons in all areas of the gray matter. Infarction was not seen in this study. The possibility is discussed that a neurotoxic substance borne in the tissue fluid and cerebrospinal fluid (CSF) contributes to the pathogenesis of neuronal necrosis in hypoglycemic brain damage.
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| 14. |
- Auer, R., et al.
(författare)
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The dentate gyrus in hypoglycemia : Pathology implicating excititoxin-mediated neuronal necrosis
- 1985
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Ingår i: Acta Neuropathologica. - 0001-6322. ; 67:3-4, s. 279-288
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Tidskriftsartikel (refereegranskat)abstract
- A detailed light- and electron-microscopic study of the damage to the rat dentate gyrus in hypoglycemia was undertaken, in view of the previously advanced hypothesis that hypoglycemic nerve cell injury is mediated by a released neurotoxin. The distribution of neuronal necrosis showed a relationship to the subarachnoid cisterns. Electron microscopy of the dentate granule cells and their apical dendrites revealed dendrosomal, axon-sparing neuronal pathology. Dentate granule cells were affected first in the dendrites in the outer layer of the stratum moleculare, sparing axons of passage and terminal boutons. Subsequently, the neuronal perikarya were affected, and Wallerian degeneration of axons followed. Cell membrane abnormalities preceded the appearance of mitochondrial flocculent densities and degradation of the cytoskeleton, and are suggested to be early lethal changes. The observed early dendrotoxic changes, and the dendrosomal, axon-sparing nature of the lesion implicate an excitotoxin-mediated neuronal necrosis in hypoglycemia.
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| 15. |
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| 16. |
- Bentzer, Peter, et al.
(författare)
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Infusion of prostacyclin following experimental brain injury in the rat reduces cortical lesion volume
- 2001
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 1557-9042 .- 0897-7151. ; 18:3, s. 275-285
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Tidskriftsartikel (refereegranskat)abstract
- Endothelial-derived prostacyclin is an important regulator of microvascular function, and its main actions are inhibition of platelet/leukocyte aggregation and adhesion, and vasodilation. Disturbances in endothelial integrity following traumatic brain injury (TBI) may result in insufficient prostacyclin production and participate in the pathophysiological sequelae of brain injury. The objective of this study was to evaluate the potential therapeutic effects of a low-dose prostacyclin infusion on cortical lesion volume, CA3 neuron survival and functional outcome following TBI in the rat. Anesthetized animals (sodium pentobarbital, 60 mg/kg, i.p.) were subjected to a lateral fluid percussion brain injury (2.5 atm) or sham injury. Following TBI, animals were randomized to receive a constant infusion of either prostacyclin (1 ng/kg x min(-1) i.v.) or vehicle over 48 h. All sham animals received vehicle (n = 6). Evaluation of neuromotor function, lesion volume, and CA3 neuronal loss was performed blindly. By 7 days postinjury, cortical lesion volume was significantly reduced by 43% in the prostacyclin-treated group as compared to the vehicle treated group (p < 0.01; n = 12 prostacyclin, n = 12 vehicle). No differences were observed in neuromotor function (48 h and 7 days following TBI), or in hippocampal cell loss (7 days following TBI) between the prostacyclin- and vehicle-treated groups. We conclude that prostacyclin in a low dose reduces loss of neocortical neurons following TBI and may be a potential clinical therapeutic agent to reduce neuronal cell death associated with brain trauma.
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| 17. |
- Bergstedt, K., et al.
(författare)
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Changes in insulin-like growth factor 1 receptor density after transient cerebral ischemia in the rat : Lack of protection against ischemic brain damage following injection of insulin-like growth factor 1
- 1993
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 13:5, s. 895-898
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Tidskriftsartikel (refereegranskat)abstract
- Binding of 125I-insulin-like growth factor-1 (125I-IGF-1) to rat brain slices was studied after 15 min of two-vessel occlusion ischemia and 1 h to 4 days of recirculation. Ligand binding in the hippocampus increased at 6 h post ischemia in the CA1 and CA3 regions and the dentate gyrus, suggesting that the IGF-1 receptors were up-regulated, while no change was seen in neocortex and striatum. Intracerebroventricular injections of IGF-1 (2 μg) prior to and after transient cerebral ischemia did not reduce neuronal damage. The increased up-regulation on IGF-1 receptors and the absence of neuroprotection by IGF-1 suggest that the intracellular signal transduction chain activated by the IGF-1 receptor may be interrupted.
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| 18. |
- Blomqvist, P., et al.
(författare)
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Delayed postischemic hypoperfusion : Evidence against involvement of the noradrenergic locus ceruleus system
- 1984
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 4:3, s. 425-429
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Tidskriftsartikel (refereegranskat)abstract
- This study explores the possibility that the delayed hypoperfusion observed after an ischemic insult might be due to vasoconstriction induced by the release of noradrenaline from nerves originating in the locus ceruleus. Bilateral 6-hydroxydopamine lesions of the ascending bundles from the locus ceruleus were carried out in the caudal mesencephalon of rats. Local CBF was measured with an autoradiographic technique 60 min following the start of recirculation after incomplete forebrain ischemia. No significant differences in CBF between nonoperated, sham-operated, and noradrenaline-depleted animals were observed in any structure of the forebrain. It is concluded that the noradrenergic locus ceruleus system does not contribute to the development of delayed postischemic hypoperfusion.
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| 19. |
- 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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| 20. |
- Cardell, M., et al.
(författare)
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Changes in pyruvate dehydrogenase complex activity during and following severe insulin-induced hypoglycemia
- 1991
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 11:1, s. 122-128
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Tidskriftsartikel (refereegranskat)abstract
- The effect of severe insulin-induced hypoglycemia on the activity of the pyruvate dehydrogenase enzyme complex (PDHC) was investigated in homogenates of frozen rat cerebral cortex during burst suppression EEG, after 10, 30, and 60 min of isoelectric EEG, and after 30 and 180 min and 24 h of recovery following 30 min of hypoglycemic coma. Changes in PDHC activity were correlated to levels of labile organic phosphates and glycolytic metabolites. In cortex from control animals, the rate of [1-14C]pyruvate decarboxylation was 7.1 ± 1.3 U/mg of protein, or 35% of the total PDHC activity. The activity was unchanged during burst suppression EEG whereas the active fraction increased to 81-87% during hypoglycemic coma. Thirty minutes after glucose-induced recovery, the PDHC activity had decreased by 33% compared to control levels, and remained significantly depressed after 3 h of recovery. This decrease in activity was not due to a decrease in the total PDHC activity. At 24 h of recovery, PDHC activity had returned to control levels. We conclude that the activation of PDHC during hypoglycemic coma is probably the result of an increased PDH phosphatase activity following depolarization and calcium influx, and allosteric inhibition of PDH kinase due to increased ADP/ATP ratio. The depression of PDHC activity following hypoglycemic coma is probably due to an increased phosphorylation of the enzyme, as a consequence of an imbalance between PDH phosphatase and kinase activities. Since some reduction of the ATP/ADP ratio persisted and since the lactate pyruvate ratio had normalized by 3 h of recovery, the depression of PDHC most likely reflects a decrease in PDH phosphatase activity, probably due to a decrease in intramitochondrial Ca2+.
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