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| 2. |
- Hougaard, Kjeld, et al.
(författare)
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Cerebral metabolic and circulatory effects of 1,1,1-trichloroethane, a neurotoxic industrial solvent - 1. Effects on local cerebral glucose consumption and blood flow during acute exposure
- 1984
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Ingår i: Neurochemical Pathology. - 0734-600X. ; 2:1, s. 39-53
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Tidskriftsartikel (refereegranskat)abstract
- The effects of inhaled 1,1,1-trichloroethane (3500, 6000, and 7800 ppm) on behavior, local cerebral blood flow, and local cerebral glucose consumption were studied in awake rats. The effect of the solvent inhalation on the EEG pattern and local cerebral blood flow was also studied in paralyzed animals under N2O analgesia. Exposure of awake animals to 6000 ppm 1,1,1-trichloroethane induced a decrease in motility and exploratory behavior. At 7800 ppm the rats were clearly ataxic. The local cerebral glucose consumption in 23 brain regions was studied by the [14C]deoxyglucose technique. A decrease was observed ranging from 14 to 55% of control values. The inferior colliculus and substantia nigra displayed the largest reductions. In exposed animals the local cerebral blood flow increased in 11 brain structures by 28-45%. In animals under N2O analgesia, 7400 ppm 1,1,1-trichloroethane induced a depression of the EEG activity. In these animals the local cerebral blood flow increased by 12-99%, with a large variability in blood flow between the different structures. It is concluded that exposure of rats to subanesthetic doses of 1,1,1-trichloroethane induces an increase in cerebral blood flow in spite of a concomitant decrease in glucose consumption and depression of cerebral function.
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| 3. |
- Katsura, Ken Ichiro, et al.
(författare)
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Acidosis enhances translocation of protein kinase C but not Ca2+/calmodulin-dependent protein kinase II to cell membranes during complete cerebral ischemia
- 1999
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Ingår i: Brain Research. - 0006-8993. ; 849:1-2, s. 119-127
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Tidskriftsartikel (refereegranskat)abstract
- Systemic hyperglycemia and hypercapnia severely aggravate ischemic brain damage when instituted prior to cerebral ischemia. An aberrant cell signaling following ischemia has been proposed to be involved in ischemic cell death, affecting protein kinase C (PKC) and the calcium calmodulin kinase II (CaMKII). Using a cardiac arrest model of global brain ischemia of 10 min duration, we investigated the effect of hyperglycemia (20 mM) and hypercapnia (pCO2 300 mmHg) on the subcellular redistribution of PKC (α, β, γ) and CaMKII to synaptic membranes and to the microsomes, as well as the effect on PKC activity. We confirmed the marked translocation of PKC and CaMKII to cell membranes induced by ischemia, concomitantly with a decrease in the PKC activity in both the membrane fraction and cytosol. Hyperglycemia and hypercapnia markedly enhanced the translocation of PKC-γ to cell membranes while other PKC isoforms were less affected. There was no effect of acidosis on PKC activity, or on translocation of CaMKII to cell membranes. Our data strongly suggest that the enhanced translocation of PKC to cell membranes induced by hyperglycemia and hypercapnia may contribute to the detrimental effect of tissue acidosis on the outcome following ischemia. Copyright (C) 1999 Elsevier Science B.V.
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| 6. |
- Kurihara, J, et al.
(författare)
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Hyperglycemia and hypercapnia differently affect post-ischemic changes in protein kinases and protein phosphorylation in the rat cingulate cortex
- 2004
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Ingår i: Brain Research. - : Elsevier BV. - 1872-6240 .- 0006-8993. ; 995:2, s. 218-225
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Tidskriftsartikel (refereegranskat)abstract
- Hyperglycemia and hypercapnia aggravate intra-ischemic acidosis and subsequent brain damage. However, hyperglycemia causes more extensive post-ischemic damage than hypercapnia, particularly in the cingulate cortex. We investigated the changes in the subcellular distribution of protein kinase Cgamma(PKCgamma) and the Ca2+/calmodulin-dependent protein kinase II (CaMKII), as well as changes in protein tyrosine phosphorylation during and following 10 min normoglycemic, hyperglycemic (plasma glucose - 20 mM) and hypercapnic (paCO(2) - 300 mm Hg) global cerebral ischemia. During reperfusion period, the translocation to cell membranes of PKCgamma, but not CaMKII, was prolonged by intra-ischemic hyperglycemia, while it was only marginally affected by hypercapnia. The tyrosine-phosphorylation of proteins in the synaptosomal membranes, as well as the extracellular signal-regulated kinase (ERK) in the cytosol, markedly increased during reperfusion following hyperglycemic ischemia, but to a lesser degree following hypercapnic ischemia. Our data suggest that PKCgamma, tyrosine kinase and ERK systems are involved in the process of ischemic damage in the cingulate cortex, where hyperglycemia may affect these kinases through an additional mechanism other than exaggerated acidosis. (C) 2003 Elsevier B.V. All rights reserved.
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| 8. |
- Smith, Maj‐Lis ‐L, et al.
(författare)
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Models for studying long‐term recovery following forebrain ischemia in the rat. 2. A 2‐vessel occlusion model
- 1984
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 69:6, s. 385-401
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Forskningsöversikt (refereegranskat)abstract
- ABSTRACT— A model is described in which transient ischemia is induced in rats anaesthetized with N2O:O2 (70:30) by bilateral carotid artery clamping combined with a lowering of mean arterial blood pressure to 50 mm Hg, the latter being achieved by bleeding, or by bleeding supplemented with administration of trimetaphan or phentolamine. By the use of intubation, muscle paralysis with suxamethonium chloride, and insertion of tail arterial and venous catheters, it was possible to induce reversible ischemia for long‐term recovery studies. Autoradiographic measurements of local CBF showed that the procedure reduced CBF in neocortical areas, hippocampus, and caudoputamen to near‐zero values, flow rates in a number of subcortical areas being variable. Administration of trimethaphane or phentolamine did not affect ischemic and postischemic flow rates, nor did they alter recovery of EEG and sensory‐evoked responses, but trimetaphan blunted the changes in plasma concentrations of adrenaline and noradrenaline. Recovery experiments showed that 10 min of ischemia gave rise to clear signs of permanent brain damage, with a small number of animals developing postischemic seizures that led to the death of the animals in status epilepticus. After 15 min of ischemia, such alterations were more pronounced, and the majority of animals died. It is concluded that the short revival times noted are explained by the fact that the model induces near‐complete ischemia, and that recovery following forebrain ischemia is critically dependent on residual flow rates during the period of ischemia.
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| 9. |
- Uchino, H, et al.
(författare)
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Amelioration by cyclosporin A of brain damage in transient forebrain ischemia in the rat
- 1998
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Ingår i: Brain Research. - 1872-6240. ; 812:1-2, s. 216-226
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Tidskriftsartikel (refereegranskat)abstract
- The immunosuppressant drug cyclosporin A (CsA) is considered to be inherently protective in conditions of ischemia, e.g. in hepatic and cardiac tissue. However, investigations of effects of CsA on neuronal tissue have been contradictory, probably because the blood-brain barrier (BBB) is virtually impermeable to CsA. In the present study, we exploited the finding that the insertion of a syringe needle into brain parenchyma obviously disrupts the BBB and allows influx of CsA, and explored whether CsA, given as intraperitoneal injections daily for 1 week before and 1 week after forebrain ischemia of 7 or 10 min duration, ameliorates the damage incurred to the hippocampal CA 1 sector. In other experiments, the needle insertion and the first i.p. injection of CsA were made 30 min after the start of recirculation, with continued daily administration of CsA during the postinsult week. In animals which were injected with CsA in daily doses of 10 mg kg-1, but in which no needle was inserted, the drug failed to ameliorate CA1 damage, whether the ischemia had a duration of 7 or 10 min. Likewise, needle insertion had no effect on CA1 damage if CsA was not administered. In contrast, when CsA was given to animals with a needle insertion, CA1 damage was dramatically ameliorated, whether treatment was initiated 1 week before ischemia, or 30 min after the start of recirculation. The effect of CsA seemed larger than that of any other drug proposed to have an anti-ischemic effect in forebrain/global ischemia. Injection of tritiated CsA in one animal with BBB disruption lead to detectable radioactivity throughout the ventricular system, suggesting a generalised increase of the entry of CsA across the BBB. The results demonstrate that immunosuppressants of the type represented by CsA markedly ameliorate delayed neuronal damage after transient forebrain ischemia, provided that they can pass the BBB. It is discussed whether the effect of the drug is one involving calcineurin, a protein phosphatase, or if CsA counteracts a permeability transition of the inner mitochondrial membrane, assumed to occur in response to adverse conditions, e.g. gradual accumulation of Ca2+ in the mitochondria in the postischemic period.
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