| 1. |
- 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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| 2. |
- 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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| 3. |
- Gustafson, I., et al.
(författare)
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Extracellular brain cortical levels of noradrenaline in ischemia : - Effects of desipramine and postischemic administration of idazoxan
- 1991
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Ingår i: Experimental Brain Research. - 0014-4819. ; 86:3, s. 555-561
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Tidskriftsartikel (refereegranskat)abstract
- Using microdialysis, extracellular noradrenaline (NA) levels in the rat cerebral cortex were studied under isoflurane/N2O anaesthesia before, during and for 6 hours following 10 min of forebrain ischemia in a 2-vessel occlusion model. A microdialysis probe was introduced into the parietal cortex and dorsal hippocampus in anaesthetized rats and continuously perfused with Krebs-Ringerbicarbonate buffer with or without the NA uptake inhibitor desipramine (DMI, 5 μM). Twenty min fractions were collected and the extracellular NA levels were measured in the dialysates using HPLC with electrochemical detection. The basal NA concentration in the dialysate was 10.5±1.8 (mean±SEM) pg/20 min fraction and increased to 39.3±4.8 pg/20 min fraction after local administration of DMI. During ischemia, NA increased to 38 times the basal level without DMI, and 6 times with DMI included during two hours' perfusion prior to ischemia. After recirculation NA levels returned to, or even transiently decreased below, preischemic values. With DMI present in the dialysis buffer, administration of idazoxan immediately following ischemia delayed the return to preischemic NA levels in the recirculation phase. In the absence of DMI, no effect of idazoxan on postischemic levels of NA was found. Local administration of DMI increases basal extracellular NA levels and reduces the ischemia-induced NA release. The latter effect may be a due to inhibition of the NA uptake system working in a reversed mode, or as a result of decreased synthesis of NA due to activation of presynaptic α2-receptors by the increased synaptic NA levels. Postischemic treatment with the α2-adrenoceptor antagonist idazoxan in combination with DMI prolongs the period of elevated extracellular NA levels, which may be of importance for the protective properties of idazoxan against ischemic cell injury.
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| 4. |
- Westerberg, E., et al.
(författare)
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Extracellular levels of quinolinic acid are moderately increased in rat neostriatum following severe insulin-induced hypoglycaemia
- 1990
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Ingår i: Acta Physiologica Scandinavica. - : Wiley. - 0001-6772 .- 1365-201X. ; 138:3, s. 417-422
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Tidskriftsartikel (refereegranskat)abstract
- Extracellular concentrations of the brain metabolite quinolinic acid, an endogenous excitotoxin, were monitored by microdialysis in rat neostriatum and hippocampus/cortex during and following a 30-min period of insulin-induced hypoglycaemia. During hypoglycaemia-induced isoelectricity, extracellular levels of quinolinic acid in the striatum (basal value, 1.1 ± 0.3 pmol per 30-μl fraction) were elevated 1.7 times as compared to the control period. Thirty to ninety minutes following hypoglycaemia a significant increase in extracellular quinolinic acid to 2.2 times basal level was noted. After 2 h recovery, the beginning of neuronal necrosis was observed in the dorsolateral striatum. Implantation of the dialysis probe did not influence the extent of neuronal damage. No changes in extracellular quinolinic acid levels were observed in the hippocampus/cortex. The data indicate the following a severe hypoglycaemic insult vulnerable striatal cells are exposed to hyperphysiological extracellular quinolinic acid concentrations over an extended period of time. Considering the pronounced susceptibility of rat striatal neurons to the toxin, the small but prolonged elevation in the extracellular levels of quinolinic acid could be of significance for the development of delayed neuronal death in hypoglycaemia.
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| 5. |
- Westerberg, E., et al.
(författare)
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Regional differences in arachidonic acid release in rat hippocampal CA1 and CA3 regions during cerebral ischemia
- 1987
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 7:2, s. 189-192
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Tidskriftsartikel (refereegranskat)abstract
- Changes in the levels of arachidonic acid during ischemia in selectively vulnerable areas of the hippocampus were studied in the rat brain. Since neurons in the CA1 region are more vulnerable to ischemia than neurons in the adjacent CA3 region, the release of arachidonic acid in these two regions was measured during decapitation ischemia of 4- to 12-min duration. The concentration of free arachidonic acid increased with the duration of ischemia in both regions. However, the level was significantly higher in CA1 than in CA3 after 8 and 12 min of ischemia. This difference in arachidonic acid accumulation may reflect differences between the regions in agonist-dependent phospholipid breakdown as well as calcium-dependent phospholipase activity. The importance for the development of neuronal necrosis is discussed.
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| 6. |
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| 7. |
- Wieloch, T., et al.
(författare)
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Lesions of the glutamatergic cortico-striatal projections in the rat ameliorate hypoglycemic brain damage in the striatum
- 1985
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Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940. ; 58:1, s. 25-30
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Tidskriftsartikel (refereegranskat)abstract
- Unilateral ablations of the motor cortex were performed on rats. One to two weeks following the ablation they were subjected to 30 min of reversible insulin-induced hypoglycemic coma. The levels of glutamate, aspartate, γ-aminobutyric acid (GABA), taurine, adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and phosphocreatine (PCr) were determined in frozen tissue sections from the superior half of the caudate nucleus. The lesions induced a specific reduction in the levels of glutamate by approx. 10% in the dorsal caudate nucleus ipsilateral to the lesion, while no significant differences in the levels of aspartate, GABA, taurine, ATP, ADP, AMP or PCr were noted. Neuronal necrosis in the caudate nucleus in animals subjected to 30 min of insulin-induced hypoglycemic coma and one week recovery was assessed by light microscopy. Contralateral to the lesion, extensive neuronal necrosis, mainly affecting small and medium-sized neurons, was observed in the dorsal and lateral caudate nucleus. In the caudate ipsilateral to the lesion a complete amelioration of necrosis was noted in areas subjacent to the lesion. The data suggest that hypoglycemic brain damage is induced by excitotoxins such as glutamate or related compounds.
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| 8. |
- Wieloch, T., et al.
(författare)
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Mechanisms of glutamate neurotoxicity in cerebral ischemia
- 1989
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Ingår i: Neurotransmission and cerebrovascular function vol. 2 : proceedings of the International Symposium 'Neurotransmission and Cerebrovascular Function'. ICS870 - proceedings of the International Symposium 'Neurotransmission and Cerebrovascular Function'. ICS870. - 0444811427 ; , s. 393-409
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Konferensbidrag (refereegranskat)
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