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| 2. |
- Drake, M., et al.
(författare)
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The immunosuppressant FK506 ameliorates ischaemic damage in the rat brain
- 1996
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772. ; 158:2, s. 155-159
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Tidskriftsartikel (refereegranskat)abstract
- The effect of the immunosuppressant FK506 on ischaemic neuronal damage was studied in a rat model of transient cerebral ischemia induced by occlusion of both common carotid arteries in combination with hypotension for 10 min. Neuronal damage was assessed morphologically after 4 days of recovery. Treatment with FK506, given at a dose of 2 mg kg-1 by intraperitoneal injections 30 min prior to ischemia and once daily during recovery, decreased neuronal damage by 52% in the hippocampal CA1 region and by 48% in the temporal cortex. The protection was not due to diminished body temperature or a marked reduction of ischaemia-induced synaptic overflow of glutamate. We propose that FK506 decreases neuronal damage either by inhibiting calcineurin-mediated events or by preserving mitochondrial function.
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| 3. |
- Hardebo, J. E., et al.
(författare)
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Excitatory amino acids and cerebrovascular tone
- 1989
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772. ; 136:3, s. 483-485
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Tidskriftsartikel (refereegranskat)abstract
- Levels of excitatory amino acids in the brain extracellular fluid compartment rise during pathological conditions in the brain such as ischaemia, anoxia and epilepsy. One such amino acid, glutamate, is present in sensory nerve fibres innervating, for example, cerebral vessels. Enhanced levels of circulating glutamate and aspartate are found in migraine sufferers. The present study examined whether excitatory amino acids, in concentrations found in the brain extracellular fluid compartment during pathological conditions, exert a direct effect on cerebrovascular tone. As tested in flow-regulating pial arteries from rat, cat and man, no such constrictive or dilatory effect was obtained.
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| 4. |
- NELLGÅRD, B., et al.
(författare)
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NMDA‐receptor blockers but not NBQX, an AMPA‐receptor antagonist, inhibit spreading depression in the rat brain
- 1992
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Ingår i: Acta Physiologica Scandinavica. - : Wiley. - 0001-6772 .- 1365-201X. ; 146:4, s. 497-503
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Tidskriftsartikel (refereegranskat)abstract
- The effect of different glutamate‐receptor antagonists on the induction of cortical spreading depression of Leao and of cortical anoxic membrane depolarization were investigated in the anaesthetized rat. Spreading depression (SD), elicited by mechanical stimulation of the cortical surface, was inhibited by the non‐competitive N‐methyl‐d‐aspartate (NMDA)‐receptor blocker, (±)‐5‐methyl‐10,11‐dihydro‐SH‐dibenzo(a, d)‐cyclo‐hepten‐5,10‐imine maleate (dizocilpine or MK‐801), (0. 30 μmol kg‐1 (0. 10 mg kg ‐1)), and the competitive NMDA‐receptor antagonists; cis‐4‐phosphonomethyl‐2‐piperidine carboxylate (CGS 19755), (3.36 μmol kg‐1 (0.75 mg kg‐1)), d‐(E)‐2‐amino‐4‐methyl‐5‐phosphono‐3‐pentenoic acid (CGP 40116), (1.20 μmol kg‐1 (0.25 mg kg‐1)) and its carboxylester CGP 43487, (6.30 μmol kg‐1 (1.50 mg kg‐1)). The α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepripriate (AMPA)‐receptor blocker, 2,3‐dihydroxy‐6‐nitro‐7‐sulfamoyl‐benzo(F) quinoxaline (NBQX), administered as an intravenous dose of 29.76 and 89.29 μmol kg‐1 (10 & 30 mg kg‐1), which is sufficient to block seizures and protect against ischaemic brain damage, did not inhibit spreading depression. None of the drugs utilized inhibited the anoxic membrane depolarization. The data demonstrate that NMDA‐receptor activation is essential for the initiation and propagation of spreading depression, while activation of AMPA‐receptors is not obligatory. The observed initiation and propagation of SD, during AMPA‐receptor blockade, suggest that activation of voltage‐operated ion channels may contribute to release the magnesium block of the NMDA‐receptor operated channel and to the initiation of SD.
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| 5. |
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| 6. |
- 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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