| 1. |
- Boris-Möller, Fredrik, et al.
(författare)
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The effect of hypothermia on the expression of neurotrophin mRNA in the hippocampus following transient cerebral ischemia in the rat
- 1998
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Ingår i: Molecular Brain Research. - 0169-328X. ; 63:1, s. 163-173
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Tidskriftsartikel (refereegranskat)abstract
- The expression of the mRNAs of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3) and the neurotrophin receptor, TrkB, was studied in the rat hippocampus by in situ hybridization following normothermic (37°C) and protective hypothermic (33°C) transient cerebral ischemia of 15 min duration. In the resistant dentate gyms, normothermic ischemia transiently induced NGF mRNA at around 8 h of recovery, while the NT3 mRNA levels were depressed over at least a 24-h recovery period. The levels of BDNF and TrkB were transiently and markedly elevated with a maximal expression at 24 h of recovery. Intraischemic hypothermia reduced the induction of NGF mRNA, while the increase of BDNF mRNA expression occurred earlier during recovery, and the post-ischemic NT3 mRNA depression was not affected. Also, the expression of TrkB mRNA was enhanced, and occurred concomitantly with the elevation of BDNF mRNA. In contrast, there were no changes in neurotrophin and TrkB mRNA in the CA3 and CA1 regions. The expression of BDNF mRNA at 24 h after normothermic ischemia, was attenuated by intraischemic hypothermia. We conclude that, the expressions of NGF, BDNF, NT3 or TrkB mRNA in ischemia-sensitive hippocampal subregions are not increased by protective hypothermia. In contrast, hypothermia induces neurotrophin mRNA alterations in the ischemia-resistant dentate gyms that may convey protection to sensitive regions.
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| 2. |
- Allers, Mats, et al.
(författare)
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A New Method of Selective, Rapid Cooling of the Brain: An Experimental Study.
- 2006
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Ingår i: Cardiovascular and Interventional Radiology. - : Springer Science and Business Media LLC. - 1432-086X .- 0174-1551. ; 29:2, s. 260-263
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To determine whether retrograde perfusion of cooled blood into one internal jugular vein (IJV) in the pig can selectively reduce the brain temperature without affecting the core body temperature (CBT). Methods: In 7 domestic pigs, the left IJV was catheterized on one side and a catheter placed with the tip immediately below the rete mirabile. Thermistors were placed in both brain hemispheres and the brain temperature continuously registered. Thermistors placed in the rectum registered the CBT. From a catheter in the right femoral vein blood was aspirated with the aid of a roller pump, passed through a cooling device, and infused into the catheter in the left IJV at an initial rate of 200 ml/min. Results: Immediately after the start of the infusion of cooled blood (13.8 degrees C) into the IJV, the right brain temperature started to drop from its initial 37.9 degrees C and reached 32 degrees C within 5 min. By increasing the temperature of the perfusate a further drop in the brain temperature was avoided and the brain temperature could be kept around 32 degrees C during the experiment. In 4 of the animals a heating blanket was sufficient to compensate for the slight drop in CBT during the cooling period. Conclusions: We conclude that brain temperature can be reduced in the pig by retrograde perfusion of the internal jugular vein with cooled blood and that the core body temperature can be maintained with the aid of a heating blanket.
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| 3. |
- Boris-Möller, Fredrik, et al.
(författare)
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Changes in the extracellular levels of glutamate and aspartate during ischemia and hypoglycemia. Effects of hypothermia
- 1998
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Ingår i: Experimental Brain Research. - : Springer Science and Business Media LLC. - 0014-4819 .- 1432-1106. ; 121:3, s. 277-284
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Tidskriftsartikel (refereegranskat)abstract
- Hypothermia (33°C) dramatically diminishes ischemic but not hypoglycemic brain damage. The beneficial effects of hypothermia in ischemia have been partly attributed to a reduction in the ischemia-induced increase in synaptic levels of glutamate or aspartate. With the microdialysis technique, we studied the effects of hypothermia (33°C) on the brain extracellular levels of glutamate and aspartate during hypoglycemia, ischemia, and their combination. In isoelectric hypoglycemia, striatal levels of glutamate and aspartate frequently show large transients of transmitter release occurring during both normothermia and hypothermia, whereas in the cortex levels of glutamate and aspartate are slightly lower during hypothermia compared with normothermia. In both regions studied, complete ischemia induced by i.v. KCl results in a progressive increase in glutamate and aspartate levels over time. In normoglycemic animals, hypothermia markedly attenuates the increase in glutamate and aspartate levels in the striatum but not in the cortex. Also in hypoglycemic animals, complete ischemia causes a progressive increase in the glutamate and aspartate levels. However, hypothermia affects only striatal glutamate levels. Since hypothermia protects both cortex and striatum against ischemic brain injury and not against hypoglycemic injury, presumably the protective effect of hypothermia is due to factors other than prevention of glutamate or aspartate overflow.
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| 4. |
- Boris-Möller, Fredrik, et al.
(författare)
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The effect of 4β-phorbol-12,13-dibutyrate and staurosporine on the extracellular glutamate levels during ischemia in the rat striatum
- 1998
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Ingår i: Molecular and Chemical Neuropathology. - 1044-7393. ; 35:1-3, s. 133-147
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Tidskriftsartikel (refereegranskat)abstract
- Hypothermia diminishes the ischemia-induced protein kinase C (PKC) translocation and inhibition, and also reduces transmitter release during ischemia. To study the role of PKC in the mechanism of glutamate release during ischemia, we measured extracellular glutamate levels in the striatum with the microdialysis technique, in the presence and absence in the dialysate of the PKC activator 4β-phorbol-12,13-dibutyrate (PDBu) and the protein kinase inhibitor staurosporine. We confirm that hypothermia attenuates the elevation of extracellular levels of glutamate in the striatum during ischemia. In the presence of PDBu, the glutamate levels in the dialysate increased from 0.3 μmol/L to an end ischemic level of 4.8 μmol/L during hypothermic ischemia (33°C). These levels were significantly higher than in hypothermic ischemia (33°C) without added PDBu. Staurosporine significantly mitigated the glutamate levels during normothermic ischemia. Our data suggest that PKC is involved in the temperature-dependent elevations of extracellular glutamate levels in the striatum during ischemia, and we propose that compounds preventing PKC activation may mimic the hypothermic protective action against ischemic brain damage.
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| 5. |
- Coimbra, Cicero, et al.
(författare)
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Diminished neuronal damage in the rat brain by late treatment with the antipyretic drug dipyrone or cooling following cerebral ischemia
- 1996
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 92:5, s. 447-453
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Tidskriftsartikel (refereegranskat)abstract
- It has been shown that changes in body core temperature several hours after a transient ischemic insult affect neuronal survival. We report that body core temperature in normal rats fluctuates over a 24-h period, while in rats subjected to 10 min transient ischemia induced by occlusion of the common carotid arteries in combination with hypotension, body temperature persistently increases to above 38.5°C from 21 to 63 h following recirculation. The antipyretic drug dipyrone administered from 12 to 72 h recovery depresses body temperature to normothermic values and markedly diminishes neuronal damage in the neocortex and hippocampus when evaluated at 7 days of survival. Cooling the animals down to normothermic levels provided similar protection to that obtained with dipyrone treatment. These results suggest that hyperthermia occurring late during reperfusion aggravates delayed neuronal damage and can be effectively prevented by antipyretic drugs. The data imply that: (1) temperature-dependent processes occurring late during recovery are involved in delayed neuronal death, (2) inflammation may be an important factor in delayed neuronal death, (3) prostanoids and interleukins may contribute to this process (4) postischemic prolonged (days) temperature control is required for proper evaluation of drug therapy in brain ischemia models, and (5) fever in patients suffering brain ischemia should be impeded.
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| 6. |
- Coimbra, Cicero, et al.
(författare)
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Long-lasting neuroprotective effect of postischemic hypothermia and treatment with an anti-inflammatory/antipyretic drug : Evidence for chronic encephalopathic processes following ischemia
- 1996
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Ingår i: Stroke. - 0039-2499. ; 27:9, s. 1578-1585
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: It has been recognized that postischemic pharmacological interventions may delay the evolution of neuronal damage rather than provide long-lasting neuroprotection. Also, fever complicates recovery after stroke in humans. Here we report the effects of late postischemic treatment with hypothermia and an antipyretic/anti-inflammatory drug, dipyrone, on cell damage at 1 week and 2 months of survival. Methods: Rats were subjected to 10 minutes of forebrain ischemia hypothermia (33°C) was induced at 2 hours of recovery and maintained for 7 hours. Dipyrone (100 mg · kg-1 IP) was given every 3 hours from 14 to 72 hours of recovery. Temperature was measured every 6 hours for 60 days. Neuronal damage was assessed at 7 days and 2 months of recovery. Results: From 17 to 72 hours of recovery, a period of hyperthermia was observed, which dipyrone abolished but postischemic hypothermia treatment did not. Dipyrone treatment diminished neuronal damage by 43% at 7 days, and at 2 months of survival, a minor (16%) protection was seen. Postischemic hypothermia treatment alone delayed neuronal damaged. In contrast, combined treatment of hypothermia followed by dipyrone markedly diminished neuronal damage by more than 50% at both 7 days and 2 months of recovery. Conclusions: Neuronal degeneration may be ongoing for months after a transient ischemic insult, and prolonged protective measures need to be instituted for long-lasting neuroprotective effects. Hyperthermia during recovery worsens ischemic damage, and processes associated with inflammatory may contribute to the development of neuronal damage. An early and extended period of postischemic hypothermia provides a powerful and long-lasting protection if followed by treatment with anti- inflammatory/antipyretic drugs.
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| 7. |
- Säveland, Hans, et al.
(författare)
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Intracerebral microdialysis of glutamate and aspartate in two vascular territories after aneurysmal subarachnoid hemorrhage
- 1996
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Ingår i: Neurosurgery. - : Ovid Technologies (Wolters Kluwer Health). - 0148-396X .- 1524-4040. ; 38:1, s. 12-20
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Tidskriftsartikel (refereegranskat)abstract
- CEREBRAL ISCHEMIA ASSOCIATED with subarachnoid hemorrhage may have severe consequences for neuronal functioning. The excitatory amino acid neurotransmitters glutamate and aspartate have been shown to he of particular importance for ischemia and ischemic neuronal damage. For seven patients who underwent early surgery for ruptured intracranial aneurysms, intracerebral microdialysis of glutamate and aspartate was performed to monitor local metabolic changes in the medial temporal (all seven patients) and subfrontal cortex (Patients 4 through 7). Samples were collected every 30 or 60 minutes, using an autosampler. The results show that extracellular glutamate and aspartate concentrations can rise to very high levels after surgery for subarachnoid hemorrhage and aneurysm. These increased levels of excitatory amino acids correlated well with the clinical course and neurological symptoms of the patients. Simultaneous sampling from two vascular territories (middle cerebral artery and anterior cerebral artery) also showed that a rise in extracellular glutamate and aspartate in one territory is not necessarily parallel with a rise in the other. The application of the microdialysis technique with an on-line assay system might be of value in the future for continuous monitoring of ischemic events to optimize treatment with, for example, blockers of glutamatergic neurotransmission.
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| 8. |
- Wieloch, Tadeusz, et al.
(författare)
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Hög tid att pröva hypotermi i behandlingen av slaganfall
- 2001
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Ingår i: Läkartidningen. - 0023-7205. ; 98:18, s. 2172-2175
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Tidskriftsartikel (refereegranskat)abstract
- There is a revived clinical interest in hypothermia as a neuroprotective intervention in brain ischemia. This originates from the experimental finding that hypothermia of only 3 degrees C-4 degrees C below normal body temperature completely abolishes neuronal damage from an ischemic insult that is lethal in normothermia. The idea that hypothermia protects cells from ischemic damage mainly by lowering metabolic rate is challenged. We propose that detrimental protein-lipid interactions in brain cells, that are activated during and following brain ischemia and that mediate adverse cellular signaling and lead to cell death, are blunted or prevented by mild hypothermia.
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