| 1. |
- Tomasevic, Gregor, et al.
(författare)
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The tumor suppressor p53 and its response gene p21(WAF1/Cip1) are not markers of neuronal death following transient global cerebral ischemia
- 1999
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Ingår i: Neuroscience. - 0306-4522. ; 90:3, s. 781-792
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Tidskriftsartikel (refereegranskat)abstract
- The tumor suppressor protein p53 is implicated in cell cycle arrest and DNA repair as well as in apoptosis. In the CNS, p53 has been associated with neuronal cell death following various insults, including cerebral ischemia. We investigated the expression of p53 messenger RNA and protein, and the messenger RNA expression of the p53-responsive gene p21(WAF1/Cip1), in specific hippocampal regions following 15 min of normothermic and neuroprotective hypothermic (33°C) global forebrain ischemia in the rat. Both p53 and p21(WAF1/Cip1) messenger RNAs were transiently induced in ischemia resistant regions following normo- and hypothermic ischemia. In the ischemia sensitive CA1 region, p53 and p21(WAF1/Cip1) messenger RNAs were up- regulated throughout reperfusion following the normothermic insult. The p53 protein levels increased following the insult, most markedly in ischemia- resistant CA3 neurons after normothermic ischemia, and in the CA1 neurons following hypothermic ischemia. Concomitantly, the protein was translocated to nuclei. These findings indicate that p53 and p21(WAF1/Cip1) are not markers of neuronal death following global cerebral ischemia. Their rapid and transient induction correlates with cell survival, and suggests a possible role in DNA repair.
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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. |
- Anderson, Kevin J., et al.
(författare)
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Ischemia-induced upregulation of excitatory amino acid transport sites
- 1993
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Ingår i: Brain Research. - 0006-8993. ; 622:1-2, s. 93-98
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Tidskriftsartikel (refereegranskat)abstract
- The response of excitatory amino acid transporter binding sites in the rat brain to 10 min of cerebral ischemia induced by bilateral common carotid occlusion combined with hypotension was examined. We observed a transient increase in the density of transporter binding sites that was first noticeable at 5 min post-recovery and persisted for 48 h. The increase in binding sites was found throughout the brain, but was most prevalent in hippocampus and other cortical regions. We conclude that delayed neuronal death following transient cerebral ischemia may not be due to a decrease in the number of excitatory amino acid transport sites.
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| 4. |
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| 5. |
- 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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| 6. |
- Bergstedt, Kerstin, et al.
(författare)
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Initiation of protein synthesis and heat-shock protein-72 expression in the rat brain following severe insulin-induced hypoglycemia
- 1993
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Ingår i: Acta Neuropathologica. - 0001-6322. ; 86:2, s. 145-153
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Tidskriftsartikel (refereegranskat)abstract
- Following stress such as heat shock or transient cerebral ischemia, global brain protein synthesis initiation is depressed through modulation of eucaryotic initiation factor (eIF) activities, and modification of ribosomal subunits. Concomitantly, expression of a certain class of mRNA, heat-shock protein (HSP) mRNA, is induced. Here we report that the activity of eucaryotic initiation factor-2 (eIF-2), a protein that participates in the regulation of a rate-limiting initiation step of protein synthesis, transiently decreases following insulin-induced severe hypoglycemia in the rat brain neocortex. Expression of HSP 72, a 72-kDa HSP, in surviving neurons was seen at 1-7 days of recovery following 30 min of hypoglycemic coma, but not at 1 h and 6 h of recovery. In the neocortex, HSP 72 was first seen in layer IV, and later also in surviving neurons in layer II. In the CA1 region and in the crest of dentate gyrus, HSP 72 expression was evident in cells adjacent to irreversibly damaged neurons. In the CA3 region and the hilus of dentate gyrus, HSP 72 was expressed in a few scattered neurons. In septal nucleus, HSP 72 was expressed in a lateral to medial fashion over a period of 1-3 days of recovery. We conclude that severe insulin-induced hypoglycemia induces a stress response in neurons in the recovery phase, including inhibition of protein synthesis initiation, depression of eIF-2 activity, and a delayed and prolonged expression of HSP 72 in surviving neurons. The HSP 72 expression may be a protective response to injurious stress.
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| 7. |
- Bergstedt, Kerstin, et al.
(författare)
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Postischaemic changes in protein synthesis in the rat brain : effects of hypothermia
- 1993
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Ingår i: Experimental Brain Research. - 0014-4819. ; 95:1, s. 91-99
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Tidskriftsartikel (refereegranskat)abstract
- Protein synthesis, measured as [14C]-leucine incorporation into proteins, was studied in the normothermic rat brain following 15 min of transient cerebral ischaemia and 1 h, 24 h and 48 h of recirculation, and in the hypothermic (33°C) brain following 1 h and 48 h of recirculation. Ischaemia was induced by bilateral common carotid occlusion combined with hypotension. Following normothermic ischaemia, incorporation of [14C]-leucine was depressed by 40-80% at 1 h of recirculation in all brain regions studied. At 48 h postischaemia, incorporation returned to normal or above normal levels in the inner layers of neocortex, the CA3 region, the striatum and the dentate gyrus, while in the outer layers of neocortex and in the hippocampal CA1 region the incorporation was persistently decreased by 26% and 40% respectively. At 24 and 48 h postischaemia, protein synthesis in the CA1 region and the striatum could be attributed to proliferating microglia. Intra-ischaemic hypothermia ameliorated the persistent depression of protein synthesis in the CA1 region at 48 h postischaemia, and a two-fold increase compared to the normothermic group was observed both in the CA1 region and the striatum. In the cortex, eucaryotic initiation factor 2 activity transiently decreased at 30 min postischaemia. In animals subjected to intra-ischaemic hypothermia, the eucaryotic initiation factor 2 activity was reduced by 50% of control at 30 min of recirculation compared with 77% in normothermic animals. We conclude that the postischaemic depression of protein synthesis is in part caused by a decrease in eucaryotic initiation factor 2 activity. The early postischaemic depression may reflect a reaction of the tissue to stress, while the late persistent depression, which is normalised by intra-ischaemic hypothermia, may be related to the mechanism of cell death.
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| 8. |
- Bice, Annie R., et al.
(författare)
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Homotopic contralesional excitation suppresses spontaneous circuit repair and global network reconnections following ischemic stroke
- 2022
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Ingår i: eLife. - 2050-084X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Understanding circuit-level manipulations that affect the brain’s capacity for plasticity will inform the design of targeted interventions that enhance recovery after stroke. Following stroke, increased contralesional activity (e.g. use of the unaffected limb) can negatively influence recovery, but it is unknown which specific neural connections exert this influence, and to what extent increased contralesional activity affects systems-and molecular-level biomarkers of recovery. Here, we combine optogenetic photostimulation with optical intrinsic signal imaging (OISI) to examine how contralesional excitatory activity affects cortical remodeling after stroke in mice. Following photothrombosis of left primary somatosensory forepaw (S1FP) cortex, mice either recovered spontaneously or received chronic optogenetic excitation of right S1FP over the course of 4 weeks. Contralesional excitation suppressed perilesional S1FP remapping and was associated with abnormal patterns of stimulus-evoked activity in the unaffected limb. This maneuver also prevented the restoration of resting-state functional connectivity (RSFC) within the S1FP network, RSFC in several networks functionally-distinct from somatomotor regions, and resulted in persistent limb-use asymmetry. In stimulated mice, perilesional tissue exhibited transcriptional changes in several genes relevant for recovery. Our results suggest that contralesional excitation impedes local and global circuit reconnection through suppression of cortical activity and several neuroplasticity-related genes after stroke, and highlight the importance of site selection for therapeutic intervention after focal ischemia.
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| 9. |
- Blomqvist, Photjanee, et al.
(författare)
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Cyclic AMP Concentrations in Rat Neocortex and Hippocampus During and Following Incomplete Ischemia : Effects of Central Noradrenergic Neurons, Prostaglandins, and Adenosine
- 1985
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Ingår i: Journal of Neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 44:5, s. 1345-1353
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Tidskriftsartikel (refereegranskat)abstract
- Abstract: The concentrations of cyclic AMP, noradrenaline, glycogen, glucose, lactate, pyruvate, labile phosphate compounds, and free fatty acids were investigated in the rat neocortex and hippocampus during and following cerebral ischemia. An incomplete ischemia of 5 and 15 min duration was induced by bilateral carotid clamping combined with hypotension. The postischemic events were studied after 5, 15, and 60 min of recirculation. Five minutes of ischemia did not significantly alter the neocortical or hippocampal concentrations of cyclic AMP. After 15 min of ischemia the neocortical levels decreased significantly below control values. In the recirculation period following ischemia a significant elevation of the cyclic AMP concentrations was observed. Following 5 min of recirculation after 5 min of ischemia the levels increased from 2.53 ± 0.21 nmol ± g−1 to 5.18 ± 0.09 nmol ± g−1 in the neocortex and from 2.14 ± 0.16 nmol ± g−1 to 3.52 ± 0.35 nmol ± g−1 in the hippocampus. Five minutes of recirculation following 15 min of ischemia led to a significant increase in the levels of cyclic AMP, to 12.86 ± 1.43 nmol ± g−1 in the neocortex to 5.58 ± 0.57 nmol ± g−1 in the hippocampus. With longer recirculation periods the cyclic AMP levels progressively decreased and were similar to control values after 60 min. Depletion of cortical noradrenaline by at least 95% was performed by injections of 6‐hydroxydopamine into the ascending axon bundles from the locus ceruleus. The lesion did not significantly change the ischemic or postischemic neocortical and hippocampal levels of cyclic AMP, glycogen, or free fatty acids including arachidonic acid. Treatment of the animals with theophyllamine (23, 46, and 92 mg ± kg−1) or indomethacin (10 mg ± kg−1) did not affect the postischemic levels of cyclic AMP. It is concluded that central noradrenergic neurons, prostaglandins, and adenosine are not of major importance for the observed postischemic elevations of cyclic AMP and that the changes in the concentrations of free fatty acids measured during and following ischemia are not mediated by noradrenergic neurons.
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| 10. |
- Blomqvist, Photjanee, et al.
(författare)
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Lesions of the locus coeruleus system aggravate ischemic damage in the rat brain
- 1985
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Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940. ; 58:3, s. 353-358
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Tidskriftsartikel (refereegranskat)abstract
- The possibility that the noradrenergic locus coeruleus system influences brain damage following ischemia was explored in rats. Bilateral lesions of the locus coeruleus projections to the forebrain aggravated the neuronal necrosis in the hippocampal CAI region and neocortex following complete cerebral ischemia induced by transient cardiac arrest. These findings provide evidence that the postischemic activation of the inhibitory locus coeruleus system could counteract a possible detrimental neuronal hyperexcitation, thereby limiting neuronal necrosis.
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| 11. |
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| 12. |
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| 13. |
- 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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| 14. |
- 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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| 15. |
- 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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| 16. |
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| 17. |
- Cardell, M., et al.
(författare)
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High resolution immunogold analysis reveals distinct subcellular compartmentation of protein kinase Cγ and δ in rat Purkinje cells
- 1997
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Ingår i: Neuroscience. - 0306-4522. ; 82:3, s. 709-725
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Tidskriftsartikel (refereegranskat)abstract
- High resolution immunogold cytochemistry was used to investigate the subcellular distribution of protein kinase Cγ and δ in Purkinje cells of the rat cerebellum. Postembedding incubation with an antibody raised to a peptide sequence near the C-terminus of protein kinase Cγ resulted in strong labelling along the dendrosomatic plasma membrane. A quantitative analysis indicated that this labelling reflected the existence of two pools of protein kinase Cγ; one membrane associated pool and one cytoplasmic pool located within 50 nm of the plasma membrane. The labelling along the plasma membrane showed a pronounced and abrupt increase when moving from the cell body into the axon initial segment. Gold particles signalling protein kinase Cγ were also enriched in putative Purkinje axon terminals in the dentate nucleus. The only organelle showing a consistent immunolabelling for protein kinase Cγ was the Golgi apparatus where the gold particles were restricted to the trans face. Protein kinase Cγ immunoreactivity also occurred in the Purkinje cell spines, with an enrichment in or near the postsynaptic density. Antibodies to protein kinase Cδ produced a very different labelling pattern in the Purkinje cells. Most of the gold particles were associated with rough endoplasmic reticulum, particularly with those cisternae that were located close to the nucleus or in the nuclear indentations. No significant protein kinase C5 immunolabelling was detected at the plasma membrane or in Purkinje cell spines. The present data point to a highly specific compartmentation of the two major protein kinase C isozyme in Purkinje cells and suggest that these isozymes act on different substrates and hence have different regulatory functions within these neurons.
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| 18. |
- Cardell, Monika, et al.
(författare)
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Protein kinase C is translocated to cell membranes during cerebral ischemia
- 1990
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Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940. ; 119:2, s. 228-232
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Tidskriftsartikel (refereegranskat)abstract
- The subcellular distribution of PKC(α) and PKC(γ) was studied in homogenates of cerebral cortex from rats subjected to 10 and 15 min of ischemia and 15 min of ischemia followed by 1 h, 6 h, 24 h, 48 h, and 7 days of reperfusion. During ischemia no significant changes in the levels of PKC (α) were seen. During the first hour of reperfusion, a transient 2.5-fold (P < 0.05) increase in PKC(α) levels was observed in the particulate fraction. In contrast, a three-fold increase of PKC(γ) in the particulate fraction concomitant with a 40% decrease in the cytosol was noted during ischemia. In the postischemic phase the levels in the cytosol decreased to 35% of control values at 2 days following ischemia, with a concomitant decrease in the particulate fraction to control levels. The redistribution of PKC to the cell membranes during and following ischemia could be due to ischemia induced receptor activation, increased levels of diacylglycerols, arachidonate and intracellular calcium, and may be of importance for the development of ischemic neuronal damage.
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| 19. |
- Cardell, Monika, et al.
(författare)
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Time Course of the Translocation and Inhibition of Protein kinase C During Complete Cerebral Ischemia in the Rat
- 1993
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Ingår i: Journal of Neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 61:4, s. 1308-1314
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Tidskriftsartikel (refereegranskat)abstract
- Abstract: The time course for the ischemia‐induced changes in the subcellular distribution of protein kinase C (PKC) (α), (β311). and (γ) and the activity of PKC were studied in the neocortex of rats subjected to 1, 2, 3, 5, 10, and 15 min of global cerebral ischemia. In the particulate fraction, a 14‐fold increase in PKC (γ) levels was seen at 3 min of ischemia, which further increased at 5–15 min of ischemia. At 15 min of ischemia, PKC (γ) and (βll) levels had increased two‐ and six‐fold, respectively. In the cytosolic fraction, a transient early 1.4‐fold increase in PKC (βll) and PKC (γ) levels was seen, whereas no change in the levels PKC (α) was noted. PKC (γ) levels then progressively declined, reaching 50% at 15 min of ischemia. At 5 min of ischemia, a 43% decrease in PKC activity was seen in the particulate fraction, reaching 50% at 15 min of ischemia concomitant with a 27% decrease in the cytosolic fraction. There was no change in the activator‐independent PKC activity. Pretreatment with the ganglioside AGF2 prevented the redistribution of PKC (γ) in the particulate fraction at 5 min. but not at 10 min of ischemia. The observed time course for the translocation of PKC (γ) parallels the ischemia‐induced release of neurotransmitters and increased levels of diacylglycerols, arachidonate, and intra‐cellular calcium and delineates this subspecies as especially ischemia‐sensitive. Ganglioside pretreatment delayed the translocation of PKC (γ), possibly by counteracting the effects of ischemia‐induced factors that favor PKC binding to cell membranes.
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| 20. |
- Childs, Charmaine, et al.
(författare)
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Report of a consensus meeting on human brain temperature after severe traumatic brain injury : Its measurement and management during pyrexia
- 2010
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Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; NOV
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Tidskriftsartikel (refereegranskat)abstract
- Temperature disturbances are common in patients with severe traumatic brain injury. The possibility of an adaptive, potentially beneficial role for fever in patients with severe brain trauma has been dismissed, but without good justification. Fever might, in some patients, confer benefit. A cadre of clinicians and scientists met to debate the clinically relevant, but often controversial issue about whether raised brain temperature after human traumatic brain injury (TBI) should be regarded as "good or bad" for outcome. The objective was to produce a consensus document of views about current temperature measurement and pyrexia treatment. Lectures were delivered by invited speakers with National and International publication track records in thermoregulation, neuroscience, epidemiology, measurement standards and neurocritical care. Summaries of the lectures and workshop discussions were produced from transcriptions of the lectures and workshop discussions. At the close of meeting, there was agreement on four key issues relevant to modern temperature measurement and management and for undergirding of an evidence-based practice, culminating in a consensus statement. There is no robust scientific data to support the use of hypothermia in patients whose intracranial pressure is controllable using standard therapy. A randomized clinical trial is justified to establish if body cooling for control of pyrexia (to normothermia) vs moderate pyrexia leads to a better patient outcome for TBI patients.
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| 21. |
- 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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| 22. |
- 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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| 23. |
- Coimbra, Cicero, et al.
(författare)
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Moderate hypothermia mitigates neuronal damage in the rat brain when initiated several hours following transient cerebral ischemia
- 1994
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Ingår i: Acta Neuropathologica. - 0001-6322. ; 87:4, s. 325-331
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Tidskriftsartikel (refereegranskat)abstract
- Intraischemic moderate hypothermia generally protects the brain against ischemic cell death, while hypothermia instigated several hours into the reperfusion phase is considered to be less effective. Here we report the effect of hypothermia (32.5°-33.5°C) of 5-h duration, initiated at 2, 6, 12, 24 and 36 h into the recirculation phase following 10 min of transient cerebral ischemia, on ischemic neuronal injury in the hippocampus and striatum of the rat. Hypothermia induced at 2 h, and 6 h postischemia reduces neuronal damage in the entire hippocampal CA1 region by approximately 50%. In the lateral CA1 region hypothermia induced at 12 h postischemia, significantly mitigates necrosis. When initiated at 2 h postischemia, but not later, protection was also observed in the striatum. Hypothermia induced 24 and 36 h postischemia was ineffective. A period of hypothermia of 5 h, initiated 2 h postischemia, was required for marked neuronal protection in the CA1 region, while 3.5-h hypothermia decreased neuronal damage by approximately 10% and 30 min hypothermia was ineffective. The clinical implications of the data are that extended period of hypothermia initiated long into the recovery phase following ischemia may prove beneficial. Hypothermia protects brain regions displaying rapid as well as delayed neuronal damage, and a minimal time of hypothermia is required for effective neuronal protection. Also, strict temperature control for up to 24 h postischemia may be required for proper assessment of the efficacy of cerebro-protective drugs.
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| 24. |
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| 25. |
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