| 1. |
- Bengzon, J, et al.
(författare)
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Regulation of neurotrophin and trkA, trkB and trkC tyrosine kinase receptor messenger RNA expression in kindling
- 1993
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Ingår i: Neuroscience. - 0306-4522. ; 53:2, s. 433-446
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Tidskriftsartikel (refereegranskat)abstract
- Levels of messenger RNA for nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, and the tyrosine kinase receptors trkA, trkB and trkC have been studied using in situ hybridization in the rat brain 2 h and four weeks after kindling-induced seizures. Epileptiform activity evoked by hippocampal stimulation and exceeding 70 s lead to a concomitant and transient increase of brain- derived neurotrophic factor, nerve growth factor, trkB and trkC messenger RNA expression in dentate granule cells after both focal and generalized seizures. Brain-derived neurotrophic factor messenger RNA levels were also increased bilaterally in the CA1-CA3 regions, amygdala and the piriform, entorhinal, perirhinal, retrosplenial and temporal cortices after generalized seizures. The magnitude of the increases was similar throughout the development of kindling and in the fully kindled brain. No changes of trkA messenger RNA were observed. In amygdalar kindling, elevated brain-derived neurotrophic factor messenger RNA levels developed more rapidly in the amygdala-piriform cortex than after stimulation in the hippocampus but changes in the hippocampal formation were only seen in few animals. Intraventricular 6-hydroxydopamine or a bilateral fimbria-fornix lesion did not alter basal expression or seizure-evoked changes in messenger RNA levels for neurotrophins or trk receptors but increased the number of animals exhibiting elevated levels after the first stimulation, probably due to a prolongation of seizure activity. Both in sham-operated and fimbria-fornix-lesioned rats seizure activity caused a marked reduction of neurotrophin-3 messenger RNA levels in dentate granule cells. The results indicate that activation of the brain-derived neurotrophic factor gene, at least in dentate granule cells, is an "all-or-none" type of response and dependent on the duration but not the severity of seizures or the stage of kindling epileptogenesis. Changes in brain-derived neurotrophic factor, nerve growth factor, neurotrophin-3 and trkB and trkC were observed concomitantly in the dentate gyrus, which suggests that seizure activity sets in motion a cascade of genomic events possibly mediated via a common mechanism. Since altered messenger RNA levels outside hippocampus were detected only for brain-derived neurotrophic factor, neurotrophin and trk gene expression in these regions seems to be regulated differently.
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| 2. |
- Brundin, P, et al.
(författare)
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Behavioural effects of human fetal dopamine neurons grafted in a rat model of Parkinson's disease
- 1986
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Ingår i: Experimental Brain Research. - 0014-4819. ; 65:1, s. 40-235
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Tidskriftsartikel (refereegranskat)abstract
- The ventral mesencephalon, containing the developing dopaminergic neurons of the substantia nigra-ventral tegmental region, was obtained from aborted human fetuses of 9-19 weeks of gestation. The tissue was grafted into the striatum of rats previously subjected to a 6-hydroxydopamine lesion of the mesostriatal dopamine pathway. The graft recipients were immunosuppressed by daily injections of Cyclosporin A. Amphetamine-induced motor asymmetry was reduced, and finally totally reversed, only in rats receiving grafts from the 9-week old fetal donor. The fluorescence microscopic analysis revealed large numbers of surviving dopamine neurons, and extensive fiber outgrowth into the host striatum, in these rats. By contrast, rats receiving grafts from 11-19 week old donors had at most only few surviving dopamine neurons. These results indicate that human fetal mesencephalic tissue may be an efficient source of dopamine neurons for functional intracerebral grafting in patients with Parkinson's disease.
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| 3. |
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| 4. |
- Brundin, Patrik, et al.
(författare)
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Human fetal dopamine neurons grafted in a rat model of Parkinson's disease : immunological aspects, spontaneous and drug-induced behaviour, and dopamine release
- 1988
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Ingår i: Experimental Brain Research. - 0014-4819. ; 70:1, s. 192-208
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Tidskriftsartikel (refereegranskat)abstract
- We have used a rat model of Parkinson's disease (PD) to address issues of importance for a future clinical application of dopamine (DA) neuron grafting in patients with PD. Human mesencephalic DA neurons, obtained from 6.5-8 week old fetuses, were found to survive intracerebral cell suspension xenografting to the striatum of rats immunosuppressed with Cyclosporin A. The grafts produced an extensive new DA-containing terminal network in the previously denervated caudate-putamen, and they normalized amphetamine-induced, apomorphine-induced and spontaneous motor asymmetry in rats with unilateral lesions of the mesostriatal DA pathway. Grafts from an 11.5-week old donor exhibited a lower survival rate and smaller functional effects. As assessed with the intracerebral dialysis technique the grafted DA neurons were found to restore spontaneous DA release in the reinnervated host striatum to normal levels. The neurons responded with large increases in extracellular striatal DA levels after the intrastriatal administration of the DA-releasing agent d-amphetamine and the DA-reuptake blocker nomifensine, although not to the same extent as seen in striata with an intact mesostriatal DA system. DA fiber outgrowth from the grafts was dependent on the localization of the graft tissue. Thus, grafts located within the striatum gave rise to an extensive axonal network throughout the whole host striatum, whereas grafted DA neurons localized in the neocortex had their outgrowing fibers confined within the grafts themselves. In contrast to the good graft survival and behavioural effects obtained in immunosuppressed rats, there was no survival, or behavioural effects, of human DA neurons implanted in rats that did not receive immunosuppression. In addition, we found that all the graft recipients were immunized, having formed antibodies against antigens present on human T-cells. This supports the notion that the human neurons grafted to the non-immunosuppressed rats underwent immunological rejection. Based on an estimation of the survival rate and extent of fiber outgrowth from the grafted human fetal DA neurons, we suggest that DA neurons that can be obtained from one fetus may be sufficient to restore significant DA neurotransmission unilaterally, in one putamen, in an immunosuppressed PD patient.
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| 5. |
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| 6. |
- Kalén, P, et al.
(författare)
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Intracerebral microdialysis as a tool to monitor transmitter release from grafted cholinergic and monoaminergic neurons
- 1990
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Ingår i: Journal of Neuroscience Methods. - 0165-0270. ; 34:1-3, s. 15-107
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Tidskriftsartikel (refereegranskat)abstract
- In the present study the microdialysis technique has been used as a tool for the study of functional regulation of intracerebrally grafted cholinergic and monoaminergic neurons as well as for the analysis of graft-host interactions. Fetal noradrenergic, serotonergic, dopaminergic, and cholinergic neurons were transplanted into the hippocampus or striatum previously denervated of their intrinsic monoaminergic or cholinergic afferents. After a few months survival, when the grafts had reinnervated the surrounding target, dialysis probes were implanted into the graft-reinnervated region. Although the graft-derived fiber and terminal density varied substantially from one animal to another the transmitters in the extracellular space were maintained at near-normal levels, not only under baseline conditions, but also during K(+)-induced depolarization, transmitter-selective uptake blockade, and tetrodotoxin. This suggests that the grafted neurons possess efficient autoregulatory properties despite their ectopic location. The results also show that monoamine release in the graft-reinnervated host target is impulse-dependent, and that the neurons are spontaneously functionally active at the synaptic level. Electrical stimulation of the lateral habenula (which has previously been identified as a powerful activator of the intrinsic hippocampal cholinergic and noradrenergic afferents) produced a similar increase in the release of these transmitters in the intact and grafted hippocampi. A complex environmental stimulus, such as handling, induced a consistent increase in acetylcholine but not noradrenaline release in the hippocampus. These findings suggest that grafted cholinergic and noradrenergic neurons can be functionally activated by host brain inputs.
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| 7. |
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| 8. |
- Lindvall, O, et al.
(författare)
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Cell therapy and transplantation in Parkinson's disease
- 2001
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : De Gruyter. - 1434-6621 .- 1437-4331. ; 39:4, s. 356-361
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Tidskriftsartikel (refereegranskat)abstract
- Transplanted human fetal dopamine neurons can reinnervate the striatum in patients with Parkinson's disease (PD). Recent findings using positron emission tomography indicate that the grafts are functionally integrated and restore dopamine release in the patient's striatum. The grafts can exhibit long-term survival without immunological rejection and despite an ongoing disease process and continuous antiparkinsonian drug treatment. In the most successful cases, patients have been able to withdraw L-dopa treatment after transplantation and resume an independent life. About two-thirds of grafted patients have shown clinically useful, partial recovery of motor function. The major obstacle for the further development of this cell replacement strategy is that large amounts of human fetal mesencephalic tissue are needed for therapeutic effects. Stem cells hold promise as a virtually unlimited source of self-renewing progenitors for transplantation. The possibility to generate dopamine neurons from such cells is now being explored using different approaches. However, so far the generated neurons have survived poorly after transplantation in animals.
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| 9. |
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| 10. |
- Austrell, Per Erik, et al.
(författare)
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Development of an extremely fatigue-resistant Shock Absorber
- 2014
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Ingår i: Kgk: Kautschuk Gummi Kunststoffe. - 0948-3276. ; 67:11-12, s. 24-31
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Tidskriftsartikel (refereegranskat)abstract
- An extremely fatigue resistant shock absorber was developed from basic mechanics principles using nonlinear elastic material models and finite element analysis. Prototypes were manufactured and tested to confirm the calculations and to find out the fatigue properties. The rubber body fills a cavity at gradually increasing compression. This idea has some clear advantages: A large part of the rubber body is protected against accidental external influences and it is backed up during the deformation by the cavity walls. Also, the stress in the rubber body becomes evenly distributed as only compressive stress is developed in it. The prototypes were tested in nearly 6 million cycles with no visible defects.
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