| 1. |
- Boer, GJ, et al.
(författare)
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Clinical neurotransplantation: Core assessment protocol rather than sham surgery as control
- 2002
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Ingår i: Brain Research Bulletin. - 0361-9230. ; 58:6, s. 547-553
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Forskningsöversikt (refereegranskat)abstract
- Basic neurotransplantation research evoked clinical trials of restorative brain surgery. Parkinson's disease was the first and primary test bed for this putative new therapeutic method. Various centers performed the grafting surgery and the behavioral evaluations in different ways, and observed a varying degree of symptomatic relief. This led to a plea for double blind placebo-controlled clinical trials, which have since been performed and of which the first outcomes were recently published. In the present paper this approach of experimental neurotransplantation in brain diseases is discussed and rejected. Neural grafting in the central nervous system is irreversible and is therefore not suitable for experimental approaches originally designed for and best suited to drug studies. For Parkinson's disease in particular, the technique is far from optimized to perform large-scale studies at this stage. Moreover, previous negative results of adrenal medulla tissue implantation in the brain of patients make placebo effects rather unlikely. Moral arguments concerning the validity of the informed consent, therapeutic misconception, and the risk/benefit ratio can be added in the plea against this control surgery. Finally, a recommendation is made for study designs that apply a disease-dedicated core assessment protocol (CAP) that can evaluate the period from pre-operative to post-convalescent stages quantitatively, and therefore, unbiased. The strength of these CAPs is that they allow comparisons of different grafting techniques, of results between centers and of other types of interventions and invasive treatments such as deep brain stimulation. On ethical grounds, it is unacceptable not to use a study design that circumvents sham or imitation surgery. It is a challenge for the neuroscience community to develop CAPs for brain diseases that are eligible for neurotransplantation in the future. (C) 2002 Elsevier Science Inc. All rights reserved.
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| 2. |
- Larsson, L C, et al.
(författare)
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Discordant xenografts : different outcome after mouse and rat neural tissue transplantation to guinea-pigs
- 1999
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Ingår i: Brain Research Bulletin. - 0361-9230. ; 49:5, s. 76-367
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Tidskriftsartikel (refereegranskat)abstract
- Embryonic neural tissue obtained from other species has been considered as a donor tissue source in repair strategies for human neurodegenerative disorders. The neuro- and immunobiology of distantly related species combinations, discordant xenografts, need to be characterised. For this purpose, a small animal model would be an important research tool. Adult guinea-pigs, and adult rats as controls, received intrastriatal grafts of either mouse or rat embryonic ventral mesencephalic tissue. The survival rates and types of host immune response were assessed at 2 weeks after grafting using stereological techniques and semi-quantitative evaluations. In the mouse-to-guinea-pig group, all transplants were rejected and no tyrosine hydroxylase-immuno reactive (TH-IR) cells remained. In the rat-to-guinea-pig group, there was good survival of TH-IR cells (5050 SEM+/-1550), similar to that in the rat-to-rat group (4900 SEM+/-1540). In the mouse-to-rat group, half of the animals had no surviving TH-IR cells (520 SEM+/-230 for the whole group). These species combinations offer inexpensive, efficient, and suitable conditions to study important survival factors for discordant xenogeneic neural tissue transplants. The factors responsible for the divergent graft outcomes between the two combinations might provide clues on how to manipulate xenogeneic tissue to increase survival rates in the future.
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| 3. |
- Petersén, Åsa, et al.
(författare)
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Brain-derived neurotrophic factor inhibits apoptosis and dopamine-induced free radical production in striatal neurons but does not prevent cell death
- 2001
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Ingår i: Brain Research Bulletin. - 0361-9230. ; 56:3-4, s. 331-335
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Tidskriftsartikel (refereegranskat)abstract
- In hereditary Huntington's disease, a triplet repeat disease, there is extensive loss of striatal neurons. It has been shown that brain-derived neurotrophic factor (BDNF) protects striatal neurons against a variety of insults. We confirmed that BDNF enhances survival and DARPP-32 expression in primary striatal cultures derived from postnatal mice. Furthermore, BDNF inhibited intracellular oxyradical stress triggered by dopamine, and partially blocked basal and dopamine-induced apoptosis. Nevertheless, BDNF failed to rescue striatal neurons from dopamine-induced cell death. Therefore, BDNF inhibits free radical and apoptotic pathways in medium spiny neurons, but does so downstream from the point of commitment to cell death.
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| 4. |
- Risedal, Anette, et al.
(författare)
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Environmental influences on functional outcome after a cortical infarct in the rat.
- 2002
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Ingår i: Brain Research Bulletin. - 0361-9230 .- 1873-2747. ; 58:3, s. 315-321
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Tidskriftsartikel (refereegranskat)abstract
- The effect of postoperative housing conditions on functional outcome and brain-derived neurotrophic factor (BDNF) gene expression was evaluated 1 month after a distal ligation of the right middle cerebral artery (MCA) in spontaneously hypertensive rats. Two days postoperatively the rats were randomized into four groups; individually housed with no equipment (deprived group), individually housed with free access to a connected running wheel (running group), housed together in a large cage with no equipment (social group) or in the same size of cage furnished with bars, chains and various things to manipulate (enriched group). The enriched rats had significantly higher scores when crossing a rotating horizontal rod than deprived and running rats. The social group performed significantly better than the deprived group. The BDNF gene expression in the ipsi- and contralateral cortex, thalamus, hippocampus and cerebellum did not significantly differ between the groups. The weight of the adrenal glands was significantly increased in running rats suggesting that postischemic running may be stressful. We conclude that the beneficial effect of postischemic environmental enrichment is likely to be a combination of social and various physical activities, and that BDNF gene expression 1 month after a cortical infarct did not correlate with functional outcome.
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| 5. |
- Sahlin, C, et al.
(författare)
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Changes in contractile response and effect of a calcium antagonist, nimodipine, in isolated intracranial arteries of baboon following experimental subarachnoid hemorrhage
- 1990
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Ingår i: Brain Research Bulletin. - 0361-9230. ; 24:3, s. 355-361
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Tidskriftsartikel (refereegranskat)abstract
- Isolated pial arteries from a previously well-characterized model of experimental subarachnoid hemorrhage (SAH) in baboon were tested for their contractile response to 5-hydroxytryptamine (5-HT), norepinephrine (NE), and prostaglandin F2 alpha (PGF2 alpha) and the effect of the calcium antagonist, nimodipine. Autologous blood was injected cisternally at three times with one-day intervals to a total amount of 11.5-29.5 ml (mean: 18.5 ml), and the animals were killed 7 days after the first injection. Untreated animals served as controls. The degree of maximum contraction (EAm) with 5-HT and NE in the control situation was for the three arteries tested in the order middle cerebral greater than anterior cerebral greater than basilar artery. Experimental SAH markedly increased EAm, by 190-370 percent above control values (depending on type of vessel) for 5-HT and 170-185 percent for NE. In addition, the sensitivity to 5-HT was significantly increased, as evidenced by a left-shift of the concentration-response curve. Previous exposure of the artery to 10(-6) M nimodipine reduced the contractile response of both amines to approximately half, the inhibition being slightly less pronounced post-SAH. When vessels were contracted beforehand with the amines or with PGF2 alpha, followed by administration of increasing amount of nimodipine (10(-9) M to 10(-6) M), a concentration-dependent relaxation was obtained by up to 60 percent of the original level. This relaxing effect was significantly less following SAH in the experiments with NE and PGF2 alpha compared to 5-HT; the contraction in the presence of 5-HT did not differ before and after experimental SAH. The experiments show that SAH markedly enhances the intrinsic activity for both 5-HT and NE. Nimodipine inhibits the contractile response less efficiently following experimental SAH. The difference in the responsiveness to 5-HT on the one hand, and to NE and PGF2 alpha on the other, could be due to differences in the blood-induced alterations of those calcium channels that are influenced by the calcium antagonist, nimodipine.
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| 6. |
- Tarkowski, E, et al.
(författare)
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Cerebral pattern of pro- and anti-inflammatory cytokines in dementias
- 2003
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Ingår i: Brain Research Bulletin. - 0361-9230. ; 61:3, s. 255-260
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Tidskriftsartikel (refereegranskat)abstract
- The knowledge regarding putative inflammatory component(s) participating in Alzheimer's disease (AD) and vascular dementia (VAD) is scarce. Recently, we have demonstrated the presence of certain inflammatory cytokines in the cerebrospinal fluid (CSF) of demented patients. Although the initial event(s) triggering the neurodegenerative processes in AD versus VAD may be different and lead to different neuropathological changes, it may initiate a similar cascade of cytokine production in response to neuronal injury. The cytokines released in the central nervous system (CNS) may, in turn, act in a similar manner in both diseases, amplifying some pathological changes such as amyloidogenesis and white matter lesions or on the contrary acting as neuroprotective molecules. This review will focus on the intracerebral production of the pro- and anti-inflammatory cytokines interleukin IL-1beta, IL-1 receptor antagonist (IL-1ra), IL-6 and TNF-alpha in dementia, and their relation to gene polymorphism, to cerebral neuronal damage, apoptosis, and to clinical variables of dementia. Our results, which show for the first time strikingly increased CSF levels of TNF-alpha but not of TNF-beta, IL-1beta or IL-6 in AD and VAD, may form a conceptual framework for further studies of neuroprotective mechanisms in dementias. (C) 2003 Elsevier Science Inc. All rights reserved.
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| 7. |
- Zeng, J, et al.
(författare)
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Are neuronal markers and neocortical graft-host interface influenced by housing conditions in rats with cortical infarct cavity?
- 1999
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Ingår i: Brain Research Bulletin. - 0361-9230. ; 48:2, s. 165-171
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to study if exposure to an enriched environment influenced graft-host interface and neuronal markers in neocortical grafts implanted in cortical infarct cavities 3 weeks after distal ligation of the middle cerebral artery in adult hypertensive rats. Half the rats were exposed to an enriched environment for 2 h daily 5 days a week starting 1 week after the arterial ligation. The brain was fixed by perfusion 4 weeks postgrafting. The immunoreactivity to glial fibrillary acidic protein, microtubule associated protein 2, and synaptophysin was studied in coronal paraffin-embedded sections. A distinct glial border separated the infarct cavity from the surrounding brain in sham-transplanted rats. Most grafts filled the larger part of the infarct cavity. In 8 of 18 transplants, 4 in each experimental group, part of the transplants protruded through the thin glial membrane that delineated the transplant-host interface into the adjacent host brain tissue. Microtubule associated protein 2 immunostained sections indicated bridging of dendrites in the host-transplant interface. Synaptophysin immunoreactivity was significantly higher in grafts than in contralateral cortex. However, graft morphology and neuronal marker immunoreactivity did not differ between rats housed in standard and activity stimulating cages.
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| 8. |
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| 9. |
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| 10. |
- Bergenius, J., et al.
(författare)
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The subjective horizontal at different angles of roll-tilt in patients with unilateral vestibular impairment
- 1996
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Ingår i: Brain Research Bulletin. - : Elsevier BV. - 0361-9230 .- 1873-2747. ; 40:5-6, s. 385-390
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Tidskriftsartikel (refereegranskat)abstract
- The subjective visual horizontal is mainly dependent on the otolithic system. A group of 11 patients with sudden unilateral vestibular impairment were asked to set a dimly illuminated bar according to their subjective horizontal when they were seated upright and tilted 10, 20, and 30 degrees to the right and left in a completely darkened room (Bias test). The patients were examined within 1 week, after 3 and 6 weeks, and 9 patients consented to the 11-week follow-up. The results were compared with ENG examinations. In the acute stage of the disease all patients, when they were in upright position, set the light bar tilted towards the affected side. At roll tilt to the affected side, 9 of the 11 patients set the light bar in the same direction as their body tilt (undercorrection). At a tilt to the unaffected side 6 of the 11 patients made an undercorrection. For the group of patients the magnitude of undercorrection was larger at tilt to the affected side than to the unaffected side. The patients' ability to correctly align the light bar with the true horizontal gradually improved but was found normal in both upright and tilted positions in only three of the nine patients at the last follow-up. In four of the six patients who still demonstrated pathologic results, these were met only in tilted positions. No significant correlation was found between the intensity of spontaneous nystagmus or the degree of caloric side difference and the deviation in setting of the light bar in upright or tilted positions. The large asymmetric perceptual responses at tilt found at onset might be explained by the two-directional organisation of the utricle.
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