| 1. |
- Boer, GJ, et al.
(författare)
-
Clinical neurotransplantation: Core assessment protocol rather than sham surgery as control
- 2002
-
Ingår i: Brain Research Bulletin. - 0361-9230. ; 58:6, s. 547-553
-
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.
|
|
| 2. |
- Petersén, Åsa, et al.
(författare)
-
Brain-derived neurotrophic factor inhibits apoptosis and dopamine-induced free radical production in striatal neurons but does not prevent cell death
- 2001
-
Ingår i: Brain Research Bulletin. - 0361-9230. ; 56:3-4, s. 331-335
-
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.
|
|
| 3. |
- Risedal, Anette, et al.
(författare)
-
Environmental influences on functional outcome after a cortical infarct in the rat.
- 2002
-
Ingår i: Brain Research Bulletin. - 0361-9230 .- 1873-2747. ; 58:3, s. 315-321
-
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.
|
|
| 4. |
- Tarkowski, E, et al.
(författare)
-
Cerebral pattern of pro- and anti-inflammatory cytokines in dementias
- 2003
-
Ingår i: Brain Research Bulletin. - 0361-9230. ; 61:3, s. 255-260
-
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.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Grillner, S
(författare)
-
From egg to action
- 2000
-
Ingår i: Brain research bulletin. - : Elsevier BV. - 0361-9230. ; 53:5, s. 473-477
-
Tidskriftsartikel (refereegranskat)
|
|
| 10. |
|
|
