| 1. |
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| 2. |
- Johansson, Veronica, et al.
(författare)
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Beyond Blind Optimism and Unfounded Fears : Deep Brain Stimulation for Treatment Resistant Depression
- 2013
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Ingår i: Neuroethics. - : Springer Science and Business Media LLC. - 1874-5504 .- 1874-5490. ; 6:3, s. 457-471
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Tidskriftsartikel (refereegranskat)abstract
- The introduction of new medical treatments based on invasive technologies has often been surrounded by both hopes and fears. Hope, since a new intervention can create new opportunities either in terms of providing a cure for the disease or impairment at hand; or as alleviation of symptoms. Fear, since an invasive treatment involving implanting a medical device can result in unknown complications such as hardware failure and undesirable medical consequences. However, hopes and fears may also arise due to the cultural embeddedness of technology, where a therapy due to ethical, social, political and religious concerns could be perceived as either a blessing or a threat. While Deep Brain Stimulation (DBS) for treatment resistant depression (TRD) is still in its cradle, it is important to be proactive and try to scrutinize both surfacing hopes and fears. Patients will not benefit if a promising treatment is banned or avoided due to unfounded fears, nor will they benefit if DBS is used without scrutinizing the arguments which call for caution. Hence blind optimism is equally troublesome. We suggest that specificity, both in terms of a detailed account of relevant scientific concerns as well as ethical considerations, could be a way to analyse expressed concerns regarding DBS for TRD. This approach is particularly fruitful when applied to hopes and fears evoked by DBS for TRD, since it can reveal if our comprehension of DBS for TRD suffer from various biases which may remain unnoticed at first glance. We suggest that such biases exist, albeit a further analysis is needed to explore this issue in full.
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| 3. |
- Johansson, Veronica, et al.
(författare)
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Thinking Ahead on Deep Brain Stimulation: An Analysis of the Ethical Implications of a Developing Technology.
- 2014
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Ingår i: AJOB Neuroscience. - : Informa UK Limited. - 2150-7740 .- 2150-7759. ; 5:1, s. 24-33
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Tidskriftsartikel (refereegranskat)abstract
- Deep brain stimulation (DBS) is a developing technology. New generations of DBS technology are already in the pipeline, yet this particular fact has been largely ignored among ethicists interested in DBS. Focusing only on ethical concerns raised by the current DBS technology is, albeit necessary, not sufficient. Since current bioethical concerns raised by a specific technology could be quite different from the concerns it will raise a couple of years ahead, an ethical analysis should be sensitive to such alterations, or it could end up with results that soon become dated. The goal of this analysis is to address these changing bioethical concerns, to think ahead on upcoming and future DBS concerns both in terms of a changing technology and changing moral attitudes. By employing the distinction between inherent and noninherent bioethical concerns we identify and make explicit the particular limits and potentials for change within each category, respectively, including how present and upcoming bioethical concerns regarding DBS emerge and become obsolete. Many of the currently identified ethical problems with DBS, such as stimulation-induced mania, are a result of suboptimal technology. These challenges could be addressed by technical advances, while for instance perceptions of an altered body image caused by the mere awareness of having an implant may not. Other concerns will not emerge until the technology has become sophisticated enough for new uses to be realized, such as concerns on DBS for enhancement purposes. As a part of the present analysis, concerns regarding authenticity are used as an example.
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| 4. |
- Karlsson, Martin, et al.
(författare)
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Polystyrene replicas of neuronal basal lamina act as excellent guides for regenerating neurites.
- 2011
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1878-7568 .- 1742-7061. ; 7, s. 2910-2918
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Tidskriftsartikel (refereegranskat)abstract
- Various scaffolds, natural or artificial, have been used for neural repair, including basal lamina scaffolds obtained through extraction of nerves. Here we tested whether plastic casts of such preparations could be used for neurite guidance. To this end, longitudinal micron thick sections of rat sciatic nerve were extracted with detergents and treated with Dnase, yielding an acellular basal lamina master. From the basal lamina master a polydimethylsiloxane (PDMS) mold was made. Then a polystyrene replica was made using the PDMS mold as the master. The polystyrene replica showed high similarity to the master within nanometer resolution as revealed by scanning electron microscopy. Organ cultured mouse dorsal root ganglia grown on the polystyrene replica and the master preparation exhibited guided outgrowth of neurites as assayed by two-dimensional fast Fourier transform analysis on preparations, where the neurites had been visualized by β-III-tubulin staining. The neurites aligned longitudally in the direction of the original basal lamina tubes. Thus, using inexpensive methods it is possible to make replicas of basal lamina which can be used for neurite guidance. This opens a new avenue for nerve reconstruction.
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| 5. |
- Kvist, Martin, et al.
(författare)
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Costimulation blockade in transplantation of nerve allografts: long-term effects.
- 2008
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Ingår i: Journal of the Peripheral Nervous System. - : Wiley. - 1529-8027 .- 1085-9489. ; 13:3, s. 200-207
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Tidskriftsartikel (refereegranskat)abstract
- Costimulation blockade can prevent rejection of nerve allografts in short-term studies. We tested if costimulation blockade also prevented rejection of nerve allografts in long-term experiments, thereby improving functional recovery. A 7-mm sciatic nerve defect in C57/BL6 mice was bridged either by nerve allografts from Balb/C mice or by isogenic nerve grafts (isografts) from C57/BL6 mice. Costimulation blockade in the form of a triple treatment with anti-LFA-1, anti-CD40L, and CTLA4Ig was given at post-operative days 0, 2, 4, and 6 (intraperitoneal). Control mice (placebo; allografts) with nerve grafts were treated with isotype antibodies during the same time period. After 49 days, tetanic muscle force, wet weight of gastrocnemius muscle, histology, and morphometry in the tibial nerve were evaluated. Costimulation blockade diminished rejection of the nerve allografts. Axons bridged the graft. Treatment increased wet weight of the gastrocnemius muscle and resulted in a higher mean myelin area/nerve fiber in the tibial nerve distal to the nerve grafts. Tetanic muscle force and number of axons in tibial nerve showed no differences between groups. We conclude that rejection is suppressed by costimulation blockade. Treatment improves recovery of target muscle and myelination after nerve allografting.
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| 6. |
- Kvist, Martin, et al.
(författare)
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Immunomodulation by costimulation blockade inhibits rejection of nerve allografts
- 2007
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Ingår i: Journal of the Peripheral Nervous System. - : Wiley. - 1085-9489 .- 1529-8027. ; 12:2, s. 83-90
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate if costimulation blockade could be used to modulate the immune response, to prevent rejection, and to stimulate regeneration into nerve allografts. Nerve allografts from Balb/C mice, and isogenic nerve grafts (isografts) from C57/BL6 mice, were used to bridge a 7-mm gap of the sciatic nerve in C57/BL6 mice. Allograft recipients were treated with either a triple treatment with anti-lymphocyte function antigen-1 (anti-LFA), anti-CD40 ligand (anti-CD40L), and cytotoxic T-lymphocyte antigen 4 immunoglobulin (anti-CTLA4Ig) or isotype antibodies (placebo) at postoperative days 0, 2, 4, and 6 (intraperitoneal). After 5 or 9 days, the nerve grafts, together with the proximal and the distal nerve segments, were evaluated by histology and immunocytochemistry for inflammatory cells [CD4-positive (CD4+) and CD8-positive (CD8+) staining cells] and axonal outgrowth (neurofilaments). The immune response was inhibited by costimulation blockade with less extensive inflammation and a lower number of CD4+ staining cells in triple-treated allografts at 9 days. The regeneration rate was significantly faster in isografts (0.75 mm/day) compared with allografts with placebo treatment (0.39 mm/day), but not when compared with triple-treated allografts (0.49 mm/day). At 9 days, the axons were significantly longer in nerve isografts than in nerve allografts, irrespective of treatment. Hence, costimulation blockade neither increased the regeneration rate nor the outgrowth length in triple-treated allografts. We conclude that costimulation blockade inhibits the immune response in nerve allografts without deterring early axonal outgrowth.
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| 7. |
- Kvist, Martin, et al.
(författare)
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Regeneration in, and properties of, extracted peripheral nerve allografts and xenografts.
- 2011
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Ingår i: Journal of Plastic Surgery and Hand Surgery. - 2000-656X .- 2000-6764. ; 45:3, s. 122-128
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Tidskriftsartikel (refereegranskat)abstract
- Abstract When not enough conventional autologous nerve grafts are available, alternatives are needed to bridge nerve defects. Our aim was to study regeneration of nerves in chemically-extracted acellular nerve grafts from frogs, mice, humans (fresh and stored sural nerve), pigs and rats when defects in rat sciatic nerves were bridged. Secondly, we compared two different extraction procedures (techniques described by Sondell et al. and Hudson et al.) with respect to how efficiently they supported axonal outgrowth, and remaining laminin and myelin basic protein (MBP), after extraction. Isografts (rat) and xenografts (mouse) were transplanted into defects in rat sciatic nerves. Acellular nerve allografts from rats, extracted by the Sondell et al's technique, had an appreciably longer axonal outgrowth based on immunohistochemical staining of neurofilaments, than acellular nerve xenografts except those from the pig. Among acellular xenografts there was considerably longer axonal outgrowth in the grafts from pigs compared with those from humans (fresh), but there were no other differences among the xenografts with respect to axonal outgrowth. Axonal outgrowth in acellular nerve xenografts from mice, extracted by the method described by Sondell et al. was longer than in those extracted by Hudson et al's method, while there was no difference in outgrowth between extracted nerve isografts from rats. Electrophoretic analysis of extracted acellular nerve grafts showed remaining laminin, but not MBP, after both extraction procedures. These preserved laminin and removed MBP in acellular nerve grafts. Such grafts can be used to reconstruct short defects in nerves irrespective of their origin. However, selecting and matching a suitable combination of graft and host species may improve axonal outgrowth.
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| 8. |
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| 9. |
- Arai, Takeru, et al.
(författare)
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Axonal outgrowth in muscle grafts made acellular by chemical extraction
- 2000
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Ingår i: Restorative Neurology and Neuroscience. - 0922-6028. ; 17:4, s. 165-174
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To compare nerve regeneration in autologous detergent extracted and freeze-thawed muscle grafts and to electrophoretically characterize the grafts. Methods: Autologous acellular muscle grafts were created either by freeze/thawing or by detergent extraction and then used to bridge a 10 mm gap in rat sciatic nerve. The autologous grafts were compared with respect to protein content, using electrophoresis preimplantation, and axonal outgrowth, Schwann cell and macrophage content, using immunocytochemistry (neurofilaments, S-100 protein, ED 1 macrophages) at 5-20 days postimplantation. Results: The extracted muscle grafts were elastic, but the amount of several proteins was reduced and laminin was still present at a position of basal laminae of the muscle fibers. The freeze/thawed grafts were brittle and lacked elasticity, but resulted in minor changes in major proteins. The axons regenerated through both types of grafts (initial delay 6 days and rate 0.7-0.8 mm/day), which shrunk in length by 25 %. There were no apparent differences with respect to Schwann cells and macrophages. Conclusions: The results suggest that detergent extracted mucle tissue, in which some basal lamina proteins remain but cells are removed, could present a new favourable option for nerve grafting.
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| 10. |
- Bergmark, Maria, et al.
(författare)
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Experimental nerve compression and upregulation of CPON in DRG
- 2001
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Ingår i: NeuroReport. - 1473-558X. ; 12:17, s. 3783-3786
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Tidskriftsartikel (refereegranskat)abstract
- Expression of C-terminal flanking peptide of neuropeptide Y (CPON) in DRG and cell proliferation (incorporation of BrdU) in sciatic nerve of rats following chronic nerve compression (silicone tubes with different internal diameters) was studied by immunocytochemistry. An increased number of CPON-positive neurons and cells incorporating BrdU was induced on the compressed side, most pronounced when a tight tube was used, while no cells expressed CPON or BrdU in intact nerves. The increase was transient and declined with time. Nerve compression induces transient cell proliferation in the nerve and expression of CPON in nerve cell bodies, but this is of a lesser magnitude than those following nerve transection.
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