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- Eriksson Linsmeier, Cecilia, et al.
(författare)
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Can histology solve the riddle of non-functioning electrodes; factors influencing the biocompatibillity of brain machine interfaces.
- 2011
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Ingår i: Progress in Brain Research. - 0079-6123. ; 194, s. 181-189
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Bokkapitel (refereegranskat)abstract
- Neural interfaces hold great promise to become invaluable clinical and diagnostic tools in the near future. However, the biocompatibility and the long-term stability of the implanted interfaces are far from optimized. There are several factors that need to be addressed and standardized when improving the long-term success of an implanted electrode. We have chosen to focus on three key factors when evaluating the evoked tissue responses after electrode implantation into the brain: implant size, fixation mode, and evaluation period. Further, we show results from an ultrathin multichannel wire electrode that has been implanted in the rat cerebral cortex for 1 year. To improve biocompatibility of implanted electrodes, we would like to suggest that free-floating, very small, flexible, and, in time, wireless electrodes would elicit a diminished cell encapsulation. We would also like to suggest standardized methods for the electrode design, the electrode implantation method, and the analyses of cell reactions after implantation into the CNS in order to improve the long-term success of implanted neural interfaces.
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| 4. |
- Eriksson Linsmeier, Cecilia, et al.
(författare)
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Nanowire Biocompatibility in the Brain - Looking for a Needle in a 3D Stack.
- 2009
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Ingår i: Nano Letters. - : American Chemical Society (ACS). - 1530-6992 .- 1530-6984. ; 9:12, s. 4184-4190
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the brain-tissue response to nanowire implantations in the rat striatum after 1, 6, and 12 weeks using immunohistochemistry. The nanowires could be visualized in the scar by confocal microscopy (through the scattered laser light). For the nanowire-implanted animals, there is a significant astrocyte response at week 1 compared to controls. The nanowires are phagocytized by ED1 positive microglia, and some of them are degraded and/or transported away from the brain.
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- Eriksson Linsmeier, Cecilia
(författare)
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Neuronal and glial differentiation of expanded neural stem and progenitor cells; in vitro and after transplantation.
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis we have used cells dissected from the lateral ganglionic eminence (LGE), the medial ganglionic eminence (MGE), and the cortical primordium of the embryonic mouse forebrain. The tissue was dissected from either i) wild-type mice, ii) green fluorescent protein (GFP)-, or iii) Gtv-a-expressing transgenic mice, and subsequently grown and expanded in vitro using two different protocols. Cells were either plated and extensively expanded as attached glial cultures in the presence of epidermal growth factor (EGF) and serum, or expanded in the presence of EGF and basic fibroblast growth factor (bFGF) as free-floating aggregates termed neurospheres. The attached LGE-derived cells were expanded for more that 7 months (25 passages), and the cells expressed neural stem-/progenitor markers, such as glial fibrillary acidic protein (GFAP), nestin, RC2 and M2/M6, both at early and late passages. We demonstrated that the repeatedly passaged attached glial cultures derived from either the LGE or MGE (but not the cortical primordium) were capable of generating significant numbers of neurons and glial cells at differentiating conditions, i.e. after removal of EGF and serum from the expansion medium. By using a transgenic approach, we were able to show that at least a subset of the newly generated neurons and oligodendrocytes were derived from GFAP-expressing cells. Interestingly, the newly generated neurons were found to retain some of their region-specific expression even after extensive in vitro-expansion. After grafting of the expanded attached LGE-derived cells, we found that they were able to integrate into both the adult (intact and lesioned) and neonatal rat striatum, as visualized with the mouse-specific astroglial marker M2. However, even though these cells had the capacity to differentiate into neurons and glial cells in vitro, we were only able to detect few neuron-like cells after transplantation. Instead these cells expressed almost exclusively an astroglial phenotype after implantation. Moreover, we showed that cells from expanded neurosphere cultures, derived from the LGE, MGE and cortical primordium of the embryonic GFP-transgenic mouse, had the capacity to differentiate into morphologically fully mature neurons, as well as astrocytes and oligodendrocytes after transplantation, as visualized with the species-specific marker M2 and the reporter gene GFP. These results demonstrated the ability of mouse derived neural stem-/progenitor cells expanded in vitro as neurospheres to generate both neurons and glia after transplantation into neonatal recipients, and differentiate into mature neurons with morphological features characteristic for each target site. Altogether, the results of the present thesis demonstrate a capacity of cells derived from the mouse embryonic forebrain to be long-term expanded using two different protocols, and that the cells have the potential to differentiate in vitro and give rise to progeny with at least some region-specific characteristics retained. The cells can also survive and integrate into the host tissue after transplantation. However, mainly cells grown as neurospheres displayed the potential of neuronal differentiation after implantation into the neonatal graft host. A lot of experimental work is still needed in order to understand and control the mechanisms for growth and differentiation of neural stem-/progenitor cells before such cells can be applied in other studies, such as in clinical trials towards treatment of for example neurodegenerative disorders.
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| 6. |
- Eriksson Linsmeier, Cecilia, et al.
(författare)
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Neuronal and glial differentiation within expanded glial cultures derived from the lateral and medial ganglionic eminences.
- 2003
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 184:2, s. 1058-1063
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Tidskriftsartikel (refereegranskat)abstract
- Attached glial-like cell cultures were established from the lateral and medial ganglionic eminences (LGE and MGE) and from the neocortex (Cx) of E13.5 mouse embryos, and expanded over four to five passages under epidermal growth factor (EGF) stimulation. Following removal of EGF and serum, we analysed the generation of neurons and glial cells within the cultures. Significant numbers of βIII-tubulin-positive neurons were generated in both the LGE (about 7% of total cell numbers) and the MGE (around 2%). However, only few βIII-tubulin-positive cells with neuronal morphologies were detected in the differentiated Cx cultures. The newly formed neurons were to a large extent GABAergic, and many of the MGE-derived, but not the LGE-derived, cells expressed the MGE-marker NKX2.1. Most cells in all cultures still appeared astroglial-like, expressing glial fibrillary acidic protein (GFAP), but in addition, CNPase-positive cells with oligodendroglial morphologies were present in the MGE (0.68%), and, to a lesser extent (0.2%), in the LGE cultures. The present results demonstrate that cells of expanded glial cultures from both the LGE and MGE can give rise to significant and, to a certain extent, region-specific neuronal and glial cell types under differentiating conditions.
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| 7. |
- Eriksson Linsmeier, Cecilia, et al.
(författare)
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Neuronal differentiation following transplantation of expanded mouse neurosphere cultures derived from different embryonic forebrain regions.
- 2003
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Ingår i: Experimental Neurology. - 0014-4886. ; 184:2, s. 615-635
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Tidskriftsartikel (refereegranskat)abstract
- In vitro, expanded neurospheres exhibit multipotent properties and can differentiate into neurons, astrocytes and oligodendrocytes. In vivo, cells from neurospheres derived from mouse fetal forebrain have previously been reported to predominantly differentiate into glial cells, and not into neurons. Here we isolated stem/progenitor cells from E13.5 lateral ganglionic eminence (LGE), medial ganglionic eminence (MGE) and cortical primordium, of a green fluorescent protein (GFP)-actin transgenic mouse. Free-floating neurospheres were expanded in the presence of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) and implanted after five to six passages into the striatum, hippocampus and cortex of neonatal rats. Cell suspensions of primary LGE tissue were prepared and grafted in parallel. Grafted cells derived from the primary tissue displayed widespread incorporation into all regions, as visualized with the mouse-specific antibody M2, or mouse satellite DNA in situ hybridization, and differentiated into both neurons, astrocytes and oligodendrocytes. Grafts of neurosphere cells derived from the LGE, MGE and cortical primordium differentiated primarily into astrocytes, but contained low but significant numbers of GFP-immunoreactive neurons. Neurons derived from LGE neurospheres were of three types: cells with the morphology of medium-sized densely spiny projection neurons in the striatum; cells with interneuron-like morphologies in striatum, cortex and hippocampus; and cells integrating into SVZ and migrating along the RMS to the olfactory bulb. MGE- or cortical primordium-derived neurospheres differentiated into interneuron-like cells in both striatum and hippocampus. The results demonstrate the ability of in vitro expanded neural stem/progenitor cells to generate both neurons and glia after transplantation into neonatal recipients, and differentiate in a region-specific manner into mature neurons with morphological features characteristic for each target site.
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| 8. |
- Eriksson Linsmeier, Cecilia, et al.
(författare)
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Soft tissue reactions evoked by implanted gallium phosphide.
- 2008
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Ingår i: Biomaterials. - : Elsevier BV. - 1878-5905 .- 0142-9612. ; 29:35, s. 4598-4604
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Tidskriftsartikel (refereegranskat)abstract
- Neural devices may play an important role in the diagnosis and therapy of several clinical conditions, such as stroke, trauma or neurodegenerative disorders, by facilitating motor and pain control. Such interfaces, chronically implanted in the CNS, need to be biocompatible and have the ability to stimulate and record nerve signals. However, neural devices of today are not fully optimized. Nanostructured surfaces may improve electrical properties and lower evoked tissue responses. Vertical gallium phosphide (GaP) nanowires epitaxially grown from a GaP surface is one way of creating nanostructured electrodes. Thus, we chose to study the soft tissue reactions evoked by GaP surfaces. GaP and the control material titanium (Ti) were implanted in the rat abdominal wall for evaluation of tissue reactions after 1, 6, or 12 weeks. The foreign-body response was evaluated by measuring the reactive capsule thickness and by quantification of ED1-positive macrophages and total cells in the capsule. Furthermore, the concentration of Ga was measured in blood, brain, liver and kidneys. Statistically significant differences were noticed between GaP and Ti at 12 weeks for total and ED1-positive cell densities in the capsule. The chemical analysis showed that the concentration of Ga in brain, liver and kidneys increased during 12 weeks of implantation, indicating loss of Ga from the implant. Taken together, our results show that the biocompatible properties of GaP are worse than those of the well-documented biomaterial Ti.
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| 9. |
- Gustavsson, Per, et al.
(författare)
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Galectin-3 inhibits Schwann cell proliferation in cultured sciatic nerve
- 2007
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Ingår i: NeuroReport. - 1473-558X. ; 18:7, s. 669-673
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Tidskriftsartikel (refereegranskat)abstract
- The production of galectin-3, a carbohydrate-binding mammalian lectin, is upregulated in Schwann cells after peripheral nerve injury in areas where Schwann cells proliferate. Here we tested if galectin-3 affected proliferation of Schwann cells in cultured sciatic nerve segments. Galectin-3 significantly decreased the number of bromodeoxyuridine-labelled Schwann cell nuclei. Neither lactose nor a synthetic inhibitor directed against the carbohydrate-binding region abolished the effects of galectin-3. In addition, a mutant galectin-3 unable to bind endogenous carbohydrates had similar effects as normal galectin-3. We conclude that galectin-3 reduces proliferation of Schwann cells in cultured sciatic nerve segments by a mechanism which is independent of its carbohydrate-binding moiety.
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| 10. |
- Gustavsson, Per, et al.
(författare)
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Neurite guidance on protein micropatterns generated by a piezoelectric microdispenser
- 2007
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Ingår i: Biomaterials. - : Elsevier BV. - 1878-5905 .- 0142-9612. ; 28:6, s. 1141-1151
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we developed a microdispenser technique in order to create protein patterns for guidance of neurites from cultured adult mouse dorsal root ganglia (DRG). The microdispenser is a micromachined silicon device that ejects 100 picolitre droplets and has the ability to position the droplets with a precision of 6-8 mu m. Laminin and bovine serum albumin (BSA) was used to create adhesive and non-adhesive protein lines on polystyrene surfaces (cell culture dishes). Whole-mounted DRGs were then positioned close to the patterns and neurite outgrowth was monitored. The neurites preferred to grow on laminin lines as compared to the unpatterned plastic. When patterns were made from BSA the neurites preferred to grow in between the lines on the unpatterned plastic surface. We conclude that microdispensing can be used for guidance of sensory neurites. The advantages of microdispensing is that it is fast, flexible, allows deposition of different protein concentrations and enables patterning on delicate surfaces due to its non-contact mode of operation. It is conceivable that microdispensing can be utilized for the creation of protein patterns for guiding neurites to obtain in vitro neural networks, in tissue engineering or rapid screening for guiding proteins. (c) 2006 Elsevier Ltd. All rights reserved.
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