1. |
- Augestad, Ingrid Lovise, et al.
(författare)
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Effects of Neural Stem Cell and Olfactory Ensheathing Cell Co-transplants on Tissue Remodelling After Transient Focal Cerebral Ischemia in the Adult Rat
- 2017
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Ingår i: Neurochemical Research. - : SPRINGER/PLENUM PUBLISHERS. - 0364-3190 .- 1573-6903. ; 42:6, s. 1599-1609
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Tidskriftsartikel (refereegranskat)abstract
- Effective transplant-mediated repair of ischemic brain lesions entails extensive tissue remodeling, especially in the ischemic core. Neural stem cells (NSCs) are promising reparative candidates for stroke induced lesions, however, their survival and integration with the host-tissue post-transplantation is poor. In this study, we address this challenge by testing whether co-grafting of NSCs with olfactory ensheathing cells (OECs), a special type of glia with proven neuroprotective, immunomodulatory, and angiogenic effects, can promote graft survival and host tissue remodelling. Transient focal cerebral ischemia was induced in adult rats by a 60-min middle cerebral artery occlusion (MCAo) followed by reperfusion. Ischemic lesions were verified by neurological testing and magnetic resonance imaging. Transplantation into the globus pallidus of NSCs alone or in combination with OECs was performed at two weeks post-MCAo, followed by histological analyses at three weeks post-transplantation. We found evidence of extensive vascular remodelling in the ischemic core as well as evidence of NSC motility away from the graft and into the infarct border in severely lesioned animals co-grafted with OECs. These findings support a possible role of OECs as part of an in situ tissue engineering paradigm for transplant mediated repair of ischemic brain lesions.
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2. |
- Bandyopadhyay, Sulalit, et al.
(författare)
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Growing gold nanostructures for shape-selective cellular uptake
- 2018
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Ingår i: Nanoscale Research Letters. - : SpringerOpen. - 1931-7573 .- 1556-276X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- With development in the synthesis of shape- and size-dependent gold (Au) nanostructures (NSs) and their applications in nanomedicine, one of the biggest challenges is to understand the interaction of these shapes with cancer cells. Herein, we study the interaction of Au NSs of five different shapes with glioblastoma-astrocytoma cells. Three different shapes (nanorods, tetrahexahedra, and bipyramids), possessing tunable optical properties, have been synthesized by a single-step seed-mediated growth approach employing binary surfactant mixtures of CTAB and a secondary surfactant By the use of two-step seed-mediated approach, we obtained new NSs, named nanomakura (Makura is a Japanese word used for pillow) which is reported for the first time here. Spherical Au nanoparticles were prepared by the Turkevich method. To study NS-cell interactions, we functionalized the NSs using thiolated PEG followed by 11-Mercaptoundecanoic acid. The influence of shape and concentration of NSs on the cytotoxicity were assessed with a LIVE/DEAD assay in glioblastoma-astrocytoma cells. Furthermore, the time-dependent uptake of nanomakura was studied with TEM. Our results indicate that unlike the other shapes studied here, the nanomakura were taken up both via receptor-mediated endocytosis and macropinocytosis. Thus, from our library of different NSs with similar surface functionality, the shape is found to be an important parameter for cellular uptake.
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3. |
- McDonagh, Birgitte H, et al.
(författare)
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Controlling the self-assembly and optical properties of gold nanoclusters and gold nanoparticles biomineralized with bovine serum albumin
- 2015
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Ingår i: RSC Advances. - : Royal Society of Chemistry. - 2046-2069. ; 5:122, s. 101101-101109
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Tidskriftsartikel (refereegranskat)abstract
- While the size-dependent optical properties of BSA-stabilized gold nanoclusters are well known, the timedependent growth mechanism remains to be described. Herein, we systematically compare two synthesis methods with and without ascorbic acid, and show that tuning of BSA-stabilized gold nanoclusters (AuNCs) of different sizes can be performed without the aid of an extrinsic reducing agent and with good reproducibility. We also show that adding ascorbic acid yields larger BSA-stabilized gold nanoparticles (AuNPs), and that AuNPs can only form above a threshold gold precursor concentration. Using computed tomography, we describe how these biomineralized AuNPs show size-dependent X-ray attenuation. Growth of BSA-stabilized AuNCs and AuNPs, over a range of gold precursor concentrations, was followed with steady-state fluorescence and UV-vis spectroscopy for one week, constituting the first study of its kind. Based on our results, we propose a mechanism for BSA-stabilization of AuNCs and AuNPs that can further aid in selective growth of discrete AuNCs and AuNPs.
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4. |
- McDonagh, Birgitte Hjelmeland, et al.
(författare)
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L-DOPA-Coated Manganese Oxide Nanoparticles as Dual MRI Contrast Agents and Drug-Delivery Vehicles
- 2016
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Ingår i: Small. - : Wiley. - 1613-6810 .- 1613-6829. ; 12:3, s. 301-306
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Tidskriftsartikel (refereegranskat)abstract
- Manganese oxide nanoparticles (MONPs) are capable of time-dependent magnetic resonance imaging contrast switching as well as releasing a surface-bound drug. MONPs give T2/T2* contrast, but dissolve and release T1-active Mn2+ and l-3,4-dihydroxyphenylalanine. Complementary images are acquired with a single contrast agent, and applications toward Parkinson's disease are suggested.
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5. |
- McDonagh, Birgitte H., et al.
(författare)
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Self-assembly and characterization of transferrin-gold nanoconstructs and their interaction with bio-interfaces
- 2015
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Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 7:17, s. 8062-8070
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Tidskriftsartikel (refereegranskat)abstract
- Transferrin (Tf) conjugated to gold nanoparticles and clusters combine the protein's site-specific receptor targeting capabilities with the optical properties imparted by the nano-sized gold. We have described two different synthesis protocols, one yielding fluorescent Tf-stabilized gold nanoclusters (AuNCs) and one yielding Tf-stabilized gold nanoparticles that exhibit localized surface plasmon resonance. We demonstrate that the synthetic route employed has a large influence both on the gold nanostructure formed, and also on the structural integrity of the protein. A slight protein unfolding allows stronger interaction with lipids, and was found to significantly perturb lipid monolayers. Interactions between the protein-gold nanostructures and three different cell types were also assessed, indicating that the enhanced membrane affinity may be attributed to intercellular membrane differences.
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6. |
- Podobinska, Martyna, et al.
(författare)
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Epigenetic Modulation of Stem Cells in Neurodevelopment : The Role of Methylation and Acetylation
- 2017
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Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media S.A.. - 1662-5102. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- The coordinated development of the nervous system requires fidelity in the expression of specific genes determining the different neural cell phenotypes. Stem cell fate decisions during neurodevelopment are strictly correlated with their epigenetic status. The epigenetic regulatory processes, such as DNA methylation and histone modifications discussed in this review article, may impact both neural stem cell (NSC) self-renewal and differentiation and thus play an important role in neurodevelopment. At the same time, stem cell decisions regarding fate commitment and differentiation are highly dependent on the temporospatial expression of specific genes contingent on the developmental stage of the nervous system. An interplay between the above, as well as basic cell processes, such as transcription regulation, DNA replication, cell cycle regulation and DNA repair therefore determine the accuracy and function of neuronal connections. This may significantly impact embryonic health and development as well as cognitive processes such as neuroplasticity and memory formation later in the adult.
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7. |
- Sandvig, Axel, et al.
(författare)
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Connectomics of morphogenetically engineered neurons as a predictor of functional integration in the ischemic brain
- 2019
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Ingår i: Frontiers in Neurology. - : Frontiers Media S.A.. - 1664-2295. ; 10
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Forskningsöversikt (refereegranskat)abstract
- Recent advances in cell reprogramming technologies enable the in vitro generation of theoretically unlimited numbers of cells, including cells of neural lineage and specific neuronal subtypes from human, including patient-specific, somatic cells. Similarly, as demonstrated in recent animal studies, by applying morphogenetic neuroengineering principles in situ, it is possible to reprogram resident brain cells to the desired phenotype. These developments open new exciting possibilities for cell replacement therapy in stroke, albeit not without caveats. Main challenges include the successful integration of engineered cells in the ischemic brain to promote functional restoration as well as the fact that the underlying mechanisms of action are not fully understood. In this review, we aim to provide new insights to the above in the context of connectomics of morphogenetically engineered neural networks. Specifically, we discuss the relevance of combining advanced interdisciplinary approaches to: validate the functionality of engineered neurons by studying their self-organizing behavior into neural networks as well as responses to stroke-related pathology in vitro; derive structural and functional connectomes from these networks in healthy and perturbed conditions; and identify and extract key elements regulating neural network dynamics, which might predict the behavior of grafted engineered neurons post-transplantation in the stroke-injured brain.
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8. |
- Sandvig, Ioanna, et al.
(författare)
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Neuroplasticity in stroke recovery : The role of microglia in engaging and modifying synapses and networks
- 2018
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Ingår i: European Journal of Neuroscience. - : John Wiley & Sons. - 0953-816X .- 1460-9568. ; 47:12, s. 1414-1428
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Tidskriftsartikel (refereegranskat)abstract
- Neuroplasticity after ischaemic injury involves both spontaneous rewiring of neural networks and circuits as well as functional responses in neurogenic niches. These events involve complex interactions with activated microglia, which evolve in a dynamic manner over time. Although the exact mechanisms underlying these interactions remain poorly understood, increasing experimental evidence suggests a determining role of pro- and anti-inflammatory microglial activation profiles in shaping both synaptogenesis and neurogenesis. While the inflammatory response of microglia was thought to be detrimental, a more complex profile of the role of microglia in tissue remodelling is emerging. Experimental evidence suggests that microglia in response to injury can rapidly modify neuronal activity and modulate synaptic function, as well as be beneficial for the proliferation and integration of neural progenitor cells (NPCs) from endogenous neurogenic niches into functional networks thereby supporting stroke recovery. The manner in which microglia contribute towards sculpting neural synapses and networks, both in terms of activity-dependent and homeostatic plasticity, suggests that microglia-mediated pro- and/or anti-inflammatory activity may significantly contribute towards spontaneous neuronal plasticity after ischaemic lesions. In this review, we first introduce some of the key cellular and molecular mechanisms underlying neuroplasticity in stroke and then proceed to discuss the crosstalk between microglia and endogenous neuroplasticity in response to brain ischaemia with special focus on the engagement of synapses and neural networks and their implications for grey matter integrity and function in stroke repair.
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9. |
- Sandvig, Ioanna, et al.
(författare)
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RGD-peptide modified alginate by a chemoenzymatic strategy for tissue engineering applications
- 2015
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Ingår i: Journal of Biomedical Materials Research. Part A. - : Wiley. - 1549-3296 .- 1552-4965. ; 103:3, s. 896-906
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Tidskriftsartikel (refereegranskat)abstract
- One of the main challenges in tissue engineering and regenerative medicine is the ability to maintain optimal cell function and survival post-transplantation. Biomaterials such as alginates are commonly used for immunoisolation, while they may also provide structural support to the cell transplants by mimicking the extracellular matrix. In this study, arginine-glycine-aspartate (RGD)-peptide-coupled alginates of tailored composition were produced by adopting a unique chemoenzymatic strategy for substituting the nongelling mannuronic acid on the alginate. Alginates with and without RGD were produced with high and low content of G. Using carbodiimide chemistry 0.1-0.2% of the sugar units were substituted by peptide. Furthermore, the characterization by H-1-nuclear magnetic resonance (NMR) revealed by-products from the coupling reaction that partly could be removed by coal filtration. Olfactory ensheathing cells (OECs) and myoblasts were grown in two-dimensional (2D) and 3D cultures of RGD-peptide modified or unmodified alginates obtained by the chemoenzymatically strategy and compared to native alginate. Both OECs and myoblasts adhered to the RGD-peptide modified alginates in 2D cultures, forming bipolar protrusions. OEC encapsulation resulted in cell survival for up to 9 days, thus demonstrating the potential for short-term 3D culture. Myoblasts showed long-term survival in 3D cultures, that is, up to 41 days post encapsulation. The RGD modifications did not result in marked changes in cell viability in 3D cultures. We demonstrate herein a unique technique for tailoring peptide substituted alginates with a precise and flexible composition, conserving the gel forming properties relevant for the use of alginate in tissue engineering. (c) 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 896-906, 2015.
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10. |
- Sandvig, Ioanna, et al.
(författare)
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Strategies to Enhance Implantation and Survival of Stem Cells After Their Injection in Ischemic Neural Tissue
- 2017
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Ingår i: Stem Cells and Development. - : Mary Ann Liebert. - 1547-3287 .- 1557-8534. ; 26:8, s. 554-565
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Tidskriftsartikel (refereegranskat)abstract
- High post-transplantation cell mortality is the main limitation of various approaches that are aimed at improving regeneration of injured neural tissue by an injection of neural stem cells (NSCs) and mesenchymal stromal cells (MStroCs) in and/or around the lesion. Therefore, it is of paramount importance to identify efficient ways to increase cell transplant viability. We have previously proposed the "evolutionary stem cell paradigm," which explains the association between stem cell anaerobic/microaerophilic metabolic set-up and stem cell self-renewal and inhibition of differentiation. Applying these principles, we have identified the main critical point in the collection and preparation of these cells for experimental therapy: exposure of the cells to atmospheric O2, that is, to oxygen concentrations that are several times higher than the physiologically relevant ones. In this way, the primitive anaerobic cells become either inactivated or adapted, through commitment and differentiation, to highly aerobic conditions (20%-21% O2 in atmospheric air). This inadvertently compromises the cells' survival once they are transplanted into normal tissue, especially in the hypoxic/anoxic/ischemic environment, which is typical of central nervous system (CNS) lesions. In addition to the findings suggesting that stem cells can shift to glycolysis and can proliferate in anoxia, recent studies also propose that stem cells may be able to proliferate in completely anaerobic or ischemic conditions by relying on anaerobic mitochondrial respiration. In this systematic review, we propose strategies to enhance the survival of NSCs and MStroCs that are implanted in hypoxic/ischemic neural tissue by harnessing their anaerobic nature and maintaining as well as enhancing their anaerobic properties via appropriate ex vivo conditioning.
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11. |
- Singh, Gurvinder, et al.
(författare)
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Synthesis of gadolinium oxide nanodisks and gadolinium doped iron oxide nanoparticles for MR contrast agents
- 2017
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Ingår i: Journal of materials chemistry. B. - : Royal Society of Chemistry (RSC). - 2050-750X .- 2050-7518. ; 5:3, s. 418-422
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Tidskriftsartikel (refereegranskat)abstract
- Herein, we report the synthesis of differently sized gadolinium oxide nanodisks and gadolinium doped iron oxide spherical and cubic nanoparticles through the thermal decomposition of an oleate precursor. We also demonstrate that these nanoparticles are promising candidates for MR contrast agents.
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12. |
- Tukmachev, Dmitry, et al.
(författare)
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Injectable Extracellular Matrix Hydrogels as Scaffolds for Spinal Cord Injury Repair
- 2016
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Ingår i: Tissue Engineering. Part A. - : Mary Ann Liebert Inc. - 1937-3341 .- 1937-335X. ; 22:3-4, s. 306-317
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Tidskriftsartikel (refereegranskat)abstract
- Restoration of lost neuronal function after spinal cord injury (SCI) still remains a big challenge for current medicine. One important repair strategy is bridging the SCI lesion with a supportive and stimulatory milieu that would enable axonal rewiring. Injectable extracellular matrix (ECM)-derived hydrogels have been recently reported to have neurotrophic potential in vitro. In this study, we evaluated the presumed neuroregenerative properties of ECM hydrogels in vivo in the acute model of SCI. ECM hydrogels were prepared by decellularization of porcine spinal cord (SC) or porcine urinary bladder (UB), and injected into a spinal cord hemisection cavity. Histological analysis and real-time qPCR were performed at 2, 4, and 8 weeks postinjection. Both types of hydrogels integrated into the lesion and stimulated neovascularization and axonal ingrowth into the lesion. On the other hand, massive infiltration of macrophages into the lesion and rapid hydrogel degradation did not prevent cyst formation, which progressively developed over 8 weeks. No significant differences were found between SC-ECM and UB-ECM. Gene expression analysis revealed significant downregulation of genes related to immune response and inflammation in both hydrogel types at 2 weeks post SCI. A combination of human mesenchymal stem cells with SC-ECM did not further promote ingrowth of axons and blood vessels into the lesion, when compared with the SC-ECM hydrogel alone. In conclusion, both ECM hydrogels bridged the lesion cavity, modulated the innate immune response, and provided the benefit of a stimulatory substrate for in vivo neural tissue regeneration. However, fast hydrogel degradation might be a limiting factor for the use of native ECM hydrogels in the treatment of acute SCI.
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13. |
- Valderhaug, Vibeke Devold, et al.
(författare)
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Formation of neural networks with structural and functional features consistent with small-world network topology on surface-grafted polymer particles
- 2019
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Ingår i: Royal Society Open Science. - : Royal Society Publishing. - 2054-5703. ; 6:10
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Tidskriftsartikel (refereegranskat)abstract
- In vitro electrophysiological investigation of neural activity at a network level holds tremendous potential for elucidating underlying features of brain function (and dysfunction). In standard neural network modelling systems, however, the fundamental three-dimensional (3D) character of the brain is a largely disregarded feature. This widely applied neuroscientific strategy affects several aspects of the structure-function relationships of the resulting networks, altering network connectivity and topology, ultimately reducing the translatability of the results obtained. As these model systems increase in popularity, it becomes imperative that they capture, as accurately as possible, fundamental features of neural networks in the brain, such as small-worldness. In this report, we combine in vitro neural cell culture with a biologically compatible scaffolding substrate, surface-grafted polymer particles (PPs), to develop neural networks with 3D topology. Furthermore, we investigate their electrophysiological network activity through the use of 3D multielectrode arrays. The resulting neural network activity shows emergent behaviour consistent with maturing neural networks capable of performing computations, i.e. activity patterns suggestive of both information segregation (desynchronized single spikes and local bursts) and information integration (network spikes). Importantly, we demonstrate that the resulting PP-structured neural networks show both structural and functional features consistent with small-world network topology.
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14. |
- van de Wijdeven, Rosanne, et al.
(författare)
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A novel lab-on-chip platform enabling axotomy and neuromodulation in a multi-nodal network
- 2019
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Ingår i: Biosensors & bioelectronics. - : Elsevier. - 0956-5663 .- 1873-4235. ; 140
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Tidskriftsartikel (refereegranskat)abstract
- Lab-on-chip platforms, such as microfluidic chips and micro-electrode arrays (MEAs) are powerful tools that allow us to manipulate and study neurons in vitro. Microfluidic chips provide a controlled extracellular environment that structures neural networks and facilitates isolation and manipulation at a sub-cellular level. Furthermore, MEAs enable measurement of extracellular electrophysiological activity from single neurons to entire networks. Here, we demonstrate the design, fabrication and application of a 3-nodal microfluidic chip integrated with MEAs as a versatile study platform for neurobiology and pathophysiology. In this work, we evaluate the use of the microfluidic chip to structure a neural network into three separate nodes, interconnected through tunnels that isolate and guide axons into a channel, thus facilitating synaptic contacts between neurons originating from opposite nodes. Furthermore, we demonstrate the utility of the MEA for monitoring developing activity and intra-/inter nodal connectivity of the structured neural network. Finally, we demonstrate the versatility of the platform in two separate experiments. First, we demonstrate the ability to measure intra- and inter-nodal dynamic responses to a fluidically isolated chemical stimulation. Then, we demonstrate the feature of the microfluidic chip enabling the disruption of functional connectivity between nodes and examination of the immediate activity response of the neural network. The platform enables in vitro modelling of neural networks to study their functional connectomes in the context of neurodegenerative disease and CNS trauma, including spinal cord injury.
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15. |
- van de Wijdeven, Rosanne, et al.
(författare)
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Structuring a multi-nodal neural network in vitro within a novel design microfluidic chip
- 2018
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Ingår i: Biomedical microdevices (Print). - : Springer. - 1387-2176 .- 1572-8781. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Neural network formation is a complex process involving axon outgrowth and guidance. Axon guidance is facilitated by structural and molecular cues from the surrounding microenvironment. Micro-fabrication techniques can be employed to produce microfluidic chips with a highly controlled microenvironment for neural cells enabling longitudinal studies of complex processes associated with network formation. In this work, we demonstrate a novel open microfluidic chip design that encompasses a freely variable number of nodes interconnected by axon-permissible tunnels, enabling structuring of multi-nodal neural networks in vitro. The chip employs a partially open design to allow high level of control and reproducibility of cell seeding, while reducing shear stress on the cells. We show that by culturing dorsal root ganglion cells (DRGs) in our microfluidic chip, we were able to structure a neural network in vitro. These neurons were compartmentalized within six nodes interconnected through axon growth tunnels. Furthermore, we demonstrate the additional benefit of open top design by establishing a 3D neural culture in matrigel and a neuronal aggregate 3D culture within the chips. In conclusion, our results demonstrate a novel microfluidic chip design applicable to structuring complex neural networks in vitro, thus providing a versatile, highly relevant platform for the study of neural network dynamics applicable to developmental and regenerative neuroscience.
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16. |
- Augustian, Midhumol, et al.
(författare)
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EEG Analysis from Motor Imagery to Control a Forestry Crane
- 2018
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Ingår i: Intelligent Human Systems Integration (IHSI 2018). - Cham : Springer. - 9783319738871 - 9783319738888 ; , s. 281-286
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Konferensbidrag (refereegranskat)abstract
- Brain-computer interface (BCI) systems can provide people with ability to communicate and control real world systems using neural activities. Therefore, it makes sense to develop an assistive framework for command and control of a future robotic system which can assist the human robot collaboration. In this paper, we have employed electroencephalographic (EEG) signals recorded by electrodes placed over the scalp. The human-hand movement based motor imagery mentalization is used to collect brain signals over the motor cortex area. The collected µ-wave (8–13 Hz) EEG signals were analyzed with event-related desynchronization/synchronization (ERD/ERS) quantification to extract a threshold between hand grip and release movement and this information can be used to control forestry crane grasping and release functionality. The experiment was performed with four healthy persons to demonstrate the proof-of concept BCI system. From this study, it is demonstrated that the proposed method has potential to assist the manual operation of crane operators performing advanced task with heavy cognitive work load.
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17. |
- Sandvig, Axel, et al.
(författare)
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Analysis of Codman microcerebrospinal fluid shunt
- 2018
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Ingår i: Brain and Behavior. - : John Wiley & Sons. - 2162-3279. ; 8:10
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Ventriculo-peritoneal cerebrospinal fluid (CSF) shunt is the most common method of treating pediatric hydrocephalus. The Codman microadjustable valve (CMAV) is a CSF shunt constructed for children. The objective of the study was (a) to analyze complications after insertion of a CMAV shunt in hydrocephalic children, (b)to analyze complications after replacing a CMAV by an adult-type Codman Hakim adjustable valve shunt (CHAV), and to (c) analyze the in vitro characteristics of the CMAV shunt and correlate the findings with the clinical performance of the shunt.Methods: A retrospective study analyzed a cohort of hydrocephalic children who had received a CMAV shunt and later replaced by a CHAV shunt. We report on the complications that resulted from replacing the CMAV with the CHAV. We tested six CMAV shunts with or without an antisiphon device (ASD) in which opening pressure, resistance, sensitivity to abdominal pressure, ASD position dependency, and function were determined. The test results were correlated with the clinical performance of the shunt in the retrospective study.Results: Thirty-seven children (19 boys, 18 girls) were identified. Within the first month after shunt placement, a total of 10 patients (27%) developed complications including infections, hygromas, and shunt dysfunction. Shunt survival varied from 1week to 145 months. Over the 10-year follow-up period, 13 children had their shunts replaced, six of them with a CHAV without any further complications. A bench test of the CMAV was done to test whether the opening pressure was in agreement with the manufacturer's specifications. Our results were generally in agreement with specifications stated by the manufacturer.Conclusion: Replacing a CMAV with a CHAV was well tolerated by the patients. Bench test results were generally in agreement with manufacturers specifications. Replacing a CMAV with a CHAV in pediatric hydrocephalus patients can be accomplished safely.
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18. |
- Sandvig, Axel, et al.
(författare)
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Spontaneous chronic epidural hematoma in the lumbar spine associated with Warfarin intake : a case report
- 2016
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Ingår i: SpringerPlus. - : Springer Science and Business Media LLC. - 2193-1801. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Spontaneous spinal epidural hematomas are rare. However, in patients on anticoagulant treatment the risk may increase. Symptomatically patients may present with radiculopathy and even progressive neurological deficits. Case description: We present a case of a warfarin treated patient with left L5 radiculopathy. MRI was evaluated as showing a lumbar disc prolapse or synovial cyst at L4-L5 level. The patient was operated and an organized material was removed and analysed as a hematoma. No prolapsed disc or synovial cyst was found. The patient was neurologically restored following the operation. Discussion and Evaluation: This case illustrates how spontaneous epidural spinal hematomas can present with symptoms of radiculopathy and radiologically be misinterpreted as a protruding disc or cyst. Conclusion: Warfarin treated patients may have an increased risk of spontaneous spinal epidural hematomas.
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19. |
- Åslund, Andreas K. O., et al.
(författare)
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Nanoparticle delivery to the brain - By focused ultrasound and self-assembled nanoparticle-stabilized microbubbles
- 2015
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 220, s. 287-294
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Tidskriftsartikel (refereegranskat)abstract
- The blood-brain barrier (BBB) constitutes a significant obstacle for the delivery of drugs into the central nervous system(CNS). Nanoparticles have been able to partly overcome this obstacle and can thus improve drug delivery across the BBB. Furthermore, focused ultrasound in combination with gas filled microbubbles has opened the BBB in a temporospatial manner in animal models, thus facilitating drug delivery across the BBB. In the current study we combine these two approaches in our quest to develop a novel, generic method for drug delivery across the BBB and into the CNS. Nanoparticles were synthesized using the polymer poly(butyl cyanoacrylate) (PBCA), and such nanoparticles have been reported to cross the BBB to some extent. Together with proteins, these nanoparticles self-assemble into microbubbles. Using these novel microbubbles in combination with focused ultrasound, we successfully and safely opened the BBB transiently in healthy rats. Furthermore, we also demonstrated that the nanoparticles could cross the BBB and deliver a model drug into the CNS.
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