1. |
- Nilsson, H-J., et al.
(författare)
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Profound inhibition of chronic itch induced by stimulation of thin cutaneous nerve fibres
- 2004
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Ingår i: Journal of the European Academy of Dermatology and Venereology. - : Elsevier. - 0926-9959 .- 1468-3083. ; 18:1, s. 37-43
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Despite the fact that severe itch is common in many dermatological diseases, the therapeutic arsenal against itching is limited. From neurophysiological experiments, using a new technique termed cutaneous field stimulation, it is known that acute itch can be effectively relieved by stimulation of cutaneous nociceptors. METHODS: We tested the effects of cutaneous field stimulation (25 min, 16 electrodes, 4 Hz per electrode, up to 0.8 mA) on chronic itch due to atopic dermatitis. Transcutaneous electrical nerve stimulation (100 Hz, up to 26 mA) was used for comparison. In 27 patients, itch was measured just prior to, during and at regular intervals up to 12 h after either type of treatment. RESULTS: Both treatments augmented the itch sensation during ongoing stimulation, presumably reflecting an altered sensory processing in the somatosensory pathways of chronic itch patients. However, after cessation of cutaneous field stimulation, but not transcutaneous electrical nerve stimulation, the itch sensation was significantly depressed for up to 7 h. The peak inhibitory effect (about 25% of control) was reached between 1 and 5 h poststimulation. Neither treatment had any significant effect on alloknesis, as measured before and 10 min after stimulation. CONCLUSION: It is concluded that cutaneous field stimulation strongly depresses chronic itch, and is a potentially useful symptomatic treatment of itch.
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3. |
- Andersen, Michael Aagaard, et al.
(författare)
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Polydimethylsiloxane as a more biocompatible alternative to glass in optogenetics
- 2023
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Ingår i: Scientific Reports. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Optogenetics is highly useful to stimulate or inhibit defined neuronal populations and is often used together with electrophysiological recordings. Due to poor penetration of light in tissue, there is a need for biocompatible wave guides. Glass wave guides are relatively stiff and known to cause glia reaction that likely influence the activity in the remaining neurons. We developed highly flexible micro wave guides for optogenetics that can be used in combination with long-lasting electrophysiological recordings. We designed and evaluated polydimethylsiloxane (PDMS) mono-fibers, which use the tissue as cladding, with a diameter of 71 ± 10 µm and 126 ± 5 µm. We showed that micro PDMS fibers transmitted 9–33 mW/mm2 light energy enough to activate channelrhodopsin. This was confirmed in acute extracellular recordings in vivo in which optogenetic stimulation through the PDMS fibers generated action potentials in rat hippocampus with a short onset latency. PDMS fibers had significantly less microglia and astrocytic activation in the zone nearest to the implant as compared to glass. There was no obvious difference in number of adjacent neurons between size matched wave guides. Micro PDMS wave guide demonstrates in vivo functionality and improved biocompatibility as compared to glass. This enables the delivery of light with less tissue damage.
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4. |
- Andoralov, Viktor, et al.
(författare)
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Biofuel cell based on microscale nanostructured electrodes with inductive coupling to rat brain neurons
- 2013
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; :3
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Tidskriftsartikel (refereegranskat)abstract
- Miniature, self-contained biodevices powered by biofuel cells may enable a new generation of implantable, wireless, minimally invasive neural interfaces for neurophysiological in vivo studies and for clinical applications. Here we report on the fabrication of a direct electron transfer based glucose/oxygen enzymatic fuel cell (EFC) from genuinely three-dimensional (3D) nanostructured microscale gold electrodes, modified with suitable biocatalysts. We show that the process underlying the simple fabrication method of 3D nanostructured electrodes is based on an electrochemically driven transformation of physically deposited gold nanoparticles. We experimentally demonstrate that mediator-, cofactor-, and membrane-less EFCs do operate in cerebrospinal fluid and in the brain of a rat, producing amounts of electrical power sufficient to drive a self-contained biodevice, viz. 7 μW cm−2 in vitro and 2 μW cm−2 in vivo at an operating voltage of 0.4 V. Last but not least, we also demonstrate an inductive coupling between 3D nanobioelectrodes and living neurons.
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6. |
- Bakalkin, Georgy, et al.
(författare)
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Unilateral traumatic brain injury of the left and right hemisphere produces the left hindlimb response in rats
- 2021
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Ingår i: Experimental Brain Research. - : Springer Science and Business Media LLC. - 0014-4819 .- 1432-1106. ; 239:7, s. 2221-2232
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury and stroke result in hemiplegia, hemiparesis, and asymmetry in posture. The effects are mostly contralateral; however, ipsilesional deficits may also develop. We here examined whether ablation brain injury and controlled cortical impact (CCI), a rat model of clinical focal traumatic brain injury, both centered over the left or right sensorimotor cortex, induced hindlimb postural asymmetry (HL-PA) with contralesional or ipsilesional limb flexion. The contralesional hindlimb was flexed after left or right side ablation injury. In contrast, both the left and right CCI unexpectedly produced HL-PA with flexion on left side. The flexion persisted after complete spinal cord transection suggesting that CCI triggered neuroplastic processes in lumbar neural circuits enabling asymmetric muscle contraction. Left limb flexion was exhibited under pentobarbital anesthesia. However, under ketamine anesthesia, the body of the left and right CCI rats bent laterally in the coronal plane to the ipsilesional side suggesting that the left and right injury engaged mirror-symmetrical motor pathways. Thus, the effects of the left and right CCI on HL-PA were not mirror-symmetrical in contrast to those of the ablation brain injury, and to the left and right CCI produced body bending. Ipsilateral effects of the left CCI on HL-PA may be mediated by a lateralized motor pathway that is not affected by the left ablation injury. Alternatively, the left-side-specific neurohormonal mechanism that signals from injured brain to spinal cord may be activated by both the left and right CCI but not by ablation injury.
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7. |
- Biro, T, et al.
(författare)
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How best to fight that nasty itch - from new insights into the neuroimmunological, neuroendocrine, and neurophysiological bases of pruritus to novel therapeutic approaches
- 2005
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Ingår i: Experimental Dermatology. - : Wiley. - 0906-6705 .- 1600-0625. ; 14:3, s. 225-225
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Tidskriftsartikel (refereegranskat)abstract
- While the enormous clinical and psychosocial importance of pruritus in many areas of medicine and the detrimental effects of chronic 'itch' on the quality of life of an affected individual are widely appreciated, the complexity of this sensation is still often grossly underestimated. The current Controversies feature highlights this complexity by portraying pruritus as a truly interdisciplinary problem at the crossroads of neurophysiology, neuroimmunology, neuropharmacology, protease research, internal medicine, and dermatology, which is combated most successfully if one keeps the multilayered nature of 'itch' in mind and adopts a holistic treatment approach - beyond the customary, frequently frustrane monotherapy with histamine receptor antagonists. In view of the often unsatisfactory, unidimensional, and altogether rather crude standard instruments for pruritus management that we still tend to use in clinical practice today, an interdisciplinary team of pruritus experts here critically examines recent progress in pruritus research that future itch management must take into consideration. Focusing on new insights into the neuroimmunological, neuroendocrine, and neurophysiological bases of pruritus, and discussing available neuropharmacological tools, specific research avenues are highlighted, whose pursuit promises to lead to novel, and hopefully more effective, forms of pruritus management.
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10. |
- D. Holmkvist, Alexander, et al.
(författare)
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Hydrophobic ion pairing of a minocycline/Ca(2+)/AOT complex for preparation of drug-loaded PLGA nanoparticles with improved sustained release.
- 2016
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 1873-3476 .- 0378-5173. ; 499:1-2, s. 351-357
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Tidskriftsartikel (refereegranskat)abstract
- Polymeric nanoparticles is an established and efficient means to achieve controlled release of drugs. Incorporation of minocycline, an antibiotic with anti-inflammatory and neuroprotective properties, into biodegradable nanoparticles may therefore provide an efficient means to combat foreign body reactions to implanted electrodes in the brain. However, minocycline is commonly associated with poor encapsulation efficiencies and/or fast release rates due to its high solubility in water. Moreover, minocycline is unstable under conditions of low and high pH, heat and exposure to light, which exacerbate the challenges of encapsulation. In this work drug loaded PLGA nanoparticles were prepared by a modified emulsification-solvent-diffusion technique and characterized for size, drug encapsulation and in vitro drug release. A novel hydrophobic ion pair complex of minocycline, Ca(2+) ions and the anionic surfactant AOT was developed to protect minocycline from degradation and prolong its release. The optimized formulation resulted in particle sizes around 220nm with an entrapment efficiency of 43% and showed drug release over 30 days in artificial cerebrospinal fluid. The present results constitute a substantial increase in release time compared to what has hitherto been achieved for minocycline and indicate that such particles might provide useful for sustained drug delivery in the CNS.
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11. |
- Ejserholm, Fredrik, et al.
(författare)
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A polymer based electrode array for recordings in the cerebellum
- 2011
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Ingår i: 2011 5th International IEEE/EMBS Conference on Neural Engineering (NER). - 9781424441402 ; , s. 376-379
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Konferensbidrag (refereegranskat)abstract
- A polymer foil based array with 9 gold electrodes for chronic electrophysiological recordings in the CNS has been developed. A polymer, SU-8, is pattered using photolithography techniques used every day in micro fabrication. This is beneficial if the electrode would be manufactured on a large scale basis. The technique makes it easy to adapt the array to best fit the structure of interest at the time, in this study the rat cerebellar cortex. The use of SU-8 as the base of the array makes the array very flexible, hence lets it stay close to the same cells following the movement of the brain. The electrodes can then be modified with platinum black to lower the impedance of the electrode up to one order of magnitude, making us able to create smaller electrodes but keeping the low impedance necessary to get a get the signal to noise ratio required. Platinum black modified arrays were also implanted chronically and showed excellent signal recording capabilities in rat cerebellum.
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12. |
- Ejserholm, Fredrik, et al.
(författare)
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A polymer neural probe with tunable flexibility
- 2013
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Ingår i: 2013 6th International IEEE/EMBS Conference on Neural Engineering (NER). - 1948-3546. - 9781467319690 ; , s. 691-694
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Konferensbidrag (refereegranskat)abstract
- A novel polymeric material, off stoichiometry thiol-ene-epoxy (OSTE+), has been evaluated for the fabrication of neural implants. OSTE+ is easily photo-structurable and exhibits mechanical properties suitable for stable implantation of the probe into brain tissue, while being sufficiently soft at physiological temperatures to reduce living tissue damage. The facile processing of OSTE+ allows use in applications where SU-8 or polyimide currently are the materials of choice. Uniquely, OSTE+ has a Young’s modulus of 1.9 GPa at 10 °C decreasing almost two orders of magnitude to 30 MPa at 40 °C, which can be compared to the Young’s modulus of 2.1 GPa for SU-8. We show a probe, with nine gold electrode sites, implanted into 0.5% agar at 40 °C using active cooling during the implantation.
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13. |
- Ejserholm, Fredrik, et al.
(författare)
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μ-Foil Polymer Electrode Array for Intracortical Neural Recordings
- 2014
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Ingår i: IEEE Journal of Translational Engineering in Health and Medicine. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- We have developed a multichannel electrode array—termed μ-foil—that comprises ultrathin and flexible electrodes protruding from a thin foil at fixed distances. In addition to allowing some of the active sites to reach less compromised tissue, the barb-like protrusions that also serves the purpose of anchoring the electrode array into the tissue. This paper is an early evaluation of technical aspects and performance of this electrode array in acute in vitro/in vivo experiments. The interface impedance was reduced by up to two decades by electroplating the active sites with platinum black. The platinum black also allowed for a reduced phase lag for higher frequency components. The distance between the protrusions of the electrode array was tailored to match the architecture of the rat cerebral cortex. In vivo acute measurements confirmed a high signal-to-noise ratio for the neural recordings, and no significant crosstalk between recording channels.
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14. |
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15. |
- Ekerot, C F, et al.
(författare)
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The postsynaptic dorsal column pathway mediates cutaneous nociceptive information to cerebellar climbing fibres in the cat
- 1991
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Ingår i: Journal of Physiology. - 1469-7793. ; 441, s. 275-284
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Tidskriftsartikel (refereegranskat)abstract
- 1. The location in the spinal cord of the pathway mediating cutaneous nociceptive C fibre input to climbing fibres projecting to the forelimb area of the C3 zone in the cerebellar anterior lobe was investigated in pentobarbitone-anaesthetized cats. Lesions of the spinal cord at the segmental level of C3 sparing the dorsal funiculi (DF preparation) or lesions of the ipsilateral and part of the contralateral dorsal funiculi were made. 2. In the DF preparation, the cutaneous input to climbing fibres projecting to the C3 zone was the same as in cats with an intact spinal cord. Also, the topography of tactile and nociceptive receptive fields and the distribution of A- and C fibre-evoked climbing fibre field potentials was similar to that in cats with an intact spinal cord. 3. In cats with an initially intact spinal cord the cutaneous nociceptive C fibre input and the topographically well organized tactile input to the C3 climbing fibres disappeared following a lesion of the ipsilateral and part of the contralateral dorsal funiculi. Following this lesion the receptive fields of the climbing fibres became indistinct and only irregular responses were evoked on skin stimulation. 4. It is concluded that the cutaneous nociceptive C fibre input from the forelimb to climbing fibres projecting to the C3 zone is mediated by the ipsilateral dorsal funiculus. Since cutaneous C fibres terminate exclusively in the spinal cord close to their entrance zone the postsynaptic dorsal column pathway must be part of this spino-olivocerebellar pathway.
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16. |
- Ekerot, Carl-Fredrik, et al.
(författare)
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Topography and nociceptive receptive fields of climbing fibres projecting to the cerebellar anterior lobe in the cat
- 1991
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Ingår i: Journal of Physiology. - 1469-7793. ; 441:1, s. 257-274
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Tidskriftsartikel (refereegranskat)abstract
- 1. The cutaneous receptive fields of 225 climbing fibres projecting to the forelimb area of the C3 zone in the cerebellar anterior lobe were mapped in the pentobarbitoneanaesthetized cat. Responses in climbing fibres were recorded as complex spikes in Purkinje cells. 2. A detailed topographical organization of the nociceptive climbing fibre input to the C3 zone was found. In the medial C3 zone climbing fibres with receptive fields covering proximal and/or lateral parts of the forelimb projected most medially. Climbing fibres with receptive fields located more medially on the forelimb projected successively more laterally. The sequence of receptive fields found in the lateral C3 zone was roughly the reverse of that in the medial C3 zone. Climbing fibres with receptive fields restricted to the digits projected preferentially to the caudal part of the forelimb area, whereas those with receptive fields covering both proximal and ventral areas of the forearm projected to more rostral parts. 3. The representation of the forelimb was uneven. Receptive fields with a focus on the digits or along the lateral side of the forearm dominated. 4. The proximal borders of the receptive fields were located close to joints. The area from which maximal responses were evoked was usually located eccentrically within the receptive field. Based on spatial characteristics the receptive fields could be divided into eight classes, which in turn were tentatively divided into subclasses. Similar subclasses of receptive fields were found in different cats. This classification was further supported by the results of a quantitative analysis of eighty-nine climbing fibres. The receptive fields of these climbing fibres were mapped with standardized noxious stimulation. 5. Climbing fibres terminating within sagittal strips (width, 100-300 ,tm; length, > 1 mm) had receptive fields which belonged to the same subclass. There were commonly abrupt changes in receptive fields between such microzones. Most classes of receptive fields were found in both the medial and the lateral parts of the C3 zone. However, receptive fields with a focus on the ventral side of either the metacarpals, the wrist or the forearm were found only in the medial part of the C3 zone. Furthermore, the class of receptive fields restricted to the lateral side of the upper arm and shoulder was only found in the lateral part of the C3 zone. 6. In the discussion, it is proposed that climbing fibres projecting to each microzone carry information from spinal multireceptive reflex arcs acting on a single muscle or a group of synergistic muscles. It is further suggested that each microzone controls the activity of the corresponding motoneurone pool(s) via pathways through the anterior interposed nucleus and the red nucleus.
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17. |
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18. |
- 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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19. |
- 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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20. |
- 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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21. |
- Etemadi, Leila, et al.
(författare)
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Embedded Ultrathin Cluster Electrodes for Long-Term Recordings in Deep Brain Centers
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Neural interfaces which allow long-term recordings in deep brain structures in awake freely moving animals have the potential of becoming highly valuable tools in neuroscience. However, the recording quality usually deteriorates over time, probably at least partly due to tissue reactions caused by injuries during implantation, and subsequently micro-forces due to a lack of mechanical compliance between the tissue and neural interface. To address this challenge, we developed a gelatin embedded neural interface comprising highly flexible electrodes and evaluated its long term recording properties. Bundles of ultrathin parylene C coated platinum electrodes (N = 29) were embedded in a hard gelatin based matrix shaped like a needle, and coated with Kollicoat™ to retard dissolution of gelatin during the implantation. The implantation parameters were established in an in vitro model of the brain (0.5% agarose). Following a craniotomy in the anesthetized rat, the gelatin embedded electrodes were stereotactically inserted to a pre-target position, and after gelatin dissolution the electrodes were further advanced and spread out in the area of the subthalamic nucleus (STN). The performance of the implanted electrodes was evaluated under anesthesia, during 8 weeks. Apart from an increase in the median-noise level during the first 4 weeks, the electrode impedance and signal-to-noise ratio of single-units remained stable throughout the experiment. Histological postmortem analysis confirmed implantation in the area of STN in most animals. In conclusion, by combining novel biocompatible implantation techniques and ultra-flexible electrodes, long-term neuronal recordings from deep brain structures with no significant deterioration of electrode function were achieved.
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22. |
- Forni, Matilde, et al.
(författare)
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3D microelectrode cluster and stimulation paradigm yield powerful analgesia without noticeable adverse effects
- 2021
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:41
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Tidskriftsartikel (refereegranskat)abstract
- The lack of satisfactory treatment for persistent pain profoundly impairs the quality of life for many patients. Stimulation of brainstem pain control systems can trigger powerful analgesia, but their complex network organization frequently prevents separation of analgesia from side effects. To overcome this long-standing challenge, we developed a biocompatible gelatin-embedded cluster of ultrathin microelectrodes that enables fine-tuned, high-definition three-dimensional stimulation in periaqueductal gray/dorsal raphe nucleus in awake rats. Analgesia was assessed from both motor reactions and intracortical signals, corresponding to pain-related signals in humans. We could select an individual-specific subset of microelectrodes in each animal that reliably provided strong pain inhibition during normal and hyperalgesia conditions, without noticeable behavioral side effects. Gait, spontaneous cortical activity at rest, and cortical tactile responses were minimally affected, indicating a highly selective action. In conclusion, our developed biocompatible microelectrode cluster and stimulation paradigm reliably enabled powerful, fine-tuned, and selective analgesia without noticeable side effects.
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23. |
- Forni, Matilde, et al.
(författare)
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Sustained and potent analgesia with negligible side effects enabled by adaptive individualized granular stimulation in rat brainstem
- 2023
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Ingår i: Journal of Neural Engineering. - 1741-2560. ; 20:3
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. To clarify if an adaptive current stimulation protocol, in which current amplitude is modulated during continuous stimulation, provides better efficacy than constant current stimulation protocol with respect to analgesia caused by individualized stimulation in rat periaqueductal gray matter (PAG) /dorsal raphe nuclei (DRN). Approach. Ultrathin microelectrodes adapted for recording (n = 6) and stimulation (n = 16) were implanted in rat primary somatosensory cortex and PAG/DRN, respectively. In each animal included (n = 12), a subset of PAG/DRN microelectrodes (n = 1-3 per animal) was selected that on simultaneous stimulation blocked nociceptive withdrawal reflexes in awake unrestrained animals without noticeable side effects. Analgesic effects were subsequently assessed from both nociceptive withdrawal reflexes and intracortical pain-related responses on CO2 laser hind paw stimulation. The analgesic effects of adaptive current PAG/DRN stimulation comprising incremental increases of 5 μA/microelectrode (initial median current 30 μA/microelectrode) when effects declined were compared to the effects of constant current stimulation. Behavioral effects and brain state related changes were analyzed using quantitative movement analysis and electrocorticography (recorded on top of the dura mater), respectively. Tissue reactions and probe placement in PAG/DRN were assessed with immunohistochemistry. Main results. Powerful and sustained (4 h) analgesia was achieved with the adaptive current protocol within a rather wide area of PAG/DRN. Analgesic after-effects were seen for up to 30 min. Behavioral and brain state related side effects were minimal. Moreover, 6 weeks after implantation, there were no traces of bleedings, only small glial reactions and small but not statistically significant loss of neurons nearby indicating that the microelectrode stimulation employed is biocompatible. Significance. The results indicate that sustained and powerful analgesia with minimal side effects can be achieved by granular and individualized stimulation in PAG/DRN using an adaptive current stimulation protocol. This microelectrode technology and stimulation paradigm thus has the potential of providing a highly efficient and safe pain therapy.
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24. |
- Garwicz, Martin, et al.
(författare)
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Common principles of sensory encoding in spinal reflex modules and cerebellar climbing fibres.
- 2002
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Ingår i: Journal of Physiology. - : Wiley. - 1469-7793 .- 0022-3751. ; 540:Pt 3, s. 1061-1069
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Tidskriftsartikel (refereegranskat)abstract
- An important step towards understanding the function of olivo-cerebellar climbing fibres must be to clarify what they signal. We suggest that climbing fibres projecting to paravermal cerebellum mediate highly integrated sensorimotor information derived from activity in spinal withdrawal reflex modules acting on single forelimb muscles. To test this hypothesis, cutaneous nociceptive receptive fields of spinal reflex modules were mapped and compared to those of climbing fibres. Quantitative methods were used both for mapping and for comparing receptive fields. The organization of muscle afferent input converging on individual climbing fibres was analysed in the light of results from receptive field comparisons. Individual cutaneous receptive fields in the two systems were readily matched. Matched pairs were highly similar with regard to detailed distributions of sensitivity: correlation coefficient r = 0.85; overlap of receptive field foci 72 % (average values). The olivary targets of muscle afferents from a given muscle were mainly climbing fibres with cutaneous receptive fields similar to that of the muscle itself, but to a lesser extent also other climbing fibres. In conclusion, paravermal climbing fibres apparently convey information integrating (i) cutaneous input to an individual spinal withdrawal reflex module, (ii) muscle afferent input from the output muscle of that module and (iii) muscle afferent input from muscles that constitute the output of functionally related modules. This suggests that an individual climbing fibre signals cutaneous sensory events reflecting activity of a single muscle conditional upon the functional state of the muscle itself and that of functionally related muscles.
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25. |
- Garwicz, Martin, et al.
(författare)
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Distribution of Cutaneous Nociceptive and Tactile Climbing Fibre Input to Sagittal Zones in Cat Cerebellar Anterior Lobe
- 1992
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 4:4, s. 289-295
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Tidskriftsartikel (refereegranskat)abstract
- Climbing fibres projecting to the cerebellar C3 zone (and the related C1 and Y zones) receive spatially well organized tactile and nociceptive inputs from the skin. In the present study, cutaneous tactile and nociceptive input to climbing fibres projecting to the X, B, C2 and D1 zones in lobule V were investigated in pentobarbitone-anaesthetized cats. From the present results and previous studies, it is concluded that the X, C1, CX, C3 and Y zones receive cutaneous nociceptive climbing fibre input. By contrast, climbing fibres to the B, C2 and D1 zones lack cutaneous nociceptive input. Tactile input was found in all zones. The spatial organization of receptive fields of climbing fibres projecting to the X and D1 zones was similar to that in the C3 zone. They were located on the ipsilateral forelimb, mainly its lateral and distal parts, and their proximal borders were located close to joints. In the B zone, more than half of the receptive fields of climbing fibres were confined to the ipsilateral hind- or forelimb. However, frequently more than one limb and parts of the trunk were included. In the C2 zone, the majority of climbing fibres had distal ipsi- or bilateral receptive fields on the forelimbs, often also including the head/face. Some of the bilateral forelimb receptive fields additionally included the hindlimbs ipsi- or bilaterally. The results indicate that each zone has a characteristic set of climbing fibre receptive fields, which is probably related to its efferent control functions.
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