| 1. |
- Gällentoft, Lina, et al.
(författare)
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Impact of degradable nanowires on long-term brain tissue responses
- 2016
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Ingår i: Journal of Nanobiotechnology. - : Springer Science and Business Media LLC. - 1477-3155. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: A promising approach to improve the performance of neural implants consists of adding nanomaterials, such as nanowires, to the surface of the implant. Nanostructured interfaces could improve the integration and communication stability, partly through the reduction of the cell-to-electrode distance. However, the safety issues of implanted nanowires in the brain need to be evaluated and understood before nanowires can be used on the surface of implants for long periods of time. To this end we here investigate whether implanted degradable nanowires offer any advantage over non-degradable nanowires in a long-term in vivo study (1 year) with respect to brain tissue responses. Results: The tissue response after injection of degradable silicon oxide (SiOx)-coated gallium phosphide nanowires and biostable hafnium oxide-coated GaP nanowires into the rat striatum was compared. One year after nanowire injection, no significant difference in microglial or astrocytic response, as measured by staining for ED1 and glial fibrillary acidic protein, respectively, or in neuronal density, as measured by staining for NeuN, was found between degradable and biostable nanowires. Of the cells investigated, only microglia cells had engulfed the nanowires. The SiOx-coated nanowire residues were primarily seen in aggregated hypertrophic ED1-positive cells, possibly microglial cells that have fused to create multinucleated giant cells. Occasionally, degradable nanowires with an apparently intact shape were found inside single, small ED1-positive cells. The biostable nanowires were found intact in microglia cells of both phenotypes described. Conclusion: The present study shows that the degradable nanowires remain at least partly in the brain over long time periods, i.e. 1 year; however, no obvious bio-safety issues for this degradable nanomaterial could be detected.
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| 2. |
- Mohammed, Mohsin, et al.
(författare)
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Ice coating –A new method of brain device insertion to mitigate acute injuries
- 2020
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Ingår i: Journal of Neuroscience Methods. - : Elsevier BV. - 0165-0270. ; 343
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Tidskriftsartikel (refereegranskat)abstract
- Background: Reduction of insertion injury is likely important to approach physiological conditions in the vicinity of implanted devices intended to interface with the surrounding brain. New methods: We have developed a novel, low-friction coating around frozen, gelatin embedded needles. By introducing a layer of thawing ice onto the gelatin, decreasing surface friction, we mitigate damage caused by the implantation. Results and comparison with existing methods: The acute effects of a transient stab on neuronal density and glial reactions were assessed 1 and 7 days post stab in rat cortex and striatum both within and outside the insertion track using immunohistochemical staining. The addition of a coat of melting ice to the frozen gelatin embedded needles reduced the insertion force with around 50 %, substantially reduced the loss neurons (i.e. reduced neuronal void), and yielded near normal levels of astrocytes within the insertion track 1 day after insertion, as compared to gelatin coated probes of the same temperature without ice coating. There were negligible effects on glial reactions and neuronal density immediately outside the insertion track of both ice coated and cold gelatin embedded needles. This new method of implantation presents a considerable improvement compared to existing modes of device insertion. Conclusions: Acute brain injuries following insertion of e.g. ultra-flexible electrodes, can be reduced by providing an outer coat of ultra-slippery thawing ice. No adverse effect of lowered implant temperature was found, opening the possibility of locking fragile electrode construct configurations in frozen gelatin, prior to implantation into the brain.
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| 3. |
- 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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| 4. |
- Etemadi, Leila, et al.
(författare)
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UVB irradiation induces contralateral changes in galanin, substance P and c-fos immunoreactivity in rat dorsal root ganglia, dorsal horn and lateral spinal nucleus
- 2021
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781. ; 136
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Tidskriftsartikel (refereegranskat)abstract
- The selection of control group is crucial, as the use of an inadequate group may strongly affect the results. In this study we examine the effect on contralateral tissue protein levels, in a model of unilateral UVB irradiation, as the contralateral side is commonly used as a control. Previous studies have shown that UVB irradiation increases immunoreactivity for inflammatory regulated neuropeptides. Unilateral UVB irradiation of rat hind paw was performed and corresponding contralateral spinal cord and dorsal root ganglia (DRG) were collected 2–96 h after and investigated for changes in galanin, substance P and c-fos immunoreactivity. Control tissue was collected from naïve rats. Measurement of skin blood flow from contralateral heel hind paws (Doppler), revealed no change compared to naïve rats. However, UVB irradiation caused a significant reduction in the contralateral proportion of galanin immunopositive DRG neurons, at all-time points, as well as an increase in the contralateral spinal cord dorsal horn, around the central canal and in the lateral spinal nucleus (2–48 h). The contralateral proportion of SP positive DRG neurons and dorsal horn immunoreactivity was unchanged, whereas the lateral spinal nucleus area showed increased immunoreactivity (48 h). UVB irradiation also induced a slight contralateral upregulation of c-fos in the dorsal horn/central canal area (24 and 48 h). In summary, unilateral UVB irradiation induced contralateral changes in inflammatory/nociceptive neuropeptides in spinal cord and afferent pathways involved in pain signaling already within 24 h, a time point when also ipsilateral neurochemical/physiological changes have been reported for rats and humans.
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| 5. |
- Etemadi, Leila, et al.
(författare)
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UVB irradiation induces rapid changes in galanin, substance P and c-fos immunoreactivity in rat dorsal root ganglia and spinal cord
- 2017
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781. ; 87, s. 71-83
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have shown that UVB irradiation induces primary and secondary hyperalgesia in rats and humans peaking about 24 h after UVB exposure. In the present study we investigated the changes in galanin, substance P and c-fos immunoreactivity in rat DRG and spinal cord at the L5 level 2–96 h after UVB irradiation. UVB irradiation of the heel area in rats almost increased the skin blood flow two-fold 24 h after irradiation as measured by laser Doppler technique. UVB irradiation induced a significant reduction of the proportion of galanin positive DRG neurons for all time points, except at 12 h. In the spinal cord, UVB irradiation induced increased immunoreactivity for galanin in the dorsal horn, the area around the central canal and interestingly also in the lateral spinal nucleus 12–96 h after exposure. For substance P the proportion of substance P positive neurons was unchanged but UVB irradiation induced increased substance P immunoreactivity in the dorsal part of the spinal cord 48 h after irradiation. UVB irradiation also induced c-fos immunoreactivity in the dorsal horn and the area around the central canal 24 and 48 h after exposure. This translational model of UVB irradiation will induce rapid changes of neuropeptides implicated in nociceptive signaling in areas known to be of importance for nociception in a time frame, about 24 h after exposure, where also neurophysiological alteration have been described in humans and rats.
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| 6. |
- Mohammed, Mohsin, et al.
(författare)
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Microelectrode clusters enable therapeutic deep brain stimulation without noticeable side-effects in a rodent model of Parkinson's disease
- 2022
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Ingår i: Journal of Neuroscience Methods. - : Elsevier BV. - 0165-0270. ; 365
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Tidskriftsartikel (refereegranskat)abstract
- Background: Deep Brain Stimulation (DBS) is an established treatment for motor symptoms in Parkinson's disease (PD). However, side effects often limit the usefulness of the treatment. New method: To mitigate this problem, we developed a novel cluster of ultrathin platinum-iridium microelectrodes (n = 16) embedded in a needle shaped gelatin vehicle. In an established rodent PD-model (6-OHDA unilateral lesion), the clusters were implanted in the subthalamic area for up to 8 weeks. In an open field setting, combinations of microelectrodes yielding therapeutic effects were identified using statistical methods. Immunofluorescence techniques were used for histological assessments of biocompatibility. Results: In all rats tested (n = 5), we found subsets of 3–4 microelectrodes which, upon stimulation (160 Hz, 60 μs pulse width, 25–40 μA/microelectrode), prompted normal movements without noticeable side effects. Other microelectrode subsets often caused side effects such as rotation, dyskinesia and tremor. The threshold (per microelectrode) to elicit normal movements strongly depended on the number of activated microelectrodes in the selected subset. The histological analysis revealed viable neurons close to the electrode contacts, minor microglial and astrocytic reactions and no major changes in the vasculature, indicating high biocompatibility. Comparison to existing methods and conclusion: By contrast to the continuous and relatively large stimulation fields produced by existing DBS electrodes, the developed microelectrode cluster enables a fine-tuned granular and individualized microstimulation. This granular type of stimulation pattern provided powerful and specific therapeutic effects, free of noticeable side effects, in a PD animal model.
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| 7. |
- Pettersson, Lina M E, et al.
(författare)
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Altered behavioural responses and functional recovery in rats following sciatic nerve compression and early vs late decompression
- 2016
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Ingår i: Journal of Plastic Surgery and Hand Surgery. - 2000-656X. ; 50:6, s. 321-330
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of the study was to examine sensory behaviour and functional recovery in rats during nerve compression and after decompression. Compression injury is a far more common condition than nerve transection. The condition is characterised by numbness and a tingling/burning sensation, and some patients experience pain and allodynia during compression or after decompression treatment. The aetiology is in many cases unknown. Thus, further studies are of great importance for the understanding of this condition. Methods: In the present study, behavioural responses to tactile stimulation, thermal pain, as well as functional sensorimotor behaviour were investigated in rats before, during severe compression, and after decompression. The sciatic nerve of the rats was experimentally compressed for 3 or 28 days, whereafter surgical release, i.e. decompression, of the nerve was performed and the rats were examined up to ∼9 weeks. Results: An altered behaviour was found in response to compression injury, which is mitigated after early decompression treatment. Conclusions: These findings indicate that early intervention during severe compression injuries is of great importance for recovery and restoration of nerve function and, thus, should have an impact on clinical routines regarding treatment of compression injuries.
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