1. |
- Povlsen, Bo, et al.
(författare)
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Functional evaluation of regenerated and misrouted axons to glabrous and hairy skin of the rat hind foot after sciatic neurotomy and suture
- 1995
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886 .- 1090-2430. ; 132:1, s. 99-104
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Tidskriftsartikel (refereegranskat)abstract
- The function of misrouted regenerated polymodal nociceptor C-fibers and low-threshold mechanoreceptive axons in the lateral plantar nerve (LPN) and in the foot branch of the superficial peroneal nerve (fSPN) was evaluated 3 months after unilateral sciatic neurotomy and suture. Two weeks before evaluation the tibial fascicle (or the peroneal fascicle) above the neurotomy was cut and tied off. In this way only functional regeneration of misrouted axons was tested in the LPN (or the fSPN). In regenerated animals the glabrous skin area had no functional fSPN-related low-threshold mechanoreceptive axons. However, the hairy fSPN skin area showed function of misrouted LPN-related low-threshold mechanoreceptive axons. In both the glabrous skin domain innervated by the LPN and the hairy skin area supplied by the fSPN, functional regeneration of misrouted polymodal nociceptor C-fibers was found. We conclude that functional regeneration of misrouted axons related to polymodal nociceptive units and low-threshold mechanoreceptive units is more efficient in hairy skin of the rat foot whereas only misrouted polymodal nociceptor C-fibers recover function in glabrous skin.
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2. |
- Barry, Melissa, et al.
(författare)
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Utility of intracerebral theta burst electrical stimulation to attenuate interhemispheric inhibition and to promote motor recovery after cortical injury in an animal model
- 2014
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Ingår i: Experimental Neurology. - : Academic Press. - 0014-4886 .- 1090-2430. ; 261, s. 258-266
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Tidskriftsartikel (refereegranskat)abstract
- Following a cerebral cortex injury such as stroke, excessive inhibition around the core of the injury is thought to reduce the potential for new motor learning. In part, this may be caused by an imbalance of interhemispheric inhibition (IHI); therefore, treatments that relieve the inhibitory drive from the healthy hemisphere to the peri-lesional area may enhance motor recovery. Theta burst stimulation delivered by transcranial magnetic stimulation has been tested as a means of normalizing IHI, but clinical results have been variable. Here we use a new rat model of synaptic IHI to demonstrate that electrical intracranial theta burst stimulation causes long-lasting changes in motor cortex excitability. Further, we show that contralateral intermittent theta burst stimulation (iTBS) blocks IHI via a mechanism involving cannabinoid receptors. Finally, we show that contralesional iTBS applied during recovery from cortical injury in rats improves the recovery of motor function. These findings suggest that theta burst stimulation delivered through implanted electrodes may be a promising avenue to explore for augmenting rehabilitation from brain injury.
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3. |
- Jerregård, Helena, et al.
(författare)
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Sorting of Regenerating Rat Sciatic Nerve Fibers with Target-Derived Molecules
- 2001
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886 .- 1090-2430. ; 169:2, s. 298-306
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Tidskriftsartikel (refereegranskat)abstract
- The functional outcome of microsurgical repair of divided nerves is disappointing since many regenerating axons fail to reach appropriate targets. Sorting of regenerating axons according to target tissue might be used to improve functional regeneration. The aim of the present study is to see if regenerating axons can be sorted into functionally different bundles with target-derived molecules. The proximal stump of the adult rat sciatic nerve was sutured into the inlet of a silicon Y-tube. The two branches of the Y-tube were filled with agarose primed with filtrates prepared from skin and muscle homogenates from the operated rat. The tibial and sural nerves were inserted in the two branches of the Y-tube. Six weeks later the sciatic nerve axons showed vigorous regeneration into both branches. Electron microscopic examination of regenerated nerve segments showed numerous myelinated and unmyelinated axons. The proportion of myelinated axons was significantly larger in the muscle-gel branch than in the skin-gel branch. Retrograde tracing from the nerve regenerates with Fast Blue and Fluoro-Ruby showed that ventral horn neurons at L4–L5 segmental levels were preferentially labeled from the muscle-gel branch. Neurons in corresponding dorsal root ganglia were labeled from both Y-tube branches (no significant numerical difference). A few neurons of both types contained both tracers. Measurements revealed that sensory neurons labeled from the muscle-gel branch were significantly larger (mean perikaryal area 870 μm2) than neurons labeled from the skin-gel branch (mean area 580 μm2). We conclude that regenerating motor and sensory axons can be sorted with target-derived molecules.
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4. |
- Jiao, Yu, et al.
(författare)
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Olfactory ensheathing cells promote neurite outgrowth from co-cultured brain stem slice
- 2011
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Ingår i: EXPERIMENTAL NEUROLOGY. - : Elsevier Science B.V., Amsterdam. - 0014-4886 .- 1090-2430. ; 229:1, s. 65-71
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Tidskriftsartikel (refereegranskat)abstract
- Cell therapy aiming at the replacement of degenerated neurons is a very attractive approach. By using an established in vitro organotypic brain stem (BS) slice culture we screen for candidate donor cells, some of them being further functionally assessed in in vivo models of sensorineural hearing loss. Both in vitro and in vivo systems show that implanted cells face challenges of survival, targeted migration, differentiation and functional integration with the host tissue. Low success rates are possibly due to the lack of necessary neurotrophic factors, adhesion molecules and guiding cues. Olfactory ensheathing cells (OECs) have been shown to express a number of neurotrophic factors and to promote axonal growth through cell to cell interactions. In the present study we co-cultured OECs with organotypic BS slice in order to see if OECs can serve as a facilitator when screening candidate donor cells in an organotypic culture setup. Here we show that OECs when co-cultured with the auditory BS slice not only promote neurite outgrowth from the cochlear nucleus (CN) region of the BS slice but also support cells by having BS slice axons growing along their processes. These findings further suggest that OECs may enhance survival and targeted migration of candidate donor cells suitable for cell therapy in vitro and in vivo. This article is part of a Special Issue entitled: Understanding olfactory ensheathing glia and their prospect for nervous system repair.
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5. |
- Kanoke, Atsushi, et al.
(författare)
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The effect of type 2 diabetes on CD36 expression and the uptake of oxLDL Diabetes affects CD36 and oxLDL uptake
- 2020
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Ingår i: Experimental Neurology. - : Academic Press. - 0014-4886 .- 1090-2430. ; 334
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Tidskriftsartikel (refereegranskat)abstract
- We investigated whether type 2 diabetes mellitus (T2DM), a risk factor of stroke, affects the level of scavenger receptor CD36 and the uptake of its ligand, oxidized LDL (oxLDL); and whether pioglitazone, a drug that enhances CD36, promotes oxLDL uptake. Compared to normoglycemic db/+ mice, adult db/db mice showed a pronounced reduction in surface CD36 expression on myeloid cells from the blood, brain, and bone marrow as detected by flow cytometry, which correlated with elevated plasma soluble-CD36 as determined by ELISA. Increased CD36 expression was found in brain macrophages and microglia of both genotypes 7 days after ischemic stroke. In juvenile db/db mice, prior to obesity and hyperglycemia, only a mild reduction of surface CD36 was found in blood neutrophils, while all other myeloid cells showed no difference relative to the db/+ strain. In vivo, oral pioglitazone treatment for four weeks increased CD36 levels on myeloid cells in db/db mice. In vitro, uptake of oxLDL by bone marrow derived macrophages (BMDMs) of db/db mice was reduced relative to db/+ mice in normal glucose medium. OxLDL uptake inversely correlated with glucose levels in the medium in db/+ BMDMs. Furthermore, pioglitazone restored oxLDL uptake by BMDMs from db/db mice cultured in high glucose. Our data suggest that T2DM is associated with reduced CD36 on adult myeloid cells, and pioglitazone enhances CD36 expression in db/db cells. T2DM or high glucose reduces oxLDL uptake while pioglitazone enhances oxLDL uptake. Our findings provide new insight into the mechanism by which pioglitazone may be beneficial in the treatment of insulin resistance.
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6. |
- Kawa, Lizan, et al.
(författare)
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Expression of galanin and its receptors are perturbed in a rodent model of mild, blast-induced traumatic brain injury
- 2016
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Ingår i: Experimental Neurology. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0014-4886 .- 1090-2430. ; 279, s. 159-167
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Tidskriftsartikel (refereegranskat)abstract
- The symptomatology, mood and cognitive disturbances seen in post-traumatic stress disorder (PTSD) and mild blast-induced traumatic brain injury (mbTBI) overlap considerably. However the pathological mechanisms underlying the two conditions are currently unknown. The neuropeptide galanin has been suggested to play a role in the development of stress and mood disorders. Here we applied bio- and histochemical methods with the aim to elucidate the nature of any changes in the expression of galanin and its receptors in a rodent model of mbTBI. In situ hybridization and quantitative polymerase chain reaction studies revealed significant, injury induced changes, in some cases lasting at least for one week, in the mRNA levels of galanin and/or its three receptors, galanin receptor 1-3 (GalR1-3). Such changes were seen in several forebrain regions, and the locus coeruleus. In the ventral periaqueductal gray GalR1 mRNA levels were increased, while GalR2 were decreased. Analysis of galanin peptide levels using radioimmunoassay demonstrated an increase in several brain regions including the locus coeruleus, dorsal hippocampal formation and amygdala. These findings suggest a role for the galanin system in the endogenous response to mbTBI, and that pharmacological studies of the effects of activation or inhibition of different galanin receptors in combination with functional assays of behavioral recovery may reveal promising targets for new therapeutic strategies in mbTBI. (C) 2016 Elsevier Inc. All rights reserved.
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7. |
- Palmgren, Bjorn, et al.
(författare)
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Survival, migration and differentiation of mouse tau-GFP embryonic stem cells transplanted into the rat auditory nerve
- 2012
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Ingår i: Experimental Neurology. - : Elsevier. - 0014-4886 .- 1090-2430. ; 235:2, s. 599-609
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Tidskriftsartikel (refereegranskat)abstract
- Stem cells have been investigated as treatment for a variety of diagnoses such as Parkinsons disease, Alzheimers disease and spinal cord injuries. Here, we investigated the possibility of using stem cells as a replacement therapy for lesions of the auditory nerve (AN). We transplanted tau-GFP mouse embryonic stem cells into the AN either by the internal auditory meatus or via the modiolus in rats that had been previously deafened by application of beta-bungarotoxin to the round window niche. We investigated the effect of brain derived neurotrophic factor (BDNF) on cell transplant survival and differentiation. Additionally chondroitinase ABC (ChABC), a digestive enzyme that cleaves the core chondroitin sulfate proteoglycans, was used in order to promote possible migration of cells and axons through the transitional zone. A bioactive isoleucine-lysine-valine-alanine-valine (IKVAV) peptide amphiphile (PA) nanofiber gel was applied around the cell injection site. This nanofiber gel has been shown to promote neural differentiation and other similar gels have been used to encapsulate and release proteins. Three weeks after injection, transplanted cells were found in the scala tympani, the modiolus, the AN trunk and the brain stem. As compared to cell transplantation and gel only, BDNF content in the PA gel increased cell survival and neuronal differentiation. In the animals treated with ChABC we observed extensive migration of cells through the transitional zone to or from the CNS.
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8. |
- Regala, C., et al.
(författare)
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Xenografted fetal dorsal root ganglion, embryonic stem cell and adult neural stem cell survival following implantation into the adult vestibulocochlear nerve
- 2005
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Ingår i: Experimental Neurology. - : Elsevier. - 0014-4886 .- 1090-2430. ; 193:2, s. 326-333
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Tidskriftsartikel (refereegranskat)abstract
- Sensorineural hearing loss is a disabling condition. In the post-embryonic and adult mammalian inner ear, the regeneration of auditory hair cells, spiral ganglion neurons or their axons does not occur naturally. This decrease in excitable neurons limits the success of auditory rehabilitation.Allografts and xenografts have shown promise in the treatment of a variety of neurological diseases. Fetal dorsal root ganglion (DRG) neurons can extend functional connections in the rat spinal cord. Embryonic stem cells (ES cells) and adult neural stem cells (ANSC) have the potential to differentiate into neurons.We have implanted embryonic days (E) 13–16 fetal mouse DRGs from transgenic mouse lines that express Enhanced Green Fluorescent Protein (EGFP) or lacZ reporter genes, EGFP-expressing ES cells or lacZ-expressing ANSC into the injured vestibulocochlear nerve of adult rats and guinea pigs. Survival of the implants was assessed 2 to 4 weeks postoperatively. For further evaluation of the differentiation of the implanted ES-cells, we double labeled with the mouse-specific neuronal antibody Thy 1.2.The rats implanted with EGFP- or lacZ-expressing DRGs showed labeled DRGs after sacrifice. In addition, EGFP-positive nerve fibers were seen growing within the proximal nerve. The results from the EGFP ES cells and lacZ ANSC revealed reporter-expressing cells at the site of injection in the vestibulocochlear nerve of the host rats and guinea pigs but also within the brain stem. Thy 1.2 profiles were seen among the EGFP ES cells within the 8th cranial nerve.The findings of this study indicate that the vestibulocochlear nerve of adult rats and guinea pigs will support xenotransplants of embryonic DRG, ES cells and ANSC. This may have future clinical applicability in recreating a neuronal conduit following neuronal injury between the inner ear and the central nervous system (CNS).
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