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- Kvist, Martin, et al.
(författare)
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Costimulation blockade in transplantation of nerve allografts: long-term effects.
- 2008
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Ingår i: Journal of the Peripheral Nervous System. - : Wiley. - 1529-8027 .- 1085-9489. ; 13:3, s. 200-207
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Tidskriftsartikel (refereegranskat)abstract
- Costimulation blockade can prevent rejection of nerve allografts in short-term studies. We tested if costimulation blockade also prevented rejection of nerve allografts in long-term experiments, thereby improving functional recovery. A 7-mm sciatic nerve defect in C57/BL6 mice was bridged either by nerve allografts from Balb/C mice or by isogenic nerve grafts (isografts) from C57/BL6 mice. Costimulation blockade in the form of a triple treatment with anti-LFA-1, anti-CD40L, and CTLA4Ig was given at post-operative days 0, 2, 4, and 6 (intraperitoneal). Control mice (placebo; allografts) with nerve grafts were treated with isotype antibodies during the same time period. After 49 days, tetanic muscle force, wet weight of gastrocnemius muscle, histology, and morphometry in the tibial nerve were evaluated. Costimulation blockade diminished rejection of the nerve allografts. Axons bridged the graft. Treatment increased wet weight of the gastrocnemius muscle and resulted in a higher mean myelin area/nerve fiber in the tibial nerve distal to the nerve grafts. Tetanic muscle force and number of axons in tibial nerve showed no differences between groups. We conclude that rejection is suppressed by costimulation blockade. Treatment improves recovery of target muscle and myelination after nerve allografting.
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| 2. |
- Kvist, Martin, et al.
(författare)
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Immunomodulation by costimulation blockade inhibits rejection of nerve allografts
- 2007
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Ingår i: Journal of the Peripheral Nervous System. - : Wiley. - 1085-9489 .- 1529-8027. ; 12:2, s. 83-90
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate if costimulation blockade could be used to modulate the immune response, to prevent rejection, and to stimulate regeneration into nerve allografts. Nerve allografts from Balb/C mice, and isogenic nerve grafts (isografts) from C57/BL6 mice, were used to bridge a 7-mm gap of the sciatic nerve in C57/BL6 mice. Allograft recipients were treated with either a triple treatment with anti-lymphocyte function antigen-1 (anti-LFA), anti-CD40 ligand (anti-CD40L), and cytotoxic T-lymphocyte antigen 4 immunoglobulin (anti-CTLA4Ig) or isotype antibodies (placebo) at postoperative days 0, 2, 4, and 6 (intraperitoneal). After 5 or 9 days, the nerve grafts, together with the proximal and the distal nerve segments, were evaluated by histology and immunocytochemistry for inflammatory cells [CD4-positive (CD4+) and CD8-positive (CD8+) staining cells] and axonal outgrowth (neurofilaments). The immune response was inhibited by costimulation blockade with less extensive inflammation and a lower number of CD4+ staining cells in triple-treated allografts at 9 days. The regeneration rate was significantly faster in isografts (0.75 mm/day) compared with allografts with placebo treatment (0.39 mm/day), but not when compared with triple-treated allografts (0.49 mm/day). At 9 days, the axons were significantly longer in nerve isografts than in nerve allografts, irrespective of treatment. Hence, costimulation blockade neither increased the regeneration rate nor the outgrowth length in triple-treated allografts. We conclude that costimulation blockade inhibits the immune response in nerve allografts without deterring early axonal outgrowth.
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| 3. |
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| 4. |
- Bontioti, Eleana, et al.
(författare)
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End-to-side nerve repair in the upper extremity of rat.
- 2005
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Ingår i: Journal of the Peripheral Nervous System. - : Wiley. - 1085-9489 .- 1529-8027. ; 10:1, s. 58-68
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Tidskriftsartikel (refereegranskat)abstract
- The end-to-side nerve-repair technique, i.e., when the distal end of an injured nerve is attached end-to-side to an intact nerve trunk in an attempt to attract nerve fibers by collateral sprouting, has been used clinically. The technique has, however, been questioned. The aim of the present study was to investigate end-to-side repair in the upper extremity of rats with emphasis on functional recovery, source, type, and extent of regenerating fibers. End-to-side repair was used in the upper limb, and the radial or both median/ulnar nerves were attached end-to-side to the musculocutaneous nerve. Pawprints and tetanic muscle force were used to evaluate functional recovery during a 6-month recovery period, and double retrograde labeling was used to detect the source of the regenerated nerve fibers. The pawprints showed that, in end-to-side repair of either one or two recipient nerves, there was a recovery of toe spreading to 60-72% of the preoperative value (lowest value around 47%). Electrical stimulation of the end-to-side attached radial or median/ulnar nerves 6 months after repair resulted in contraction of muscles in the forearm innervated by these nerves (median tetanic muscle force up to 70% of the contralateral side). Retrograde labeling showed that both myelinated (morphometry) sensory and motor axons were recruited to the end-to-side attached nerve and that these axons emerged from the motor and sensory neuronal pool of the brachial plexus. Double retrograde labeling indicated that collateral sprouting was one mechanism by which regeneration occurred. We also found that two recipient nerves could be supported from a single donor nerve. Our results suggest that end-to-side repair may be one alternative to reconstruct a brachial plexus injury when no proximal nerve end is available.
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| 8. |
- Gustavsson, Per, et al.
(författare)
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Galectin-3 inhibits Schwann cell proliferation in cultured sciatic nerve
- 2007
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Ingår i: NeuroReport. - 1473-558X. ; 18:7, s. 669-673
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Tidskriftsartikel (refereegranskat)abstract
- The production of galectin-3, a carbohydrate-binding mammalian lectin, is upregulated in Schwann cells after peripheral nerve injury in areas where Schwann cells proliferate. Here we tested if galectin-3 affected proliferation of Schwann cells in cultured sciatic nerve segments. Galectin-3 significantly decreased the number of bromodeoxyuridine-labelled Schwann cell nuclei. Neither lactose nor a synthetic inhibitor directed against the carbohydrate-binding region abolished the effects of galectin-3. In addition, a mutant galectin-3 unable to bind endogenous carbohydrates had similar effects as normal galectin-3. We conclude that galectin-3 reduces proliferation of Schwann cells in cultured sciatic nerve segments by a mechanism which is independent of its carbohydrate-binding moiety.
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| 9. |
- Gustavsson, Per, et al.
(författare)
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Neurite guidance on protein micropatterns generated by a piezoelectric microdispenser
- 2007
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Ingår i: Biomaterials. - : Elsevier BV. - 1878-5905 .- 0142-9612. ; 28:6, s. 1141-1151
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we developed a microdispenser technique in order to create protein patterns for guidance of neurites from cultured adult mouse dorsal root ganglia (DRG). The microdispenser is a micromachined silicon device that ejects 100 picolitre droplets and has the ability to position the droplets with a precision of 6-8 mu m. Laminin and bovine serum albumin (BSA) was used to create adhesive and non-adhesive protein lines on polystyrene surfaces (cell culture dishes). Whole-mounted DRGs were then positioned close to the patterns and neurite outgrowth was monitored. The neurites preferred to grow on laminin lines as compared to the unpatterned plastic. When patterns were made from BSA the neurites preferred to grow in between the lines on the unpatterned plastic surface. We conclude that microdispensing can be used for guidance of sensory neurites. The advantages of microdispensing is that it is fast, flexible, allows deposition of different protein concentrations and enables patterning on delicate surfaces due to its non-contact mode of operation. It is conceivable that microdispensing can be utilized for the creation of protein patterns for guiding neurites to obtain in vitro neural networks, in tissue engineering or rapid screening for guiding proteins. (c) 2006 Elsevier Ltd. All rights reserved.
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| 10. |
- Hällström, Waldemar, et al.
(författare)
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Gallium phosphide nanowires as a substrate for cultured neurons
- 2007
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Ingår i: Nano Letters. - : American Chemical Society (ACS). - 1530-6992 .- 1530-6984. ; 7:10, s. 2960-2965
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Tidskriftsartikel (refereegranskat)abstract
- Dissociated sensory neurons were cultured on epitaxial gallium phosphide (GaP) nanowires grown vertically from a gallium phosphide surface. Substrates covered by 2.5 mu m long, 50 nm wide nanowires supported cell adhesion and axonal outgrowth. Cell survival was better on nanowire substrates than on planar control substrates. The cells interacted closely with the nanostructures, and cells penetrated by hundreds of wires were observed as well as wire bending due to forces exerted by the cells.
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