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- Nordblom, Jonathan
(författare)
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A regeneration strategy for spinal cord injury
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A severe traumatic spinal cord injury (SCI) frequently leads to a devastating and permanent disability. Due to glial scarring and an inhibitory local environment, regrowth of disrupted axons in the injured spinal cord beyond a lesion is obstructed, thus preventing reconnection with neurons at the other side. Many experimental strategies have been presented to limit the damage and improve outcome after SCI, but few options are available for the patient. Neurons in the central nervous system may regenerate using a growth permissive medium, such as peripheral nerve grafts. This capacity has been used to bridge a spinal cord gap by facilitating regeneration of long tracts in the spinal cord through transplanted peripheral nerve grafts, aimed at redirecting the regenerating axons into growth permissive grey matter on the other side of the injury. This principle was demonstrated in 1996, when surgical transplantations combined with adjuvant acidic fibroblastic growth factor (FGF1) led to partial recovery of hind limb function. The aim of this thesis was to develop a reproducible microsurgical method for precise placement of peripheral nerve grafts (PNGs), construct a biodegradable graft holder, assess the effect of controlled delivery of FGF1, evaluate potential regeneration of corticospinal tracts after spinal cord repair and investigate if it is possible to determine the cranial and caudal injury borders in patients with chronic and complete spinal cord injury. Our experiments in the adult rat demonstrate that replacing a section of thoracic spinal cord with a graft holder filled with peripheral nerves induced a spinal cord regeneration of various axonal types, including corticospinal axons. Further, we provide evidence of axonal ingrowth into the caudal spinal cord by anterograde neural pathway tracing and electrophysiological studies. This regeneration induced a functional improvement and robust electrophysiological response in the hind limbs, paced-up by the addition of graded doses of FGF1. The thesis also demonstrates that the cranial and caudal injury borders of patients with thoracic chronic and complete SCI can be diagnosed with high accuracy, which may be important for future diagnosis in spinal cord injury. In conclusion, we present a regeneration strategy for the transected spinal cord, primarily through the use of a biodegradable graft holder filled with individually directed peripheral nerve grafts in combination with FGF1.
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- Nordblom, Jonathan, et al.
(författare)
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FGF1 containing biodegradable device with peripheral nerve grafts induces corticospinal tract regeneration and motor evoked potentials after spinal cord resection
- 2012
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Ingår i: Restorative Neurology and Neuroscience. - 0922-6028 .- 1878-3627. ; 30:2, s. 91-102
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Repairing the spinal cord with peripheral nerve grafts (PNG) and adjuvant acidic fibroblast growth factor (FGF1) has previously resulted in partial functional recovery. To aid microsurgical placement of PNGs, a graft holder device was previously developed by our group. In hope for a translational development we now investigate a new biodegradable graft holder device containing PNGs with or without FGF1.Methods: Rats were subjected to a T11 spinal cord resection with subsequent repair using twelve white-to-grey matter oriented PNGs prepositioned in a biodegradable device with or without slow release of FGF1. Animals were evaluated with BBB-score, electrophysiology and immunohistochemistry including anterograde BDA tracing.Results: Motor evoked potentials (MEP) in the lower limb reappeared at 20 weeks after grafting. MEP responses were further improved in the group treated with adjuvant FGF1. Reappearance of MEPs was paralleled by NF-positive fibers and anterogradely traced corticospinal fibers distal to the injury. BBB-scores improved in repaired animals.Conclusions: The results continue to support that the combination of PNGs and FGF1 may be a regeneration strategy to reinnervate the caudal spinal cord. The new device induced robust MEPs augmented by FGF1, and may be considered for translational research.
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- Åberg, Jonas, et al.
(författare)
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Calcium sulphate spinal cord scaffold : a study on degradation and fibroblast growth factor 1 loading and release
- 2012
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Ingår i: Journal of biomaterials applications. - : SAGE Publications. - 0885-3282 .- 1530-8022. ; 26:6, s. 667-685
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Tidskriftsartikel (refereegranskat)abstract
- Currently, there is no regenerative strategy for the spinal cord that is part of clinical standard of core. Current paths usually include combinations of scaffold materials and active molecules. In a recent study, a permanent dental resin scaffold for treatment of spinal cord injury was designed. The results from studies on rats were promising. However, for potential clinical use, a biodegradable scaffold material that facilitates drug delivery and the regeneration of the spinal cord needs to be developed. Also a biodegradable material is expected to allow a better evaluation of the efficacy of the surgical method. In this article, the suitability of hardened calcium sulfate cement (CSC) for use as degradable spinal cord scaffolds is investigated in bench studies and in vitro studies. Compressive strength, degradation and microstructure, and the loading capability of heparin-activated fibroblast growth factor 1 (FGF1) via soaking were evaluated. The CSC could easily be injected into the scaffold mold and the obtained scaffolds had sufficient strength to endure the loads applied during surgery. When hardened, the CSC formed a porous microstructure suitable for loading of active substances. It was shown that 10 min of FGF1 soaking was enough to obtain a sustained active FGF1 release for 20–35 days. The results showed that CSC is a promising material for spinal cord scaffold fabrication, since it is biodegradable, has sufficient strength, and allows loading and controlled release of active FGF1.
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