Peripheral Nerve Grafts and aFGF Restore Partial Hindlimb Function in Adult Paraplegic Rats

Lee, Yu Shang; Hsiao, Ian; Lin, Vernon W.

doi:10.1089/08977150260338001

Cited by 93 publications

(80 citation statements)

References 49 publications

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“…Also, FGF1 was added to the fibrin glue because it was shown to promote axonal regeneration and reduce neuronal death [11] and reduce axonal dieback [64]. Previous studies using rat models have demonstrated the important role of FGF1 in axonal regeneration in the injured adult spinal cord [11,64,65]. The number of NF-positive axons within both types of poly(D,L-lactic acid) foams was low compared with fibrin only implants, suggesting that the porous polymer structure supported only limited axonal ingrowth.…”

Section: Discussionmentioning

confidence: 99%

Freeze-dried poly(d,l-lactic acid) macroporous guidance scaffolds impregnated with brain-derived neurotrophic factor in the transected adult rat thoracic spinal cord

et al. 2004

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The effects of poly(D,L-lactic acid) macroporous guidance scaffolds (foams) with or without brain-derived neurotrophic factor (BDNF) on tissue sparing, neuronal survival, axonal regeneration, and behavioral improvements of the hindlimbs following implantation in the transected adult rat thoracic spinal cord were studied. The foams were embedded in fibrin glue containing acidic-fibroblast growth factor. One group of animals received fibrin glue with acidic-fibroblast growth factor only. The foams were prepared by a thermally induced polymer-solvent phase separation process and contained longitudinally oriented macropores connected to each other by a network of micropores. Both foams and fibrin only resulted in a similar gliotic and inflammatory response in the cord-implant interfaces. With BDNF foam, up to 20% more NeuN-positive cells in the spinal nervous tissue close to the rostral but not caudal spinal cord-implant interface survived than with control foam or fibrin only at 4 and 8 weeks after implantation. Semithin plastic sections and electron microcopy revealed that cells and axons more rapidly invaded BDNF foam than control foam. Also, BDNF foam contained almost twice as many blood vessels than control foam at 8 weeks after implantation. Tissue sparing was similar in all three implantation paradigms; approximately 42% of tissue was spared in the rostral cord and approximately 37% in the caudal cord at 8 weeks post grafting. The number of myelinated and unmyelinated axons was low and not different between the two types of foams. Many more axons were found in the fibrin only graft. Serotonergic axons were not found in any of the implants and none of the axons regenerated into the caudal spinal cord. The behavioral improvements in the hindlimbs were similar in all groups. These findings indicated that foam is well tolerated within the injured spinal cord and that the addition of BDNF promotes cell survival and angiogenesis. However, the overall axonal regeneration response is low. Future research should explore the use of poly(D,L-lactic acid) foams, with or without axonal growth-promoting factors, seeded with Schwann cells to enhance the axonal regeneration and myelination response.

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Section: Discussionmentioning

confidence: 99%

Freeze-dried poly(d,l-lactic acid) macroporous guidance scaffolds impregnated with brain-derived neurotrophic factor in the transected adult rat thoracic spinal cord

et al. 2004

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“…In the case of a complete transection lesion 2 pieces of tibial nerve placed into the cavity side by side are sufficient to appose most of the surface area of the injured spinal cord. Others have used multiple pieces of smaller intercostal nerves stabilized by fibrin glue to fill a complete transection lesion [39][40][41] or multiple nerve segments embedded in a pre-formed matrix [42]. In these latter situations both ends of the grafts simultaneously were apposed to the injured spinal cord, fitting between the cut ends of the complete spinal cord lesion site, allowing for bidirectional growth.…”

Section: Technical Considerations For Using a Peripheral Nerve Graftmentioning

confidence: 99%

“…This transplantation study has resulted in behavioral, electrophysiological, and anatomical improvements. Forelimb stepping, partial weight support, and movement in all three joints were observed after PNG + αFGF treatment [39,40]. Motor-evoked potentials [41,42] and somatosensory potentials [40] were recorded from animals that received this transplantation strategy.…”

Section: Experimental Approaches Using a Pngmentioning

confidence: 99%

“…Forelimb stepping, partial weight support, and movement in all three joints were observed after PNG + αFGF treatment [39,40]. Motor-evoked potentials [41,42] and somatosensory potentials [40] were recorded from animals that received this transplantation strategy. Serotonin positive fibers found in the cord caudal to the PNG indicated axonal outgrowth from the graft [41].…”

Section: Experimental Approaches Using a Pngmentioning

confidence: 99%

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Peripheral Nerve Grafts Support Regeneration after Spinal Cord Injury

et al. 2011

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Summary: Traumatic insults to the spinal cord induce both immediate mechanical damage and subsequent tissue degeneration leading to a substantial physiological, biochemical, and functional reorganization of the spinal cord. Various spinal cord injury (SCI) models have shown the adaptive potential of the spinal cord and its limitations in the case of total or partial absence of supraspinal influence. Meaningful recovery of function after SCI will most likely result from a combination of therapeutic strategies, including neural tissue transplants, exogenous neurotrophic factors, elimination of inhibitory molecules, functional sensorimotor training, and/or electrical stimulation of paralyzed muscles or spinal circuits. Peripheral nerve grafts provide a growthpermissive substratum and local neurotrophic factors to enhance the regenerative effort of axotomized neurons when grafted into the site of injury. Regenerating axons can be directed via the peripheral nerve graft toward an appropriate target, but they fail to extend beyond the distal graft-host interface because of the deposition of growth inhibitors at the site of SCI. One method to facilitate the emergence of axons from a graft into the spinal cord is to digest the chondroitin sulfate proteoglycans that are associated with a glial scar. Importantly, regenerating axons that do exit the graft are capable of forming functional synaptic contacts. These results have been demonstrated in acute injury models in rats and cats and after a chronic injury in rats and have important implications for our continuing efforts to promote structural and functional repair after SCI.

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“…Peripheral nerves are still used experimentally to examine axonal growth in response to other manipulations, and can support some return of function after complete thoracic transection (in rat) with concomitant administration of growth factors. [200][201][202] Peripheral nerves have been implanted at the site of SCI in patients in Taiwan, China, Peru, and Brazil and a report of such surgery recently became available. 203 In this case, a patient with chronic paraplegia resulting from thoracic SCI was treated 4 years following injury with autologous sural nerve grafts and acidic FGF.…”

Section: Myelin and Myelin Signaling: An Inhibitory Chorus Linementioning

confidence: 99%

Setting the stage for functional repair of spinal cord injuries: a cast of thousands

2005

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Here we review mechanisms and molecules that necessitate protection and oppose axonal growth in the injured spinal cord, representing not only a cast of villains but also a company of therapeutic targets, many of which have yet to be fully exploited. We next discuss recent progress in the fields of bridging, overcoming conduction block and rehabilitation after spinal cord injury (SCI), where several treatments in each category have entered the spotlight, and some are being tested clinically. Finally, studies that combine treatments targeting different aspects of SCI are reviewed. Although experiments applying some treatments in combination have been completed, auditions for each part in the much-sought combination therapy are ongoing, and performers must demonstrate robust anatomical regeneration and/or significant return of function in animal models before being considered for a lead role.Spinal Cord (2005) 43, 134-161.

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Peripheral Nerve Grafts and aFGF Restore Partial Hindlimb Function in Adult Paraplegic Rats

Cited by 93 publications

References 49 publications

Freeze-dried poly(d,l-lactic acid) macroporous guidance scaffolds impregnated with brain-derived neurotrophic factor in the transected adult rat thoracic spinal cord

Freeze-dried poly(d,l-lactic acid) macroporous guidance scaffolds impregnated with brain-derived neurotrophic factor in the transected adult rat thoracic spinal cord

Peripheral Nerve Grafts Support Regeneration after Spinal Cord Injury

Setting the stage for functional repair of spinal cord injuries: a cast of thousands

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