Spinal cord repair: from experimental models to human application

Fawcett, James W.

doi:10.1038/sj.sc.3100769

Cited by 72 publications

(50 citation statements)

References 20 publications

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“…These species have also been extensively investigated because the neurobiological information obtained may hold the key to regeneration in mammals. [31][32][33] Fawcett 34 has analyzed the neurobiological basis for the absence of central axonal regeneration and has considered what may be done to overcome this deficiency. He reviews the successful experiments in which some central axonal regeneration has been achieved as follows.…”

Section: The Autonomic Motor Systemmentioning

confidence: 99%

“…The same applies to the proteoglycans related to astrocyte and oligodendrocyte precursors, against which no blocking mechanism has been discovered. 34 Grafts and transplants Going further neuroscientists have explored the possibility of replacing the lost tissue with embryonic and fetal grafts. These experiments have had variable results, some quite encouraging.…”

Section: The Autonomic Motor Systemmentioning

confidence: 99%

“…Treatment plan for human SCI Fawcett 34 has laid out a treatment plan for applying the discoveries in neurobiology, which bring about axonal regeneration in human SCI. This protocol was developed before stem cell technology became available.…”

Section: The Futurementioning

confidence: 99%

“…This procedure will require expert microsurgery painstakingly undertaken to avoid damaging residual spinal cord parenchyma with its axonal fibers. Fawcett 34 suggests that a bridge of Schwann cells and OEC derived from the patient's own tissue and expanded in culture be applied to the lesion. Axonal regeneration may be stimulated by trophic factors together with blocking molecules infused through an indwelling catheter.…”

Section: The Futurementioning

confidence: 99%

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Neuropathology: the foundation for new treatments in spinal cord injury

2004

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The first step essential in the search for a cure of human spinal cord injury (SCI) is to appreciate the complexity of the disorder. In this regard, it is not only the loss of ambulation but the sensory and autonomic changes that are equally important in recovery. In addition, there are the serious social emotional psychological and lifestyle effects of SCI which should also be taken into account. It is also true that no two SCI lesions are alike as each is the result of a SCI unique to that individual. Clinically of utmost importance is the segmental level of injury and whether it is complete, incomplete or discomplete (loss of all neurological functions below the injury but with physiological or anatomical continuity of Central nervous system tracts across the lesion). We are not concerned here with primary and secondary prevention or methods designed to limit the severity of the lesion after the event, important as they are, but with the requirements for a cure. Clearly, the greater the number of nerve fibers that can be preserved in the acute stage, the better will be the end result. Our focus at present is on the end-stage lesion with the aim of showing that a cure for SCI will depend upon establishing functionally useful central axonal regeneration and reestablishing physiological reconnections. Existing experimental methods are based on stimulating axonal regeneration by neutralizing inhibitory factors, adding positive trophisms and creating a permissive environment. Better results are obtained by bridging the gap with grafts of peripheral nerves or transplants of Schwann cells and genetically engineered fibroblasts. Recently, the potential for stem cells to enhance this process has created great interest. This is because of the ability of pluripotential cells to differentiate into neural tissue. A cure based on the physiopathology of SCI requires pyramidal, extrapyramidal, sensory, cerebellar and autonomic pathways to be regenerated with their appropriate neurotransmitters restored and reflexes integrated physiologically and in synchrony. In human SCI, there is a very long distance anatomically for axonal regrowth to occur in order to reach their relevant nuclei. This is because of continuing Wallerian degeneration. It also presumes that the target neurons are intact and that there has been no transneuronal degeneration above or below the lesion. Alternatively, in place of regenerated long axons, a multisynaptic pathway may be constructed from stem cells that have developed into neurons. Whether such a pathway would restore useful neurological functions is unknown. At present, the transplant and grafting research teams are exploring these possibilities in experimental animals. Moderate success in gaining axonal regeneration has been reported; however, it must be appreciated that the human lesion differs considerably from that of the experimental animal. In order to be successful, the neuropathology and neurophysiology of human SCI must be taken into account. The purpose of this review is to place the req...

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Section: The Autonomic Motor Systemmentioning

confidence: 99%

Section: The Autonomic Motor Systemmentioning

confidence: 99%

Section: The Futurementioning

confidence: 99%

Section: The Futurementioning

confidence: 99%

See 2 more Smart Citations

Neuropathology: the foundation for new treatments in spinal cord injury

2004

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“…2,4 ± 7 The early phase of secondary tissue destruction a ects neuronal as well as glial cell populations. 2,4,8,9 Later, a dense gliotic scar develops, inhibiting axon regeneration in addition to the endogenously present myelinassociated neurite growth inhibitory constituents. 2,10 Although di erent glial cells participate in the scar formation, the reactive astrocytes play a predominant role re¯ected by the very high levels of glial acid ®brillary protein (GFAP).…”

Section: Introductionmentioning

confidence: 99%

Protective effects of oral creatine supplementation on spinal cord injury in rats

et al. 2002

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Study design: To evaluate a potential protective e ect of increased creatine levels in spinal cord injury (SCI) in an animal model. Objectives: Acute SCI initiates a series of cellular and molecular events in the injured tissue leading to further damage in the surrounding area. This secondary damage is partly due to ischemia and a fatal intracellular loss of energy. Phospho-creatine in conjunction with the creatine kinase isoenzyme system acts as a potent intracellular energy bu er. Oral creatine supplementation has been shown to elevate the phospho-creatine content in brain and muscle tissue, leading to neuroprotective e ects and increased muscle performance. Setting: Zurich, Switzerland. Methods: Twenty adult rats were fed for 4 weeks with or without creatine supplemented nutrition before undergoing a moderate spinal cord contusion. Results: Following an initial complete hindlimb paralysis, rats of both groups substantially recovered within 1 week. However, creatine fed animals scored 2.8 points better than the controls in the BBB open ®eld locomotor score (11.9 and 9.1 points respectively after 1 week; P=0.035, and 13 points compared to 11.4 after 2 weeks). The histological examination 2 weeks after SCI revealed that in all rats a cavity had developed which was comparable in size between the groups. In creatine fed rats, however, a signi®cantly smaller amount of scar tissue surrounding the cavity was found. Conclusions: Thus creatine treatment seems to reduce the spread of secondary injury. Our results favour a pretreatment of patients with creatine for neuroprotection in cases of elective intramedullary spinal surgery. Further studies are needed to evaluate the bene®t of immediate creatine administration in case of acute spinal cord or brain injury.

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