Neurotrophic Factors Increase Axonal Growth after Spinal Cord Injury and Transplantation in the Adult Rat

Bregman, Barbara S.; McAtee, Marietta; Dai, Hai Ning; Kuhn, Penelope L.

doi:10.1006/exnr.1997.6705

Cited by 343 publications

(199 citation statements)

References 74 publications

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“…20,34 Recently, Bahr and Schwab 2 showed that regenerating axons regain some of their developing stage characteristics and may also rely on both cues to re-innervate their targets. This view was shared by Woolford, 47 and more recently this concept was echoed by Houwelling et al 21 and Bregman et al, 6 who demonstrated experimentally that neurotrophic factors were able to exert a neurotropic in¯uence on injured, mature CNS axons.…”

Section: Discussionmentioning

confidence: 90%

Defining the concentration gradient of nerve growth factor for guided neurite outgrowth

2001

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Section: Discussionmentioning

confidence: 90%

Defining the concentration gradient of nerve growth factor for guided neurite outgrowth

2001

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“…Such capability may be enhanced by molecular genetic manipulation whereby the introduced stem cells may be engineered to express trophic factors as has been done experimentally. 72,73 These axonal endings may be some distance away due to Wallerian degeneration. It will be necessary for these stimulating factors to be transported to the respective cell bodies, Betz cells above, posterior horn neurons and root ganglia below the lesion site in order to bring this about.…”

Section: The Futurementioning

confidence: 99%

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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“…[151][152][153] Additionally, BDNF and NT-3 enhanced growth of supraspinal and propriospinal axons into Schwann cellseeded guidance channels in vivo, 154 and boosted growth of descending axons into fetal transplants. 155 Recently, NT-3 was reported to promote regeneration of dorsal column sensory axons into and beyond a graft of bone marrow stromal cells, but only when these neurons were preconditioned by cAMP injection into the DRG. 156 Fewer studies have shown that treatment with neurotrophic factors on their own can induce axonal regeneration within the damaged spinal cord; however, intrathecally delivered NT-3 can induce regeneration of injured dorsal column axons.…”

Section: Myelin and Myelin Signaling: An Inhibitory Chorus Linementioning

confidence: 99%

“…275 Analagous to the peripheral nerve environment, axons grow readily into grafts of fetal tissue, but emerge distally in a more limited fashion, a limitation that may be overcome by concomitant administration of neurotrophic factors. 155,276 Transplantation of fetal spinal tissue has been tested clinically in the United States in patients with progressive post-traumatic syringomyelia, and preliminary reports suggest that this treatment is safe, 277,278 although complete reports have not been published. Since the use of fetal tissue entails ethical challenges, it may need to be proven superior to other biological bridges in order to assume the role of a preferred clinical bridging intervention.…”

Section: Scs and Oecs: A Duel Or A Duet?mentioning

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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Neurotrophic Factors Increase Axonal Growth after Spinal Cord Injury and Transplantation in the Adult Rat

Cited by 343 publications

References 74 publications

Defining the concentration gradient of nerve growth factor for guided neurite outgrowth

Defining the concentration gradient of nerve growth factor for guided neurite outgrowth

Neuropathology: the foundation for new treatments in spinal cord injury

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

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