Axons from CNS neurones regenerate into PNS grafts

Richardson, P. M.; McGuinness, U. M.; Aguayo, Albert J.

doi:10.1038/284264a0

Cited by 885 publications

(401 citation statements)

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“…Grafting of peripheral nerve to the CNS dates back at least as far as the work of Ramón y Cajal in 1911 [34,35]. Sugar and Gerard [36] demonstrated anatomical and physiological evidence of regeneration in the spinal cord through peripheral nerve grafts in 1940, though it was the work of Aguayo and colleagues that demonstrated a clear capacity for spinal cord regeneration through a peripheral graft using modern tracing methods [37,38]. These studies demonstrated that (for at least some cell populations) lesioned CNS neurons are capable of regeneration if the injured CNS is grafted with a substrate permissive to growth.…”

Section: Provision Of Growth-promoting Substrates To Sites Of Injurymentioning

confidence: 99%

Neurotrophins: Potential Therapeutic Tools for the Treatment of Spinal Cord Injury

Hollis

Tuszynski

2011

Neurotherapeutics

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Spinal cord injury permanently disrupts neuroanatomical circuitry and can result in severe functional deficits. These functional deficits, however, are not immutable and spontaneous recovery occurs in some patients. It is highly likely that this recovery is dependent upon spared tissue and the endogenous plasticity of the central nervous system. Neurotrophic factors are mediators of neuronal plasticity throughout development and into adulthood, affecting proliferation of neuronal precursors, neuronal survival, axonal growth, dendritic arborization and synapse formation. Neurotrophic factors are therefore excellent candidates for enhancing axonal plasticity and regeneration after spinal cord injury. Understanding growth factor effects on axonal growth and utilizing them to alter the intrinsic limitations on regenerative growth will provide potent tools for the development of translational therapeutic interventions for spinal cord injury.Keywords Neurotrophin . spinal cord injury . regeneration . axon plasticity . functional recovery Human Spinal Cord InjuryTraumatic injury of the spinal cord can produce a range of debilitating effects and permanently alter the capabilities and quality of life of its surviving victims. Damage to the central nervous system (CNS) in general results in destruction of neuronal circuitry. Contusion, compression, and penetration injuries of the spinal cord can interrupt the flow of sensory and motor information between the brain and periphery [1]. Depending on the location and severity of the injury, deficits can range from weakness of limb movement to total paralysis and ventilator-assisted respiration. Spontaneous functional recovery is limited, but can and often does occur in patients with initial sparing of sensorimotor function [2]. This recovery, which plateaus between 12 to 18 months, is very likely due to sparing and sprouting of axons within the zone of partial preservation, an area where some motor function remains intact, immediately adjacent to the lesion site [2].Approximately 40% of humans that sustain spinal cord injury (SCI) exhibit improvement from their early postinjury baseline, and this spontaneous recovery can range from modest to extensive [2]. Spontaneous recovery primarily appears to depend on the extent of tissue sparing at the injury site, allowing compensatory axonal sprouting and systems reorganization at levels ranging from the spinal cord to the cerebral cortex [3][4][5][6][7][8][9][10]. However, in cases of more severe injuries, means of enhancing endogenous levels of axonal sprouting and inducing true axonal regeneration are required to enhance functional outcomes.Electronic supplementary material The online version of this article

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Section: Provision Of Growth-promoting Substrates To Sites Of Injurymentioning

confidence: 99%

Neurotrophins: Potential Therapeutic Tools for the Treatment of Spinal Cord Injury

Hollis

Tuszynski

2011

Neurotherapeutics

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“…These cells appeared in sections closely associated with the regenerating fibres, and escorting these fibres through the empty spaces or through the graft tissue. Cells of the graft tissue may have another favourable function, by clearing the debries from tissue damage in the spinal cord transec tion (Richardson et al, 1980). Another important, possible role for the Schwann cells, is that they act as a trophic agent for the growing cones of the nerves.…”

Section: Discussionmentioning

confidence: 99%

Spinal cord regeneration: new experimental approach

Khalili

Hamash

1988

Spinal Cord

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SummaryAn experimental study was conducted to enhance regeneration in the spinal cord. Twenty Swiss albino rats were used, of which 8 were controls, and hemicordotomy was performed at mid-thoracic level. In 12 rats a segment of peripheral nerve (sciatic) autograft was taken, minced and implanted in the hemicordotomy site.All the rats were sacrificed at 4-12 weeks. Fixation was carried out by intracar diac perfusion of fixative. Light microscopy was used to study the hemicordotomy site. Two observations were made; first, regeneration of the cord was greatly en hanced, and second, the spinal cord caudal to the hemicordotomy did not disintegrate in the grafted cords. Key words: Experimental spinal cord implants; Spinal cord injury.Injury to the central nervous system which results in cell and tissue damage is always followed by a degree of degeneration. Regeneration in the central nervous system is known to be significantly limited (Windle, 1981). However researchers have studied the regeneration process in laboratory animals (Cajal, 1928;Collins 1983; Gerard and Kapponyi, 1926;Kao, 1970;Verra, 1981).Gerard and Kapponyi in 1926 studied regeneration of spinal cord in rat fetuses. Subsequently, research to enhance regeneration has increased (French, 1962;Hughes, 1984;Meinecke, 1985; Wilson, 1984).It was Cajal, in 1914 andin 1928, who first suggested that implantation of pieces of peripheral nerve into wounds in the central nervous system, might result in some regeneration activity. Sugar and Gerard in 1940 implanted pieces of peripheral nerves into wounds in the central nervous system of immature animals, and found a definite tendency to regeneration.More recently this regeneration phenomenon has been further studied by many workers (Aihara, 1970;Kao, 1974;Kao et al., 1970 Kao et al., , 1977a Kao et al., , 1977b. They grafted nervous tissues from the cerebellum, nodose ganglion and sciatic nerve into the transected spinal cord.Their results indicated that grafted peripheral nerve tissue enhanced the regeneration ability in the spinal cord, more than other types of tissue. SPINAL CORD REGENERATION: NEW EXPERIMENTAL APPROACH 311In this study, a sciatic nerve autograft was used in rats, but a different technique from Kao's was applied. In his work, Kao used the sciatic nerve segment (in experiments on dogs) with strict orientation of proximal/distal ends of the transplanted sciatic nerve segments (Kao, 1974).The objective in this study was to disregard orientation of the grafted nerve segment, because graft orientation is technically difficult during surgery and to maintain after surgery in spite of the use of plasma gel. The method was to mince the nerve segment and to use the material as a graft. Hence the technique was more simple and reproducible. The results obtained were comparable to those obtained by Kao. Materials and methodsTwenty adult Swiss albino rats were used in this study. The first group (controls) included 8 rats in which hemicordotomy was done without grafting. In the second group (12 rats), hemicor...

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“…The turning point came in the year 1928, when Ramon Y. Cajal’s (Lobato, 2008) work suggested that the regenerative capacity of neurons, though limited, could exist beyond their physical being and depended on the environment surrounding them. That the manipulation of the restrictive environment surrounding the neuron could aid the regenerative process was conclusively established by Aguayo and colleagues (Richardson et al, 1980). Since then, various strategies have been employed to target the different phases of regeneration which include: cell-replacement and augmenting endogenous neurogenesis, the use of trophic factors, reversal of the inhibitory cues, and induction of signaling pathways that stimulate axon growth and guidance (Horner and Gage, 2000).…”

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confidence: 86%