Brain-derived neurotrophic factor prevents the death of motoneurons in newborn rats after nerve section

Sendtner, Michael; Holtmann, Bettina; Kolbeck, Roland; Thoenen, H.; Barde, Yves‐Alain

doi:10.1038/360757a0

Cited by 686 publications

(399 citation statements)

References 22 publications

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“…Transplantation of Schwann cells into sites of CNS injury, including the lesioned spinal cord, mimics the effects of peripheral nerve grafts and supports axonal regeneration [42,43]. In addition to potentially myelinating regenerated axons, Schwann cells express cell adhesion molecules, produce components of the extracellular matrix, and secrete multiple neurotrophic factors [44][45][46][47][48][49][50][51][52][53]. Whether grafted Schwann cells provide an advantage in comparision with other potential cell grafts remains to be determined; however, as the grafted cells survive poorly in the lesioned spinal cord, they are soon replaced by migrating endogenous Schwann cells [54,55].…”

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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“…However, when it became apparent that the mRNAs of BDNF, NT-3, and NT-4 / 5 are expressed in rat skeletal muscle during embryonic development and also adulthood (9,36,55), that the signal-transducing units mediating the effects of BDNF, NT-3, and NT-4/5, namely trkB and trkC, are expressed by motoneurons (26,34), and that the specific retrograde axonal transport of labelled BDNF and NT-3 was demonstrated (18), a reevaluation of the negative results obtained in vitro with chick motoneurons was mandatory. Indeed, independently four laboratories demonstrated an in vivo effect of BDNF on motoneurons (45,78,96,107). The administration of recombinant BDNF on the chick embryo chorioallantoic membrane resulted in an increased survival of spinal motoneurons (78) and, in newborn rats, the loss of motoneurons following lesion (sciatic or facial nerve) could be prevented by the local administration of recombin ant BDNF (45,96,107) .…”

Section: Neurotrophic Effects Of Members Of the Ngf Gene Familymentioning

confidence: 99%

“…Indeed, independently four laboratories demonstrated an in vivo effect of BDNF on motoneurons (45,78,96,107). The administration of recombinant BDNF on the chick embryo chorioallantoic membrane resulted in an increased survival of spinal motoneurons (78) and, in newborn rats, the loss of motoneurons following lesion (sciatic or facial nerve) could be prevented by the local administration of recombin ant BDNF (45,96,107) . Moreover, in the facial ne rve lesion paradigm, a lso NT -3 was found to have a rescue effect which, however, was smaller than that of BDNF (96).…”

Section: Neurotrophic Effects Of Members Of the Ngf Gene Familymentioning

confidence: 99%

“…The administration of recombinant BDNF on the chick embryo chorioallantoic membrane resulted in an increased survival of spinal motoneurons (78) and, in newborn rats, the loss of motoneurons following lesion (sciatic or facial nerve) could be prevented by the local administration of recombin ant BDNF (45,96,107) . Moreover, in the facial ne rve lesion paradigm, a lso NT -3 was found to have a rescue effect which, however, was smaller than that of BDNF (96). Very recently, a neuron rescue effect has also been observed in lesioned facial motoneurons after the administration of NT-4 (39 …”

Section: Neurotrophic Effects Of Members Of the Ngf Gene Familymentioning

confidence: 99%

“…In this context, it should be emphasized that, according to currently available information, there is not a single human or animal degenerative disease of the nervous system which can causally be linked to an insufficient or false (mutated) production of neurotrophic molecule (98). However, neurotrophic molecules have been demonstrated to rescue specific neurons from the consequences of a variety of mechanical (axotomy) or chemical (6-hydroxydopamine, MPTP, excitotoxic amino acids) damages (40,45,50,79,93,96,104,107). Therefore, the use of neurotrophic molecules in the treatment of degenerative diseases ofthe nervous system is a symptomatic one and strongly encourages further investigations aimed at a molecular understanding of the pathogenetic mechanisms of degenerative disorders of the nervous system.…”

Section: Introductionmentioning

confidence: 99%

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