Formation of functional endplates by spinal axons regenerating through a peripheral nerve graft. A study in the adult rat

Horvat, Jean-Claude; Pécot-Dechavassine, M; Mira, Jean‐Claude; Davarpanah, Y.

doi:10.1016/0361-9230(89)90134-2

Cited by 48 publications

(39 citation statements)

References 29 publications

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“…The grafted rootlets act by providing an environment which appears to be much more permissive to axonal growth and elongation than the surrounding injured CNS tissue of the adult animal. These ®ndings are in full agreement with previous experiments where peripheral nerve grafts (PNG) or roots were implanted into the spinal cord in adult rodents, 3,20 cats, 8 monkeys 9 or dogs. 12 In PNG implantation studies in the dog, the average number of retrogradely HRP labelled cells was about 30.…”

Section: Advantages Of the Lateral Surgical Approachsupporting

confidence: 91%

“…However, this inability for axonal regeneration cannot be considered as an intrinsic property of CNS neurons as most of them can extend an axon again along an autologous peripheral nerve segment grafted in their immediate vicinity. 1,2,3 Root reimplantation, a new surgical strategy for the treatment of brachial plexus injuries, is based on these experimental data.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, the aims of our study are: (1) to investigate, in a dog model, a lateral surgical approach for the exploration of the cranial part of the brachial plexus and reimplantation of, at least, three ventral roots in the precise area where the avulsion had taken place; (2) to evaluate whether axonal regeneration, after root avulsion and reimplantation, does occur in the dog; (3) to describe the consequences of the surgical approach, avulsion and reimplantation on dog gait.…”

Section: Introductionmentioning

confidence: 99%

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Lateral approach of the dog brachial plexus for ventral root reimplantation

et al. 1998

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A lateral surgical approach of the cervical spinal cord and brachial plexus was developed in nine dogs for avulsion and reimplantation of the ventral cervical spinal roots (C). The surgical steps involved in exposing the spinal cord and roots are described. The avulsed rootlets of C6 and C7 were reimplanted in their initial position. As a direct consequence of the avulsion, accid paralysis of the shoulder and severe amyotrophy developed within 5 ± 7 weeks on the injured side. In addition, the dogs exhibited clinical signs resulting from damage to long ®ber tracts due to the reimplantation procedure. A partial recovery of these de®cits was observed during the 6 postoperative months. Retrograde axonal tracing with horseradish peroxidase applied to the distal stump of the musculocutaneous, suprascapular, and subscapular nerves (originating from C5, C6 and C7) revealed the presence of labelled neuronal somata that were located in the ipsilateral ventral horn, close to the tip of the reimplanted rootlets. It is concluded that the dog constitutes a worthwhile animal model for the study of avulsion and reimplantation of brachial plexus root via a lateral surgical approach.

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Section: Advantages Of the Lateral Surgical Approachsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Lateral approach of the dog brachial plexus for ventral root reimplantation

et al. 1998

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“…Regrowth ceases as soon as axons contact the CNS milieu again. Various studies have demonstrated that central axons can elongate within autologous PN grafted into the spinal cord and form functional synapses with skeletal muscles, leading to motor and sensory recovery (7,(9)(10)(11). Spinal cord neurons, as well as the midbrain and brainstem neurons that originate the rubrospinal, vestibulospinal, and reticulospinal tracts, are endowed with a high capability of axonal regeneration into PN transplants (12)(13)(14)(15).…”

mentioning

confidence: 99%

Glutamatergic reinnervation through peripheral nerve graft dictates assembly of glutamatergic synapses at rat skeletal muscle

Brunelli

Spano

Barlati

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Acetylcholine is the main neurotransmitter at the mammalian neuromuscular junction (NMJ) where nicotinic acetylcholine receptors mediate the signaling between nerve terminals and muscle fibers. We show that under glutamatergic transmission, rat NMJ switches from cholinergic type synapse to glutamatergic synapse. Connecting skeletal muscle to the lateral white matter of the spinal cord by grafting the distal stump of the transected motor nerve produced functional muscle reinnervation. The restored neuromuscular activity became resistant to common curare blockers but sensitive to the glutamate ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist. Analysis of the regenerated nerve disclosed new glutamatergic axons and the disappearance of cholinergic fibers. Many axons belonged to the supraspinal neurons located in the red nucleus and the brainstem nuclei. Finally, the innervated muscle displayed high expression and clustering of ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunits glutamate receptors 1 and 2. Our data suggest that supraspinal neurons can target skeletal muscle, which retains the plasticity to generate functional glutamatergic NMJ.glutamate ͉ neuromuscular junction ͉ red nucleus T raumatic paraplegia caused by spinal cord injury is still an irreversible condition. So far, there is no medical or surgical treatment capable of curing paraplegia. The CNS is ''nonpermissive'' for the advancement of injured axons because of an abundance of growth-inhibitory molecules in the myelin and the glial scar (1-3). In addition, there are no growth-promoting factors at the neuronal growth cone or at the somata. However, when peripheral nerves (PN) are directly grafted into the CNS, central axons can progress throughout the peripheral endoneural tubes, suggesting they can regenerate in an appropriate environment (4-7). The central fibers that are diverted into a nerve graft implanted within a healthy structure derive from neurons axotomized during the grafting procedure and not from uninjured neurons spared by nerve graft implantation (8). Regrowth ceases as soon as axons contact the CNS milieu again. Various studies have demonstrated that central axons can elongate within autologous PN grafted into the spinal cord and form functional synapses with skeletal muscles, leading to motor and sensory recovery (7, 9-11). Spinal cord neurons, as well as the midbrain and brainstem neurons that originate the rubrospinal, vestibulospinal, and reticulospinal tracts, are endowed with a high capability of axonal regeneration into PN transplants (12-15). Thus, in an attempt to bypass a spinal cord lesion by connecting descending motor fibers with skeletal muscles, muscular nerve branches were inserted into the severed lateral bundle of monkey spinal cord (11). The new connection produced muscle reinnervation and restored motor function. This result raised the possibility that the regrowth of axons descending from central noncholinergic neurons and cut during the grafting procedure could be re...

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“…Studies in mouse and rat have shown that motor neurons and neurons in lamina 10 lack VGluT2, at least in the lumbar segment [70]. A previous study argued that the use of PNG in adult rats to join the SC to a nearby-denervated skeletal muscle regenerated the axons of spinal neurons, especially motor neurons and that the neuromuscular junctions were cholinergic because endplate potentials were suppressed by curare [71]. Our experiment morphologically demonstrated the capacity of spinal VGlutT2 neurons to regenerate peripheral nerve grafts and to produce endings (terminals) that innervate skeletal muscle.…”

Section: Indirect Immunofluorescencementioning

confidence: 99%

New Aspects of Graft-induced Central Plasticity and Neuroregeneration at T 10 in a Rat Model†

Wild¹,

Cătoi²,

Wild³

et al. 2017

J Neurol Neurophysiol

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Objective: Retest Brunelli's graft induced glutamate neurotransmitter switch at the neuromuscular junction in rat for the translation of new aspects of central plasticity concepts for human reconstructive surgery in spinal cord lesions. Methods:Randomized double blind controlled study in rat, which was limited to 30 animals (Charles River, 220 to 280 g). Ethical research approval was obtained from the Animal Research Committee of the University Hospital Schleswig Holstein, UK-SH, Lübeck, D, and legitimated by the Governmental Department of Agriculture, Natural Environments and Agriculture Kiel, D, in compliance with the European Commission Recommendation to retest and review of graft-induced glutamatergic regeneration and /or cholinergic co-transmission at the neuromuscular junction for reinnervation of the skeletal internal obliquus abdominal muscle fibres. Assessments were performed to demonstrate pharmacological neuromodulation after attaching the lateral corticospinal tract at T10 to the bisected skeletal motor nerve. Medication was administered for 14 days postoperatively-a) verum Cerebrolysin ® IP=12-b) shams NaCl 0.9% IP=11, and c) 7 controls (nil). 2nd Op at day 90 (16 surviving rats) for open proof of reinnervation and its type by a) CMAP, b)Vecuronium ® application. Fast Blue ® labeling were performed. 10 days later, on the 3rd Op N=15, euthanasia and organ fixation were performed. Extensive histology-morphology examinations were performed in Cluj.Results: Eight rats showed positive CMAPs. Reinnervation and neuromodulation were demonstrated by counting and comparison of the grafted muscle fibers diameter. Four CAMP-positive-rats received Vecuronium ® : 1 CERE and 1 NaCl each demonstrated a loss of amplitude respectively two an incomplete muscle blockage due to the coexistence of glutamatergic and cholinergic neurotransmission. Confirmation of the VGluT2 in axons was observed by immunofluorescence. FB+ neurons were observed in many Rexed laminae in grafted spinal cord, but not in the brain. Conclusion:The coexistence of graft-induced cholinergic and glutamatergic neurotransmission and a great capacity of lower motor neurons and other types of spinal neurons to regenerate were observed. Because of limited animals, pharmacological neuromodulation requires further investigation.

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Formation of functional endplates by spinal axons regenerating through a peripheral nerve graft. A study in the adult rat

Cited by 48 publications

References 29 publications

Lateral approach of the dog brachial plexus for ventral root reimplantation

Lateral approach of the dog brachial plexus for ventral root reimplantation

Glutamatergic reinnervation through peripheral nerve graft dictates assembly of glutamatergic synapses at rat skeletal muscle

New Aspects of Graft-induced Central Plasticity and Neuroregeneration at T 10 in a Rat Model†

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