Axon regeneration of spinal motoneurons following a lesion at the cord-ventral root interface

Abstract

Those insults to the spinal cord which occur when ventral or dorsal roots are avulsed from the surface of the cord have been considered unfavourable with regard to both survival and axon regeneration of lesioned neurons. In this review, we describe the development of a surgical procedure aiming at a restoration of motor function after ventral root avulsion lesions. This development includes a series of investigations in animals, where an unexpected capacity for cell survival and axon regeneration of motoneurons after a cut lesion in the spinal cord was demonstrated and analyzed in great detail. Based on these ®ndings, a surgical technique was tested, where avulsed ventral roots were replanted into the cord. After con®rmation that such implanted roots could serve as a conduit for outgrowing motor axons in animals, the technique has been evaluated in a limited number of human cases of root avulsion lesions. We conclude that surgical intervention may indeed lead to return of motor function also in human cases of ventral root avulsion lesions. Interestingly, the procedure also seems to have an attenuating e ect on the pain that develops in cases with a combined dorsal root avulsion. Lastly, we conclude that the cut lesion in the ventral part of the spinal cord, followed by axon regeneration in motoneurons may serve as a model for axon regeneration in the central nervous system. Keywords: spinal cord; spinal cord injury; muscle reinnervation IntroductionThe type of nerve lesion that occurs when spinal nerve roots are torn o , avulsed, from the spinal cord surface, has in many respects been alikened traumatic lesions of the spinal cord itself. Thus, avulsion of ventral (mediating motor functions) or dorsal roots (meditating sensory functions) leads to the interruption of axons at the border between the central (CNS) and peripheral (PNS) nervous systems and in both cases a repair process requires axon growth within CNS tissue. From this reason, the prognosis for avulsion lesion victims has been regarded very unfavourable and considered not amenable to surgery. 1 Root avulsion lesions occur most frequently in spinal cord segments supplying nerve ®bres to the arm, particularly in conjunction with road tra c accidents or as a result of severe arm traction during complicated births. 2 It may also be seen in segments supplying the leg and in cases of injury to the cauda equina. Patients with these types of lesion su er from paralysis and sensory dysfunctions, sometimes including an extreme, almost unbearable pain. 1,3 The conventional approach to treat these injuries has been to apply non-curative, palliative methods, or to transfer intact neighbouring nerves to the distal stump of the avulsed root in attempts to compensate for the loss of sensimotor function. 4 Recently, however, a new surgical technique was introduced for treatment of avulsion lesions to ventral roots. 5 This method is based on results from a long series of animal experiments, where the regenerative capacity of motoneurons after lesions near the transitio...

Sialidase enhances spinal axon outgrowth in vivo

“…Avulsion occurs in Ͼ70% of brachial plexus injuries (7), and avulsion injury involving the ventral roots has a poor capacity for functional regeneration because of the physical separation of the axons and their nerve sheathes from their corresponding nerve cell bodies within the CNS (9). The mainstay of treatment is surgical and includes palliative surgery, such as nerve or muscle transfers, and restorative surgery, such as the implantation model used in this study (6,(10)(11)(12)(13). Two types of spinal cord implantation can restore connections between ventral horn neurons and their peripheral targets: reimplantation of the avulsed roots into the spinal cord and implantation of grafts between the spinal cord and distal nerve stumps or muscles.…”

“…Recently, implantation of avulsed spinal nerve roots or peripheral nerve grafts into the spinal cord to bridge the CNS to the peripheral nervous system has led to functional reconnection in patients, providing a method for restorative surgical treatments (6,11,12). Although these microsurgical techniques are promising treatments for brachial plexus avulsion injuries, functional improvement is limited (6,13).…”

The clinical study of repairing cauda equina fibres with fibrin glue after lumbar fracture and dislocation

“…Motor neurons in the anterior horn have more abundant blood supply than neurons of the dorsal ganglion that floats in a pool of cerebrospinal fluid of the subarachnoid space. Cullheim et al 17 noted that axon growth from a glial scar stopped at the borderline between the scar and the normal posterior fasciculus. Other reports also showed stoppage of growth at Clinical repair of cauda equina with fibre glue T Sun et al the dorsal root entry zone.…”

Reimplantation of avulsed lumbosacral ventral roots in the rat ameliorates injury-induced degeneration of primary afferent axon collaterals in the spinal dorsal columns

“…In addition, the ventral root implantation procedure introduces into the spinal cord the lesioned ventral root segment containing severed axons and their associated Schwann cells. However, Schwann cells do not appear to invade the spinal cord spontaneously following traumatic lesions to the ventral funiculus (Risling et al, 1983;Cullheim et al, 1999). It is possible that the implanted roots with associated Schwann cells may provide trophic support, as there is evidence that a peripheral nerve injury induces the proliferation of Schwann cells and increased production of brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), and nerve growth factor (NGF) (Salzer and Bunge, 1980;Meyer et al, 1992;Funakoshi et al, 1993;Naveilhan et al, 1997).…”