Hypotheses Concerned With Axonal Regeneration in the Mammalian Nervous System

Kiernan, J. A.

doi:10.1111/j.1469-185x.1979.tb00871.x

Cited by 258 publications

(72 citation statements)

References 204 publications

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“…It is assumed now that central nerve regeneration is functionally possible but that it is limited as a result of extrinsic factors. Since dif fusible factors are very likely to circulate within the blood system, we have tested, in the present study, the type of humoral changes occurring follow ing the spinal cord injury and which might exert some effect on the sub sequent capability to recover as has been speculated recently (Kiernan, 1979)· We have found that antibodies against several myelin antigenic deter minants are produced in the spinal cord injured patients which remain in the sera for years following the injury. Production of antibodies against autoantigens have been found in other patients experiencing neuronal dis orders of varous types (Caspary and Chambers, 1970;Cook and Dowling, 198 I;Aviel et al, in press) as well as in experimental peripheral nerve injury in animals .…”

Section: Discussionmentioning

confidence: 95%

Systemic humoral factors participating in the course of spinal cord injury

et al. 1983

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Summary. Systemic humoral factors have been studied in traumatic, chronic and acute spinal cord injured patients. Antibodies specific to nervous system auto antigens were detected in a majority of the sera obtained from these patients, at different periods after injury. Limited in vitro sprouting of dorsal root ganglia in chicken embryos was observed in the presence of serum from these patients. The possible association between growth inhibiting factors and the presence of antibodies against nervous tissue autoantigens is discussed.

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Section: Discussionmentioning

confidence: 95%

Systemic humoral factors participating in the course of spinal cord injury

et al. 1983

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“…17 Thus, such a defect could be demonstrated still at 2 years after the induction of the lesion, while substantially shorter defects in blood ± brain barrier function (4 ± 6 weeks) have been reported in other types of CNS lesions. 18,19 The implication of this ®nding for the regenerative capacity is unknown, but it is of interest that in scars with short-lasting barrier dysfunction, there is a transient presence of numerous axon sprouts in the scar for a time period that is equivalent with that of the barrier defect. One possible reason for the lively regenerative activity in our lesion model could then be that blood-borne substances that stimulate nerve growth and that are normally excluded from the nervous tissue, are in fact¯ooding into the scar area.…”

Section: Introductionmentioning

confidence: 99%

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

1999

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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...

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“…In the absence of experimental intervention, olfactory axons are usually successful at reinnervating the olfactory bulb (Graziadei and Monti Graziadei, 1978;Monti Graziadei and Graziadei, 1979;Barber, 1982a;Doucette et al, 1983;Doucette, 1990), but the regenerative effort of most other types of axons within the CNS fails to support more than a minimal amount of growth (Kiernan, 1979;Reier et al, 1989;Fawcett, 1998). This dichotomy in the success of axonal growth appears due, at least in part, to the different glial cell environments through which olfactory and nonolfactory axons must grow (Doucette, 1990(Doucette, , 1995Ramon-Cueto and Valverde, 1995;Franklin and Barnett, 1997;Fawcett, 1998;.…”

Section: Are Oecs a Clinically Relevant Alternative To Schwann Cells?mentioning

confidence: 99%

“…In contrast, axons regenerating within the peripheral nervous system (PNS) are often successful in reinnervating sensory and effector organs so that almost normal function is restored (Kiernan, 1979;Baher and Bonhoeffer, 1994;Brecknell and Fawcett, 1996;Fawcett, 1998;Fawcett and Asher, 1999;Fraher, 1999;Behar et al, 2000). Both oligodendrocytes and astrocytes undoubtedly play a major role in this abortive regeneration of CNS axons due to the presence of inhibitory molecules as well as to the lack of sufficient growth promoting molecules (Reier and Houle, 1988;Hoke and Silver, 1994;Moore and Thanos, 1996;Gebicke-Haerter et al, 1996;Frisen, 1997;Ridet et al, 1997).…”

Section: Introductionmentioning

confidence: 99%