Restorative Neurology and Neuroscience - Volume 5, issue 1

Article Type: Other

DOI: 10.3233/RNN-1993-5101

Citation: Restorative Neurology and Neuroscience, vol. 5, no. 1, pp. vii-viii, 1993

Authors: Prochiantz, A. | Joliot, A. | Volovitch, M.

Article Type: Research Article

Abstract: It is a more and more widespread observation that growth factors can, on occasion, be found within nuclei where they may serve as trans-activating factors. This dual action raises the possibility that, on their side, trans-activating factors might be secreted and act both at the membrane and at the nuclear level of target cells. At the same time it has now been clearly demonstrated that the classical growth factors bFGF and TGF-b are good in vitro mesodermal inducers and may have in vivo counterparts. Neural inducers, unfortunately, remain much more elusive even though the phenomenon of neural induction was described …almost 60 years ago. Here, we present a short review on the development of the nervous system in which we focus on the importance of homeobox proteins in inductive phenomena. We follow on to propose that some trans-activating factors belonging to the homeoprotein family may have paracrine and autocrine functions and might thus participate directly in neural induction. This highly hypothetical proposal is based on evidence from the literature and on experiments carried out in our laboratory showing that the antennapedia homeobox peptide (pAntp) added to neurons in culture is internalised by these cells, conveyed to their nuclei and provokes their morphological differentiation. Show more

DOI: 10.3233/RNN-1993-5102

Citation: Restorative Neurology and Neuroscience, vol. 5, no. 1, pp. 3-7, 1993

Authors: Fitzgerald, Maria

Article Type: Research Article

DOI: 10.3233/RNN-1993-5103

Citation: Restorative Neurology and Neuroscience, vol. 5, no. 1, pp. 8-9, 1993

Authors: Krumlauf, Robb | Hunt, Paul | Sham, Mai Har | Whiting, Jenny | Nonchev, Stefan | Marshall, Heather | Graham, Anthony | Papalopulu, Nancy | Cook, Martyn | Boncinelli, Edoardo | Wilkinson, David

Article Type: Research Article

DOI: 10.3233/RNN-1993-5104

Citation: Restorative Neurology and Neuroscience, vol. 5, no. 1, pp. 10-12, 1993

Authors: Henderson, Christopher E. | Bloch-Gallego, Evelyne | Camu, William | Gouin, Annie | Mettling, Clément

Article Type: Research Article

Abstract: Factors affecting neuronal growth may be considered to fall into two major categories: those required for neuronal survival during development or following a lesion, and those which enhance growth or regeneration of axonal or dendritic processes. We briefly review here some recent studies on the former in spinal cord development and plasticity as an introduction to other papers in the session on Factors controlling Neural Growth, and then present in more detail work on factors affecting motoneuron development in vitro. The neurotrophins are a closely-related family of basic neurotrophic factors including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) …and neurotrophins -3, -4 and -5 that enhance neuronal survival by binding to surface receptors whose major components are the trk tyrosine kinases and p75NGF-R . Only the latter has been studied in the context of spinal cord neuroplasticity: its levels on motoneurons are up-regulated following central or peripheral trauma, although its function there remains unknown. Much evidence exists for the existence of ‘motoneuron growth factors’ involved in regulation of survival and development of spinal motoneurons. Following a critical comparison of techniques for their purification, we review results obtained in vitro and in vivo using known growth factors such as ciliary neurotrophic factor (CNTF), basic fibroblast growth factor (bFGF) and transforming growth factor (TGF/β1). Although none of them satisfies all the criteria for the embryonic ‘motoneuron growth factor’, CNTF is of potential interest for reducing motoneuron loss in pathological situations. Show more

Keywords: Motoneuron, Neuronal growth factor, Neurotrophin, Denervation, SCI antibody

DOI: 10.3233/RNN-1993-5105

Citation: Restorative Neurology and Neuroscience, vol. 5, no. 1, pp. 15-28, 1993

Authors: Barde, Y.A.

Article Type: Research Article

DOI: 10.3233/RNN-1993-5106

Citation: Restorative Neurology and Neuroscience, vol. 5, no. 1, pp. 29-29, 1993

Authors: Ibáñez, Carlos F. | Persson, Håkan

Article Type: Research Article

DOI: 10.3233/RNN-1993-5107

Citation: Restorative Neurology and Neuroscience, vol. 5, no. 1, pp. 30-31, 1993

Authors: Schnell, Lisa | Schwab, Martin E.

Article Type: Research Article

DOI: 10.3233/RNN-1993-5108

Citation: Restorative Neurology and Neuroscience, vol. 5, no. 1, pp. 32-33, 1993

Authors: Murray, Marion

Article Type: Research Article

Abstract: There is considerable evidence supporting a naturally occuring increase in the density of projections by intact systems induced by partial denervation of targets within the spinal cord. The phenomenon of sprouting in the spinal cord appears to be quite similar to the denervation evoked sprouting shown elsewhere in the CNS. Sprouting appears to be regulated rather than random since not all systems projecting to a denervated region may show demonstrable sprouting. In adults, the extent of sprouting is usually limited to the normal target zone of the intact systems and thus reasonably rigorous quantitative methods may be required to provide …a clear demonstration of the increased projection. Greater plasticity, including regenerative like changes can be elicited in the undamaged processes of DRGs within the CNS by lesion to the peripheral process. Expansion of terminal fields into novel territories in adults has been demonstrated most convincingly in cases where additional manipulations are made, e.g. addition of peripheral nerve injury to the lesion paradigm. This suggests that the limitation on sprouting in adults can be overridden by increasing the metabolic drive of the sprouting neurons. In contrast there appear to be fewer limitations on sprouting in the neonate, since extensive sprouting into aberrant targets occurs if denervation occurs before development has ceased. Changing patterns of synaptic activity can also evoke quite dramatic modifications of the synthetic activity of neurons. Some of these changes appear to be long lasting and may lead to modifications in the activity of spinal neurons. Naturally occurring plasticity thus represents a major compensatory response to CNS lesions which needs to be taken into account in considering the consequences of CNS lesions, the extent of recovery of function and ways of improving the extent of recovery of function. Show more

DOI: 10.3233/RNN-1993-5109

Citation: Restorative Neurology and Neuroscience, vol. 5, no. 1, pp. 37-45, 1993

Authors: Nothias, Fatiha | Tessler, Alan | Murray, Marion

Article Type: Research Article

DOI: 10.3233/RNN-1993-5110

Citation: Restorative Neurology and Neuroscience, vol. 5, no. 1, pp. 46-47, 1993

Authors: Moonen, G. | Delree, P. | Martin, D. | Sadzot-Delvaux, C. | Schoenen, J.

Article Type: Research Article

DOI: 10.3233/RNN-1993-5111

Citation: Restorative Neurology and Neuroscience, vol. 5, no. 1, pp. 48-48, 1993

Authors: De Felipe, Carmen | Jenkins, Robert | O'Shea, Ross | Williams, Simon | Hunt, Stephen

Article Type: Research Article

DOI: 10.3233/RNN-1993-5112

Citation: Restorative Neurology and Neuroscience, vol. 5, no. 1, pp. 49-50, 1993

Authors: Woolf, Clifford J.

Article Type: Research Article

DOI: 10.3233/RNN-1993-5113

Citation: Restorative Neurology and Neuroscience, vol. 5, no. 1, pp. 51-52, 1993

Authors: Lombard, M.C. | Besse, D. | Besson, J.M.

Article Type: Research Article

DOI: 10.3233/RNN-1993-5114

Citation: Restorative Neurology and Neuroscience, vol. 5, no. 1, pp. 53-55, 1993

Authors: Kreutzberg, Georg W.

Article Type: Research Article

Abstract: Axonally injured neurons demonstrate profound changes in morphology, in metabolism and in housekeeping functions. Specifically, changes in cytoskeletal proteins, in neurotransmitter metabolism, in growth and maintenance factors seem to be correlated to the growth of the new axons as part of the regeneration program. Significant changes have been described in the perineuronal glial cells of a motor nucleus undergoing retrograde axonal reaction, the so-called chromatolysis. Microglia become activated, augmented, mobile and instrumental in the synaptic stripping process. Astrocytes become first hypertrophic and, in a delayed reaction, form insulating lamellae around the recovering neurons. The molecular signals that could mediate the …accompanying glial reactions are presumed to be produced by the injured neurons. Cytokines, but also neuropeptides and nitric oxide, are likely candidates. Show more

Keywords: Motoneuron regeneration, Growth factor receptor, NO synthase, CGRP, Intercellular signal

DOI: 10.3233/RNN-1993-5115

Citation: Restorative Neurology and Neuroscience, vol. 5, no. 1, pp. 59-60, 1993

Authors: Cadusseau, J. | Nothias, F. | Alanbari, A. | Peschanski, M.

Article Type: Research Article

DOI: 10.3233/RNN-1993-5116

Citation: Restorative Neurology and Neuroscience, vol. 5, no. 1, pp. 61-63, 1993

Authors: Tessler, A. | Goldberger, M.E. | Himes, B.T. | Howland, D.R. | Itoh, Y. | Pinter, M.J.

Article Type: Research Article

DOI: 10.3233/RNN-1993-5117

Citation: Restorative Neurology and Neuroscience, vol. 5, no. 1, pp. 64-65, 1993

Authors: Goldberger, Michael | Murray, Marion | Tessler, Alan

Article Type: Research Article

Abstract: Plasticity of undamaged projections (axonal sprouting) in the adult and neonatal mammalian spinal cord has been documented many times. It has been associated, in some paradigms, with recovery of specific functions and motor behavior. This mutually occurring recovery of function appears to be enhanced by transplants of fetal tissue.

DOI: 10.3233/RNN-1993-5118

Citation: Restorative Neurology and Neuroscience, vol. 5, no. 1, pp. 69-75, 1993

Authors: Bresnahan, Jacqueline C. | Behrmann, Donald L. | Beattie, Michael S.

Article Type: Research Article

DOI: 10.3233/RNN-1993-5119

Citation: Restorative Neurology and Neuroscience, vol. 5, no. 1, pp. 76-76, 1993

Authors: Beattie, Michael S. | Bresnahan, Jacqueline C. | Leedy, M. Gail

Article Type: Research Article

DOI: 10.3233/RNN-1993-5120

Citation: Restorative Neurology and Neuroscience, vol. 5, no. 1, pp. 77-78, 1993

Authors: Kruse, M.N. | de Groat, W.C.

Article Type: Research Article

DOI: 10.3233/RNN-1993-5121

Citation: Restorative Neurology and Neuroscience, vol. 5, no. 1, pp. 79-80, 1993

Authors: Barbeau, Hugues | Danakas, Michel | Arsenault, Bertrand

Article Type: Research Article

DOI: 10.3233/RNN-1993-5122

Citation: Restorative Neurology and Neuroscience, vol. 5, no. 1, pp. 81-84, 1993

Authors: Peschanski, Marc | Le Forestier, Nadine | Rapisardi, Salvatore

Article Type: Research Article

Abstract: The concept of neuroplasticity in the adult is now well accepted. Amongst the most striking neuroplastic phenomena are those that systematically follow a lesion in the neural system itself. The work reported in this symposium emphatically illustrates the plasticity of neurons participating in spinal cord networks in various conditions that involve axonal lesions and neuronal degeneration. The purpose of this paper is to evaluate the potential for post-lesion neuroplastic changes to serve as a basis for future therapeutics with specific emphasis on two important pathologies observed in humans: spinal cord injuries and degenerative motoneuronal diseases. Spontaneous attempts at axonal regeneration …and growth of axotomized neurons can be seen after a spinal trauma although the number of neurons involved is often low and variable from one population to another. In any case, axons fail to cross the scar tissue, most probably due to specific neurono-glial interactions. Successful recovery of neural systems (and therefore possible functional recovery) that can be expected as a result of these spontaneous attempts at regeneration of axotomized axons is, overall, very poor. Innumerable attempts have been made to provide severed axons in the spinal cord with a suitable substrate. Altogether, the results obtained when regeneration is facilitated in the adult through a series of different ways point to several remarkable conclusions: (i) adult neurons are indeed able to grow an axon; (ii) the failure to grow an axon after axotomy which is normally observed depends, at least in part, on an unsuitable substrate; (iii) growth ability seems to be much more restricted for neurons with large myelinated axons than for neurons with unmyelinated ones. Several therapeutic avenues can be considered that can be grouped in three different endeavors: to fill in the gap, and to change the nature of the gap, to protect fibers that have not been directly injured. An additional possibility is that compensation of lost inputs by transplants of monoaminergic neurons below the level of the lesion can be of therapeutic value. Experimental models of spinal neurodegeneration have been less intensely studied than those of spinal cord injuries. Data suggesting the existence of spontaneous neuronal plasticity in the aftermath of motoneuronal loss are, however, available. Two types of neuronal attempts at regeneration can be considered: sprouting of surviving motoneurons leading to the reoccupation of vacant motor endplates and possible attempts to grow by afferents that have been deprived of their postsynaptic target cells. These attempts may be facilitated experimentally by the use of growth factors and fetal neural transplants. The use of growth factors may be of therapeutic value and preliminary studies are presently in progress. The therapeutic value of neural transplants to replace lost motoneurons in amyotrophic lateral sclerosis or spinal muscular atrophies is not easily determined. It seems excluded that transplanted motoneurons replace lost neurons at all levels of the neuraxis. In contrast, neural transplantation may be interesting to replace a specific set of motoneurons, namely those controlling respiratory muscles. Show more

DOI: 10.3233/RNN-1993-5123

Citation: Restorative Neurology and Neuroscience, vol. 5, no. 1, pp. 87-97, 1993

Article Type: Research Article

DOI: 10.3233/RNN-1993-5124

Citation: Restorative Neurology and Neuroscience, vol. 5, no. 1, pp. 99-101, 1993