Restorative Neurology and Neuroscience - Volume 4, issue 2

Authors: Cassel, J.C. | Kelche, C. | Majchrzak, M. | Will, B.E.

Article Type: Research Article

Abstract: After twenty years of intensive research, the possibility to induce recovery from various disorders in brain damaged mammals by means of intracerebral grafts of fetal CNS tissue is well documented and largely accepted by the scientific community. However, there are several reports on animal research suggesting that intracerebral grafts may fail to induce the expected recovery after brain injury or even that they may cause deficits which are actually more pronounced than those induced by the lesions alone. In addition, attempts to produce functional benefits with catecholamine-releasing tissue grafts in the brain of Parkinsonian patients have given limited and variable …results; graft-induced deleterious effects have also been occasionally reported in a few clinical cases. One way to progress towards a better understanding of such disappointing, although informative, discrepancies between successful and less successful experimental studies and clinical trials would be to consider that there are several factors which may influence, in one direction or the other, the survival, development, integration and functional expression of intracerebral fetal CNS grafts. The present review considers the following factors: (i) some of the technical factors such as the constraints of transplantation surgery, the origin of donor tissue, the implantation site, the age of both the donor and the recipient, and tissue manipulations prior to grafting (i.e., cryopreservation, culture, genetic modification); (ii) exogenous and endogenous neurotrophic factors, the latter being distinguished by whether they may be host- or graft-derived; (iii) immunological factors (from the particular immunological status of the brain to some effects of immunosuppression in the case of xenografting)’, (iv) pharmacological factors, with a particular focus on experimental data suggesting that administration of drugs may or might contribute to elicit, enhance or block some functional effects of grafts. It is concluded that all these factors may become simultaneously operative and interacting, thereby presiding over the functional outcome of intracerebral grafting in both experimental research and clinical trials. Show more

Keywords: Functional recovery, Immunology, Intracerebral transplantation, Lesion, Neurotrophic factors, Pharmacology, Techniques

DOI: 10.3233/RNN-1992-4201

Citation: Restorative Neurology and Neuroscience, vol. 4, no. 2, pp. 65-96, 1992

Authors: Murray, Marion | Sharma, Sansar C.

Article Type: Research Article

Abstract: The nature of the expansion of the visual field projection was studied in goldfish in which size disparities were created between the retina and the tectum. After removal of one-half of the retina, the remaining retinal ganglion cells expand their projections so that the entire contralateral optic tectum is encompassed (Schmidt et al.1978). We wished to determine whether this expansion is accompanied by increased arborization including proliferation of synaptic terminals by the spared retinal ganglion axons or whether field expansion is accomplished by increased arborization without changes in synaptic number. Portions of the retina were ablated and the animals were …allowed to survive for at least 5 months, the time at which expansion can be demonstrated, before sacrifice. We mapped retinotectal projections to determine the extent of the expanded visual fields and used stereological and morphometric analyses of synaptic contacts in the retinal target lamina, the stratum fibrosum et griseum superficialis (SFGS), in the optic tectum to estimate synaptic number. Numbers of synaptic terminals in the SFGS contralateral to the lesioned retina were not different from numbers in the comparable portion of control tecta. These observations indicate that the surviving retinal axons increased the number of synaptic contacts on tectal target cells in response to removal of other retinal ganglion cells. Show more

Keywords: Goldfish, Retinotectal system, Synaptic plasticity, Half-retinal preparation

DOI: 10.3233/RNN-1992-4202

Citation: Restorative Neurology and Neuroscience, vol. 4, no. 2, pp. 97-105, 1992

Authors: Raivich, G. | Dumoulin, F.L. | Streit, W.J. | Kreutzberg, G.W.

Article Type: Research Article

Abstract: Calcitonin-gene related peptide (CGRP) is a neuromodulatory peptide present in motoneurons and a subpopulation of sensory neurons of the adult peripheral nervous system. Here we have investigated the changes in axonal transport of CGRP and CGRP receptor expression in the injured and regenerating rat sciatic nerve using CGRP-immunocytochemistry, radioimmunoassay and quantitative in situ receptor autoradiography techniques. Axotomy led to a gradual and prolonged, 2.5- to 3.5-fold increase in specific CGRP binding to the distal part of the crushed sciatic nerve, beginning 4–6 days after axotomy. An even stronger, up to 30-fold increase was observed after 30–42 day denervation in the …distal part of the transected sciatic nerve, where neurite reinnervation was prevented by retroversion and ligation of the proximal nerve stump. Reconnection of the proximal and distal nerve stumps 21 days after transection did not lead to a major reduction in specific CGRP binding but prevented a further increase that occurred between 21 and 42 days after transection without reconnection. In contrast, the anterograde axonal transport of CGRP decreased after axotomy to 40–50% of the control values 6–8 days after nerve crush but recovered towards normal levels during successful regeneration. Interestingly, the retrograde axonal transport of CGRP appeared to amount to only 10–20% of the anterograde transport, suggesting that the peptide may be released by the regenerating neurites into the endoneurium of the injured peripheral nerve. In view of the persistent upregulation in endoneural CGRP binding after axotomy these data indicate that axonal CGRP could play a regulatory role in mediating axonal–endoneural cell interaction during peripheral nerve regeneration. Show more

Keywords: Peripheral nerve injury, Neuropeptide: Axonal transport, CGRP-receptor expression, Neurite outgrowth

DOI: 10.3233/RNN-1992-4203

Citation: Restorative Neurology and Neuroscience, vol. 4, no. 2, pp. 107-115, 1992

Article Type: Research Article

DOI: 10.3233/RNN-1992-4204

Citation: Restorative Neurology and Neuroscience, vol. 4, no. 2, pp. 117-125, 1992