Restorative Neurology and Neuroscience - Volume 1, issue 1

Authors: Seil, Fredrick J.

Article Type: Review Article

Abstract: Exposure of cerebellar cultures derived from neonatal mice to cytosine arabinoside for the first 5 days in vitro results in destruction of cerebellar granule cells and inhibition of glial maturation. Such cultures undergo reorganizational changes, primary features of which are a sprouting of Purkinje cell recurrent axon collaterals and the formation of recurrent axon collateral-Purkinje cell dendritic spine synapses. Such heterotypical synapses are inhibitory, in contrast to the excitatory parallel fiber-Purkinje cell dendritic spine synapses normally present. If locus coeruleus neurons are included with the cerebellar cultures, the catecholaminergic axons also sprout, and tissue levels of catecholamines are increased. Purkinje …cell survival is enhanced in Ara C-treated cultures, as the target field for Purkinje cell axonal projections is expanded. Oligodendrocyte inhibition results in failure of myelination, and astrocyte inhibition, when it occurs, is associated with a failure of Purkinje cell ensheathment and a hypennnervation of Purkinje cell somata by sprouted recurrent axon collateral terminals. Transplantation of such cultures with granule cells and glia reverses many of these changes. Parallel fiber-Purkinje cell dendritic spine synapses are formed, and most heterotypical synapses disappear. The Purkinje cell population is reduced to normal, and most of the sprouted recurrent axon collaterals are eliminated. However, sprouted catecholaminergic axons are not significantly reduced. Transplanted cultures become myelinated and Purkinje cells acquire astrocytic sheaths, with an associated reduction of axosomatic synapses. Transplantation with glia alone does not reduce the sprouted recurrent axon collaterals, but does result in astrocytic ensheathment of Purkinje cells and an associated decrease of axosomatic synapses. These tissue culture models illustrate some of the plastic changes that the nervous system may undergo following injury and transplantation. Show more

Keywords: Axonal sprouting, Catecholamine, Cerebellar culture, Cytosine arabinoside, Glial inhibition, Heterotypical synapse, Neural plasticity, Transplantation

DOI: 10.3233/RNN-1989-1101

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 1, pp. 1-11, 1989

Authors: Castro, A.J. | Sørensen, J.C. | Tønder, N. | Bold, L. | Zimmer, J.

Article Type: Research Article

Abstract: Several reports have demonstrated efferent projections from fetal neocortical transplants placed in the cerebral cortex of newborn rats. Fewer studies have examined transplant afferents, and these have primarily used techniques based on the axonal transport of horseradish peroxidase. In the present study, we extend these initial findings on transplant afferent connections by using retrogradely transported fluorescent dyes to demonstrate a topographic and more extensive pattern of cortical transplant afferents than has been previously reported. Fetal neocortical tissue was grafted into frontal cortical lesion cavities made by aspiration in newborn rats. At 1.5–10 months later, the fluorescent dyes Fast blue and …Diamidino yellow were injected into the transplants. Subsequent histological analysis demonstrated numerous retrogradely labeled fluorescent neurons within the host thalamus and cerebral cortex as well as several other areas of the host brain. The neurons were primarily single-labeled and generally found in areas that normally project to the ablated area of the cortex. The topographic distribution of retrograde labeling in several animals with non-overlapping dye injections confined to the transplants suggests that the host projections were distributed selectively within the grafts. These results support and extend previous studies suggesting the use of fetal neocortical tissue in repair of the neonatally damaged central nervous system. Show more

Keywords: Neuronal transplantation, Neocortex, Newborn, Thalamus

DOI: 10.3233/RNN-1989-1102

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 1, pp. 13-23, 1989

Authors: Bisby, M.A. | Redshaw, J.D. | Tetzlaff, W. | de Leon, M. | Carlsen, R.C.

Article Type: Research Article

Abstract: Labelled proteins conveyed by fast axonal transport into the sensory axons of frog sciatic nerve following axotomy have been studied by 2D gel electrophoresis. Previous work showed that in frogs acclimatized to 25 °C a cell body reaction occurs, along with regeneration of axons to their targets. In contrast, frogs acclimatized to 15 °C showed no cell body reaction and though regeneration began, it stalled after approximately 35 days. We found that axotomy at 25 °C was followed by an increase in transport of specific labelled proteins corresponding to growth-associated proteins (GAPs) identified in other regenerating systems. Surprisingly, axotomy at …15 °C also induced a similar increase, though with a slower onset, so that the highest levels of expression of GAPs occurred during the time when the axons had stalled. We conclude that sensory neurons in 15 °C frogs do detect that their axons have been injured, as shown by their ability to increase GAP synthesis. Slow and limited axonal growth is possible during a period when GAP synthesis is low compared to levels in rapidly regenerating nerves, but even when the ability to produce GAPs increases, this alone is not sufficient to sustain regeneration in the absence of other components of the cell body reaction to injury. Show more

Keywords: Growth-associated protein, Regeneration, Cold-acclimatization, Cell body reaction, Axonal transport, Frog sciatic nerve

DOI: 10.3233/RNN-1989-1103

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 1, pp. 25-29, 1989

Authors: Rosario, Carlos M. | Fry, Keith R. | Madison, Roger

Article Type: Research Article

Abstract: The major objective of the experiments reported in this paper was to qualitatively test the hypothesis that rabbit retinal ganglion cells survive optic nerve transection and entubulation repair of the proximal optic nerve stump. The optic nerve of rabbits was transected immediately behind the globe, and a 1-cm length of a Type I collagen nerve guide tube was sutured onto the short proximal stump. The nerve guide was either left empty or was filled with a Type I collagen gel (Vitrogen, Collagen Corp.). Following 8–12 weeks survival time, the animals were sacrificed and the retinae were prepared as whole mounts …and processed for immunocytochemistry using an antibody which selectively labels the retinal ganglion cells. Although no formal cell counts were carried out, the animals which received Vitrogen within the nerve guide showed a qualitative enhancement of retinal ganglion cell survival compared to the group with the nerve guide alone. The results suggest that specific manipulations of the central nervous system microenvironment may enhance neuronal survival following axonal transection. Show more

Keywords: Entubulation repair, Central nervous system, Collagen, Monoclonal antibody, Rabbit

DOI: 10.3233/RNN-1989-1104

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 1, pp. 31-37, 1989

Authors: Hsueh, I.-H. | Toyoshima, E. | Mayer, R.F.

Article Type: Research Article

Abstract: In order to test whether 4-aminopyridine (4-AP), a potassium channel blocker, may be of therapeutic value in demyelinating neuropathies, a focal tibial nerve conduction block with demyelination was produced in adult rats by an intraneural microinjection of potassium tellurite. Onset and recovery of the lesion were monitored by evoked compound muscle action potentials (CMAP) activated from the proximal and distal nerve one day before and 1, 4, 7, 14, 21 and 28 days after the injection. Intraperitoneal 4-AP (2 mg/kg) or buffered saline were injected prior to the potassium tellurite and 6 days per week for 28 days. The data …show that 4-AP is tolerated, it does not prevent conduction block, and only has a modest effect on increasing its recovery from day 4 to 7 (91 % increase in CMAP ratio compared with control of 35%). Recovery is similar by day 28 in 4-AP treated or untreated animals. These results suggest that 4-AP will have limited use in the therapy of subacute demyelinating neuropathies. Show more

Keywords: Tellurium neuropathy, Nerve conduction block, Paranodal demyelination, 4-Aminopyridine, Potassium channel

DOI: 10.3233/RNN-1989-1105

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 1, pp. 39-46, 1989

Authors: Pommerenke, Klaus | Markowitsch, Hans J.

Article Type: Research Article

Abstract: Training-dependent improvement of visual behavior after postgeniculate damage of the visual system was studied in 10 patients. The patients, all with computer-tomographically proven damage and a lesion chronicity of 8 weeks to 4.7 years, were subjected to a special exploration training of at least 10 sessions or 1100 trials. Before and after training, extensive perimetric tests were performed to determine possible training-related visual changes. It was found that the training program improved visual exploration considerably and induced qualitative shifts in exploration strategy even for patients who had failed to adopt these strategies for more than 3 years postlesion. On the …other hand, a training-based visual field enlargement was not supported when applying strict criteria. It is concluded that specific and systematic exploration training can be of significant help for improving visuo-spatial behavior in hemianopic patients, but that a reliable visual field enlargement is unlikely to occur in unselected patients trained and examined under standard conditions. Show more

Keywords: Hemianopia, Exploration training, Visual field defect, Searching field, Searching strategy, Visual field border

DOI: 10.3233/RNN-1989-1106

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 1, pp. 47-63, 1989

Authors: De Leon, Marino | Carlsen, Richard C.

Article Type: Research Article

Abstract: Peripheral nerve regeneration requires a reorganization of neuronal synthesis and axonal transport to replace the degenerating axon. This study examines the time course, the extent and the molecular components which comprise the observed increases in protein fucosylation and fast axonal transport of fucosylated proteins in regenerating frog peripheral nerves. The in vitro spinal ganglia-sciatic nerve preparation used in these experiments allowed comparisons to be made between axotomized and intact neurons from the same animal, incubated in the same [3 H]fucose-containing solution, and subjected to the same axonal transport conditions. Thus, we were able to show that the fucosylation of constituent …proteins increased in axotomized neurons without an increase in the membrane transport of fucose or neuronal protein synthesis. An increase in the amount of newly fucosylated protein conveyed by fast transport preceded the apparent increase in neuronal synthesis by approximately 3 days. The increase in anterograde transport was initiated just subsequent to a transient increase in retrograde or ‘turnaround’ transport, suggesting a possible association between the two responses. The protein (distinguished on the basis of molecular weight) undergoing the most pronounced increase in fucosylation in the cell body was different from that in the nerve, but there was no evidence for the production of novel glycoproteins. The data indicate that protein fucosylation increases significantly in regenerating neurons and that an increase in the incorporation of newly fucosylated protein into the fast axonal transport system precedes an increase in synthesis. The increase in transport of fucosylated protein may be one of the earliest responses directed toward the generation of a new axon. Show more

Keywords: Nerve regeneration, Glycoprotein, Axonal transport, Frog, Fucose, Condition, Test lesion

DOI: 10.3233/RNN-1989-1107

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 1, pp. 65-75, 1989

Authors: Verma, S. | Kumar, V. Mohan | Gopinath, G. | Sharma, R. | Tandon, P.N.

Article Type: Research Article

Abstract: Kainic acid lesion of the medial preoptic area resulted in the impairment of the thermoregulation and disruption of the reproductive cycle in female rats. The preoptic–anterior hypothalamic area from fetal donor was transplanted into the lesioned area ofthe host. After transplantation, these animals showed signs of estrus cyclicity and a recovery in basal temperature towards normal. They also showed a reduced shift of body temperature on exposure to a hot environment. Thus the female rats, which received transplantation, showed some degree of recovery of functions which were disrupted by kainic acid lesions.

Keywords: Preoptic-anterior hypothalamic area, Kainic acid, Female reproduction, Thermoregulation, Transplantation

DOI: 10.3233/RNN-1989-1108

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 1, pp. 77-81, 1989

Authors: Dunnett, S.B. | Martel, F.L. | Rogers, D.C. | Finger, S.

Article Type: Research Article

Abstract: Wound-derived trophic factors released by the injured brain are thought to reach a peak 1–2 weeks after injury. It has been proposed that such factors can promote the survival, growth and functional capacity of embryonic tissue grafts. To test the generality of this hypothesis, control rats and rats with aspirative fimbria-fornix lesions were compared with 5 groups of rats with lesions and septal grafts implanted either in the same session as the lesion or after delays from 10 days to 9 months. Animals were assessed 3 months post-transplantation on an operant differential reinforcement of low rates (DRL) task and on …a test of spontaneous locomotor activity. Lesions produced impairments on all measures of DRL performance. Two graft groups showed amelioration of the DRL deficits, one graft group was unchanged, and the deficits were exacerbated in two others. There was no clear relationship between lesion–graft interval and recovery. An inverse relationship was seen, however, between recovery and the developmental age of the donor tissue. In contrast, significant recovery from lesion-induced hyperactivity was observed in the two graft groups with tissue derived from the oldest embryos. There were no clear relationships between recovery on either test, lesion–graft interval, and AChE-positive reinnervation of the host brain. The results provide further evidence that septal grafts can reverse behavioural deficits induced by fimbria-fornix lesions under some conditions, but suggest that the timing of graft surgery may not be as important a factor as donor age in this model system. Show more

Keywords: Septal graft, Hippocampus, Cholinergic system, Differential reinforcement of low rates (DRL), Activity, Trophic factor

DOI: 10.3233/RNN-1989-1109

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 1, pp. 83-92, 1989

Article Type: Research Article

DOI: 10.3233/RNN-1989-1110

Citation: Restorative Neurology and Neuroscience, vol. 1, no. 1, pp. 95-100, 1989