Restorative Neurology and Neuroscience - Volume 11, issue 1-2

Authors: Hoffman, Stuart W. | Stein, Donald G.

Article Type: Research Article

Abstract: Male rats received bilateral frontal cortex contusions and were injected with 100 mg/kg of EGb 761 or an equal volume of vehicle beginning 5 min after injury and then with 1 injection/day for 7 days. The rats were tested for spontaneous motor behavior on days 1, 5, 10, and 15 postinjury and then for 10 days of spatial navigation performance in the Morris Water Maze (MWM), beginning on the day 8 after the contusion. Brain tissue was removed for examination on the 18th day after injury. Contused rats given EGb 761 performed more like intact rats on measures of spontaneous …motor activity while vehicle-treated counterparts remained more active than either shams or EGb 761-treated animals by the conclusion of testing. Contusion-only rats were worse than shams on spatial performance, while those given EGb 761 were less impaired. Histological analyses indicated that EGb 761 failed to prevent loss of tissue at the primary site of impact. However, the extract reduced retrograde degeneration of neurons, gliosis in the thalamus, and ex vacuo hydrocephalus. EGb 761 treatment also decreased the loss of ChAT-positive neurons in the dorsomedial caudate-putamen and in the nucleus basalis magnocellularis (NBM). The results of this study indicate that EGb 761 could be a possible treatment for traumatic brain injury. Show more

Keywords: Traumatic brain injury, Free radical scavenger, Platelet activating factor antagonist, Cognitive performance, Spontaneous motor behavior, Gliosis, Neuronal sparing

DOI: 10.3233/RNN-1997-111201

Citation: Restorative Neurology and Neuroscience, vol. 11, no. 1-2, pp. 1-12, 1997

Authors: Johnston, Rowena E. | Hu, Xiu-Ti | White, Francis J. | Becker, Jill B.

Article Type: Research Article

Abstract: Grafts of fetal ventral mesencephalic (VM) tissue into the striatum of unilaterally 6-hydroxydopamine lesioned rats reduce many of the behavioural and neural changes associated with the lesion. In this report, the ability of such grafts to restore the qualitative and quantitative synergistic relationship between Dl-like and D2-like receptors in the striatum was investigated. In animals with a unilateral 6-hydroxydopamine lesion of the nigrostriatal bundle, there was a loss of qualitative and quantitative DA receptor coupling in the striatum, consistent with previous reports. Intrastriatal fetal VM grafts restored both qualitative and quantitative DA receptor synergism to the same level as was …observed in the intact striatum. Thus, the ability of intrastriatal grafts to ameliorate some behavioural deficits observed after unilateral lesion may be due to the recoupling of DA D1/D2 synergisms within the striatum. Show more

Keywords: Fetal transplants, Striatum, Dl dopamine receptors, D2 dopamine receptors, Extracellular recording, 6-hydroxydopamine, Parkinson's disease

DOI: 10.3233/RNN-1997-111202

Citation: Restorative Neurology and Neuroscience, vol. 11, no. 1-2, pp. 13-20, 1997

Authors: Lindner, Mark D. | Plone, Melissa A. | Frydel, Beata | Kaplan, Faith A. | Krueger, Paula M. | Bell, William J. | Blaney, Thomas J. | Winn, Shelley R. | Sherman, Sandy S. | Doherty, Edward J. | Emerich, Dwaine F.

Article Type: Research Article

Abstract: Numerous studies have reported that adrenal chromaffin cell transplants, including encapsulated xenogeneic adrenal chromaffin cells, have analgesic effects. However, in addition to efficacy, the clinical utility of encapsulated xenogeneic adrenal chromaffin cells for treatment of chronic pain is dependent on the duration of cell viability in vivo, and their relative safety. The objectives of the present study in rats were to: (1) examine encapsulated calf adrenal chromaffin (CAC) cells for evidence of viable cells and continued release of analgesic agents after an extended period in vivo; (2) determine if intraventricular encapsulated CAC cells produce detectable adverse effects on behavioral/cognitive function; …and (3) test for evidence of host immune sensitization after an extended period of exposure to encapsulated xenogeneic adrenal chromaffin cells. Results of the present study suggest that some encapsulated CAC cells remain viable for nearly 1.5 years in vivo and continue to produce catecholamines and met-enkephalin. Post-explant device norepinephrine output was equivalent to amounts previously shown to produce analgesic effects with intrathecal implants. Encapsulated adrenal chromaffin cells also appeared relatively safe, even when implanted in the cerebral ventricals, with a lower side-effect profile than systemic morphine (4 mg/kg). There was no evidence that encapsulated CAC-cells implanted in the ventricles affected body weight, spontaneous activity levels, or performance in the delayed matching to position operant task which is sensitive to deficits in learning, memory, attention, motivation, and motor function. Finally, encapsulated CAC cells produced no detectable evidence of host immune sensitization after 16.7 months in vivo, although unencapsulated CAC cells produced a robust immune response even in aged rats. The results of the present study suggest that adrenal chromaffin cells remain viable in vivo for long periods of time, and that long-term exposure to encapsulated xenogeneic adrenal chromaffin cell implants appears relatively safe. Show more

Keywords: Adrenal chromaffin cells, Safety, Toxicity, Adverse effects, Side-effect profile

DOI: 10.3233/RNN-1997-111203

Citation: Restorative Neurology and Neuroscience, vol. 11, no. 1-2, pp. 21-35, 1997

Authors: Nógrádi, Antal | Vrbová, Gerta

Article Type: Research Article

Abstract: Volkensin is a neurotoxic lectin which, when injected into a peripheral nerve is retrogradely transported to the cell body and causes it to die. Accordingly, volkensin-affected peripheral nerves rapidly degenerate. It is, however, not clear whether axonal growth can take place within these degenerated nerves. In this study the ability of volkensin-treated and untreated degenerated peripheral nerves to support regeneration of healthy axons was compared. Four groups of animals were used, in Group 1 the peroneal nerve was cut and 10 days later the proximal stump of the deep tibial nerve was sutured to the distal stump of the peroneal …nerve (10 days after axotomy). In the second group of animals the peroneal nerve was treated with volkensin, 10 days later the proximal stump of the deep tibial nerve was connected to the distal section of the cut, thus giving a volkensin-treated peroneal nerve. In the third group, 10 days after the peroneal nerve was treated with volkensin, the proximal stump of the deep tibial nerve was connected directly to the extensor digitorum longus (EDL) muscle. In Group 4 the volkensin-treated peroneal nerve was left intact. Six weeks after surgical intervention the tension of both EDL muscles was recorded and the muscles were processed for histological visualisation of endplates and axons. EDL muscles from Group 1 animals produced 36.5 ± 11.3% S.E.M of maximal tetanic tension produced by the contralateral EDL muscle. Significantly less recovery of function was achieved by EDL muscles in Group 2 animals (9.3 ± 2.5%). Muscles from Group 3, where the healthy nerve was sutured directly into the EDL muscle that had been denervated by volkensin treatment had a significantly better recovery than Group 2 muscles (23 ± 3%). Sprouting of nerve fibres and proliferation of Schwann cells was observed in the muscles from Groups 1 and 3, but not in Group 2. Thus, volkensin-treated peripheral nerves provide a poor conduit for regenerating nerve fibres though muscles denervated, by treatment with volkensin, and can accept reinnervation by healthy nerves. The possible mechanisms that render the volkensin treated peripheral stump a poor conduit for healthy axons is discussed. Show more

Keywords: Peripheral nerve, Volkensin, Regeneration, Delayed reinnervation, Wallerian degeneration, Collateral sprouting

DOI: 10.3233/RNN-1997-111204

Citation: Restorative Neurology and Neuroscience, vol. 11, no. 1-2, pp. 37-45, 1997

Authors: Wu, Yangguan | Han, Kai | Wu, Wutian | Terzis, Julia K.

Article Type: Research Article

Abstract: Avulsion of the brachial plexus is considered the most severe injury of the peripheral nerve. The present study provides a description of the response of ChAT within the ventral horn of the rat cervical spinal cord following avulsion of the brachial plexus. The result demonstrates that the intensity of immunoreactivity of ChAT positive neurons and neuropil background increases in the first 3 days following avulsion and then decreases. The number of ChAT-positive motorneurons in the ventral horn in the lesion side is 84.4% compared to the normal side during the first 3 days post-avulsion, at 7 days the number of …ventral horn neurons drops to 64.4% and at 21 days post-avulsion it becomes 44.1%. In the sixth week post-avulsion, only 24.8% of the ventral horn neurons still persist. Show more

Keywords: Choline acetyltransferase, Spinal cord, Brachial plexus avulsion, Motor neurons

DOI: 10.3233/RNN-1997-111205

Citation: Restorative Neurology and Neuroscience, vol. 11, no. 1-2, pp. 47-54, 1997

Authors: Goldstein, Larry B.

Article Type: Research Article

Abstract: The recovery of beam-walking ability following a unilateral sensorimotor cortex lesion in the rat is hypothesized to be noradrenergically-mediated. We carried out two experiments to further test this hypothesis. In the first experiment, bilateral 6-hydroxydopamine locus coeruleus (LC) lesions or sham LC lesions were made 2 weeks prior to a right sensorimotor cortex suction-ablation lesion or sham cortex lesion. In the second experiment, unilateral left or right LC lesions or sham LC lesions were made 2 weeks prior to a right sensorimotor cortex lesion or sham cortex lesion. Beam-walking recovery was measured over the 12 days following cortex lesioning in …each experiment. Bilateral, unilateral left, and unilateral right LC lesions resulted in impaired recovery. These data provide additional support for the hypothesis that beam-walking recovery after sensorimotor cortex injury is, at least in part, noradrenergically mediated. Show more

Keywords: Cortex, Recovery, Motor Function, Locus coeruleus, Norepinephrine, Stroke, Trauma, Rat

DOI: 10.3233/RNN-1997-111206

Citation: Restorative Neurology and Neuroscience, vol. 11, no. 1-2, pp. 55-63, 1997

Authors: Terada, Nobuki | Bjursten, Lars M. | Papaloïzos, Michaël | Lundborg, Göran

Article Type: Research Article

Abstract: Gaps, 10 mm wide, in rat sciatic nerves were bridged by bioartificial nerve grafts consisting of a silicone tube containing seven longitudinally placed synthetic filaments, which were expected to serve as a scaffold for axonal growth. The filaments were made of non-resorbable material (polyamide [Ethilon® ]) or resorbable material (polydioxanon [PDS® ], polyglactin [Vicryl® ] or catgut). The purpose was to study the influence of resorbable materials on axonal regeneration and to choose, in the long term, the best filament material among the four. After 3 and 6 months, histological techniques were used to study the regenerated nerve structure. The …total axon number in the nerve segment distal to the silicone chamber was counted in all specimens at 6 months. The histological findings were different depending on the filament materials; all the three resorbable materials showing significantly larger numbers of axons than polyamide (non-resorbable). All materials were covered with several layers of more or less flattened cells. These results indicate that resorbable filaments are superior to non-resorbable filaments when used as a scaffold inside a silicone tube, and polyglactin seems ideal for this purpose. Show more

Keywords: Nerve regeneration, Axonal growth, Nerve graft, Silicone chamber, Resorbable filament, Biomaterial, Axon counting

DOI: 10.3233/RNN-1997-111207

Citation: Restorative Neurology and Neuroscience, vol. 11, no. 1-2, pp. 65-69, 1997

Authors: Hoane, M.R. | Raad, C. | Barth, T.M.

Article Type: Research Article

Abstract: Following brain injury there is an excessive release of glutamate, a reduction in levels of cellular Mg+ + , and the generation of oxygen free radicals. These processes may contribute to the severity of the behavioral impairments seen following brain injury by leading to secondary neuronal degeneration. The present experiment investigates the relative effects of three drugs (MK-801, an NMDA antagonist; magnesium chloride, an NMDA antagonist; and N-tert-butyl-α-phenylnitrone (PBN), an anti-oxidant and free radical scavenger) which disrupt different aspects of the pathophysiological process, in reducing these impairments. Direct comparisons of these drugs may determine if one treatment is more effective …than another, or if one is detrimental. In addition, the effects of combination treatments including PBN and MK-801 or MgCl2 were examined. These combination treatment were aimed at the possibility of potentiating the beneficial effects observed after administration of these agents alone. Rats received unilateral electrolytic lesions of the somatic sensorimotor cortex followed by a regimen of MK-801 (1 mg/kg), MgCl2 (1 mmol/kg), PBN (100 mg/kg), MK-801 + PBN (1 mg/kg, 100 mg/kg), MgCl2 + PBN (1 mmol/kg, 100 mg/kg), or saline (1 ml/kg) beginning 15 min following injury. Rats were tested on several sensorimotor tasks (i.e. forelimb placing and foot-fault) for 43 days following the cortical lesions. Rats receiving any of the single or combination drug treatments showed a significant facilitation of recovery on the sensorimotor tasks compared to saline control rats. On one behavioral test (i.e. foot-fault) there was a significant further enhancement of the recovery by combination treatments compared to the single treatment groups. These data are consistent with the idea that excessive release of glutamate, reduction in Mg+ + levels, and free radical generation contribute to the severity of the behavioral impairments following cortical injury, and that arresting these processes results in a facilitation of behavioral recovery. Anatomical analysis showed that all drug treatments decreased the amount of atrophy seen in the ipsilateral striatum. Show more

Keywords: Secondary brain damage, Sensorimotor behavior, Neuroprotection, Glutamate, Recovery of function, Magnesium chloride, MK-801, PBN

DOI: 10.3233/RNN-1997-111208

Citation: Restorative Neurology and Neuroscience, vol. 11, no. 1-2, pp. 71-82, 1997

Authors: Stackman, Robert W. | Bartolomeo, Adam C. | Walsh, Thomas J.

Article Type: Research Article

Abstract: High-affinity choline transport (HAChT) is the rate limiting step in the synthesis of acetylcholine (ACh). The activity of HAChT and the binding of its selective inhibitor, [3 H]hemicholinium-3 (HC-3) are affected by a number of exogenous and endogenous factors. Previous experiments demonstrated that Vitamin E pretreatment could prevent the decrease in HAChT and the cognitive deficits induced by the cholinotoxin AF64A [38]. To further examine this effect these experiments determined whether Vitamin E would alter the efficacy of both irreversible (AF64A) and reversible (HC-3) inhibitors of HAChT. In Experiment 1, rats were pretreated with Vitamin E (50 mg/kg), 24 h …and 15 min, prior to bilateral icv injection of AF64A (0, 0.75, 1.5, or 3.0 nmol). HAChT was assessed in hippocampal synaptosomes, 14 days following surgery. Vitamin E prevented the dose-dependent AF64A-induced inhibition of HAChT in the hippocampus (HPC). In a second experiment, rats were pretreated with Vitamin E as above, and infused (icv) with the reversible inhibitor of HAChT, HC-3 (20 μg), or CSF. HAChT in the HPC was assessed 30 min, 4, 12, or 24 h after injection. HC-3 produced a significant decrease of HAChT (58%) that was maximal at 4 h and recovered by 24 h. Vitamin E significantly attenuated, but did not prevent, the inhibition of HAChT produced by HC-3. These experiments demonstrate that Vitamin E pretreatment can attenuate the effects of both reversible and irreversible inhibitors of HAChT. These data are discussed in terms of potential underlying mechanisms. It is possible that the neuroprotectant effects of Vitamin E on both reversible and irreversible inhibitors of HAChT reflect an action at the choline carrier and not an antioxidant effect. Show more

Keywords: Vitamin E, AF64A, Hemicholinium-3, Anti-oxidants, Choline uptake

DOI: 10.3233/RNN-1997-111209

Citation: Restorative Neurology and Neuroscience, vol. 11, no. 1-2, pp. 83-89, 1997

Authors: De Brabander, J.M. | Kolb, B.

Article Type: Research Article

Abstract: The anterior midline cortex of rats was removed on postnatal day 10. The development of layer II, III and V pyramidal cells in the tissue that subsequently formed the presumptive medial frontal cortex in these animals was studied in Golgi-Cox stained material on postnatal days 15, 25, 35, and 120. The results showed that the number of branch segments of both basilar and apical dendrites were significantly reduced relative to controls at the early developmental stages but by adulthood all regions analyzed were similar in operates and controls. Thus, the cells migrating into the lesion area were delayed in development …but did eventually grow to resemble cells that were in the same region in normal controls. This anatomical development correlates with the functional recovery of animals with day 10 frontal lesions in other studies, and suggests that the growth of this tissue may play a role in functional recovery. Show more

Keywords: Functional recovery, Dendritic arborization, Branch segments, Development, Prefrontal cortex, Plasticity

DOI: 10.3233/RNN-1997-111210

Citation: Restorative Neurology and Neuroscience, vol. 11, no. 1-2, pp. 91-97, 1997

Authors: Li, Ying J. | Hartman, Boyd K. | Faris, Patricia L. | Low, Walter C.

Article Type: Research Article

Abstract: The retrosplenial cortex (RSC) is a target of the forebrain cholinergic projecting system. It receives extensive cholinergic innervation from the medial septal nucleus and the diagonal band of Broca. These cholinergic afferents travel along the paths of cingulate bundle and fornix. In the present study we investigated the ability of cholinergic fetal septal grafts to reinnervate the deafferented RSC. Four groups of rats were used: (1) normal control rats (NC); (2) rats with bilateral transections of the cingulate bundle (CgX); (3) rats with simultaneous lesions of both the cingulate bundle and the fornix (FX), and (4) rats with intra-retrosplenial fetal …septal grafts and lesions in both cingulate bundle and the fornix (RSCsep-TPL). We found that lesions in the cingulate bundle alone produced a modest reduction of cholinergic innervation whereas lesions in both the fornix and cingulate bundle resulted in a complete loss of cholinergic inputs in this area, indicating that both the cingulate bundle and the fornix are involved in mediating cholinergic projections from the septal-diagonal area to the RSC. Transplantation of cholinergic fetal septal neurons into the RSC of animals with simultaneous lesions in both the fornix and cingulate bundle restored the cholinergic innervation pattern to that which is typical of the normal septo-retrosplenial inputs. These results provide the neuroanatomical basis for behavioral studies which have documented graft-mediated recovery of spatial memory function in rats with lesions of the cholinergic septo-retrosplenial pathways Show more

Keywords: Retrosplenial cortex, Cingulate bundle, Fornix, Cholinergenic projections, Lesions

DOI: 10.3233/RNN-1997-111211

Citation: Restorative Neurology and Neuroscience, vol. 11, no. 1-2, pp. 99-108, 1997

Authors: Angelov, Doychin N. | Neiss, Wolfram F. | Gunkel, Andreas | Streppel, Michael | Guntinas-Lichius, Orlando | Stennert, Eberhard

Article Type: Research Article

Abstract: Hypoglossal-facial anastomosis (HFA), used for the treatment of facial palsy, was performed in adult Wistar rats. For 7–224 days post operation (DPO), half of the animals were kept on standard laboratory food and half received food pellets containing 1000 ppm of the Ca2+ channel blocker nimodipine. The postoperative neurotization of facial muscles in these two groups was traced by comparing numbers of all retrogradely labeled neurons after injection of HRP into the whiskerpad muscles. In unoperated animals, injection of HRP labeled 1254 ± 54 neurons. Immediately after HFA, this number dropped to zero. The treatment with nimodipine yielded two …beneficial effects. (1) In the early phase of regeneration (until 28 DPO), it accelerated the sprouting of hypoglossal axons into the facial periphery; (2) In the final phase, it suppressed the axonal sprouting from both, hypoglossal and facial stumps. In this way nimodipine fully prevented the postoperative hyperinnervation, i.e. the projection of more hypoglossal plus facial motoneurons to the whiskerpad muscles than under normal conditions. Show more

Keywords: Rat, Facial nerve, Hypoglossal nerve, Nerve suture, Retrograde tracing, Nimodipine, Neuron number

DOI: 10.3233/RNN-1997-111212

Citation: Restorative Neurology and Neuroscience, vol. 11, no. 1-2, pp. 109-121, 1997