Restorative Neurology and Neuroscience - Volume 17, issue 2-3

Authors: Kolb, Bryan | Cioe, Jan | Whishaw, Ian Q.

Article Type: Research Article

Abstract: Purpose: The purpose of this study was to compare the behavioural and anatomical effects of unilateral motor cortex ablation in neonatal, infant, and adult rats. Methods: Rats were given unilateral lesions of the motor cortex on the day of birth (P1), at ten days of age (P10), or in adulthood. They were trained on several motor tasks (skilled forelimb reaching, beam traversing, tongue extension), general motor activity, and a test of spatial learning (Morris water task). …Results: Although all lesion groups were equally impaired at skilled reaching with the forelimb contralateral to the lesion, rats with P1 lesions also were impaired at traversing a narrow beam and at learning the Morris task. Gross anatomical analyses revealed that the P1 rats had smaller brains than the other groups, a result that may account for the larger behavioural deficits in the P1 group. Analysis of Golgi-Cox stained neurons showed that relative to control groups, all lesion groups showed an increase in dendritic length in the basilar dendrites of layer III pyramidal cells and, paradoxically a decrease in length of the apical dendrites of the same cells. Conclusions: The bilateral alterations in dendritic organization following the motor cortex lesions suggest that there has been a bilateral reor-ganization of intrinsic cortical connectivity following motor cortex lesions at any age. These alterations in connectivity are likely not identical in the young and adult animals, however, because relative to controls, both the young operated groups, but not the adult group, showed a bilat-eral drop in spine density in the basilar dendrites of layer V pyramidal cells. These findings are discussed with respect to the idea that there may be critical ages in development in which animals can use anatomical modifications to compensate for deficits produced by cortical injury. Show more

Keywords: recovery of function, corticospinal tract, motor cortex

Citation: Restorative Neurology and Neuroscience, vol. 17, no. 2-3, pp. 61-70, 2000

Authors: Görlach, Christoph | Hortobágyi, Tibor | Hortobágyi, Szabolcs | Benyó, Zoltán

Article Type: Research Article

Abstract: Purpose: The aim of the present study was to assess the effects of neuronal nitric oxide synthase (NOS I) inhibitors and a combination of NOS I and NOS II inhibitors on lesion volume after experimental brain injury. Methods: Cold lesion of the brain was induced by application of a precooled (.... 78 °C) copper cylinder to the intact dura of the rat for 6 s. Brains were removed 24 h after the injury and lesion volume determined using the …triphenyltetrazolium-chloride method. Results: The specific NOS I inhibitor 3-bromo-7-nitroindazole (Br-7-NI) reduced lesion volume significantly by 21 % compared with the vehicle control. In contrast, 7-nitroindazole had no effect on lesion volume. When aminoguanidine, a specific NOS II inhibitor, was adminis-tered after Br-7-NI, lesion volume was significantly reduced but not significantly more than with either compound alone. Conclusion: Brain injury after cold lesion is partly mediated by NOS I activity and can be attenuated successfully with Br-7-NI, while coin-hibition of NOS II does not improve the outcome significantly. Show more

Keywords: Nitric oxide synthase, NOS I, NOS II, 3-bromo-7-nitroindazole, 7-nitroindazole, aminoguanidine, cold brain injury, rat

Citation: Restorative Neurology and Neuroscience, vol. 17, no. 2-3, pp. 71-76, 2000

Authors: Payne, Bertram R. | Lomber, Stephen G.

Article Type: Research Article

Abstract: Purpose: Damage of primary visual cortex in adult humans, monkeys and cats severely disrupts vision by disconnecting much of the cogni-tive processing machinery of extrastriate cortex from its source of visual signals in the retina. Equivalent lesions sustained early in life result in partial sparing of visual processing functions and evidence from the mature brain suggests that systematic training procedures can ameliorate the impact of remaining deficits. The purpose of the present work was to use …two reflex-based, visual detection and orienting tasks to test for the therapeutic effects of reha-bilitative training in cats that sustained lesions of primary cortical areas 17 & 18 in adulthood, and to test whether similar training is of benefit to cats that incurred equivalent lesions at one month-of-age (P28) or shortly after birth (P1). Methods: Cats were trained to attend to static visual and auditory cynosures and tested on their ability to disengage the cynosure and orient towards a target presented in the periphery of the testing arena. Targets were: 1) a high contrast, dark, moved rod; 2) an illuminated static light-emitting diode (LED); and 3) a broad band, white noise, sound stimulus. Results: On Task 1, cats with lesions of areas 17 & 18 sustained in adulthood are markedly impaired whereas cats that sustained lesions in infancy exhibit partial sparing of the visual operations underlying this task. With training, the performance of all cats improved. On Task 2, performance by the adult-lesion and the P1-groups were markedly impaired, whereas the P28-group exhibited partial sparing. On Task 3, per-formance by all groups was uniformly high. No detectable benefits of training were identified on tasks 2 and 3. Conclusions: Overall, the results show that cats incur definite benefits of training following visual cortex lesions regardless of whether the lesions were sustained early in life or later, but the benefits are limited to specific types of visual stimuli. Show more

Citation: Restorative Neurology and Neuroscience, vol. 17, no. 2-3, pp. 77-88, 2000

Authors: Spillmann, Lothar | Laskowski, Wolfgang | Lange, Klaus W. | Kasper, Ekkehard | Schmidt, Dieter Dieter

Article Type: Research Article

Abstract: Purpose. To study and follow-up achromatopsia, prosopagnosia, and topographagnosia in a patient who suffered a bilateral stroke of the posterior cerebral arteries. Methods. Ophthalmological, neuropsychological and neuroradiological examinations were conducted over a span of 3 years to assess the amount of brain damage and look for signs of functional recovery. Results. After the onset of achromatopsia, perception of the color green re-appeared first, followed by red, yellow, and brown. Blue which had appeared entirely …black was last to return. While reading and color naming have largely recovered, color discrimination after three years remains poor especially in dim lighting. Similarly, with prosopagnosia, while the patient has learn to identify people (including photographs) by individual features, his ability to perceive and recognize faces and facial expressions holistically remains severely impaired. Recognition of streets, houses, and topographical layouts also continues to be affected, while the perception of speed and distance has somewhat improved. Perimetry further suggests a mild improvement of the superior hemianopia in his visual fields. Conclusions. Although major deficits in color, face and place perception remain, some functions impaired by the stroke have returned par-alleling a partial recovery from the brain lesion as demonstrated by NMR. Show more

Keywords: Achromatopsia, prosopagnosia, topographical agnosia, recovery, stroke

Citation: Restorative Neurology and Neuroscience, vol. 17, no. 2-3, pp. 89-103, 2000

Authors: Sabel, Michael | Kiessling, Marika | Sommer, Clemens

Article Type: Research Article

Abstract: Purpose: Transforming growth factor beta 2 (TGFâ2) is a multifunctional cytokine thought to play a crucial role in neuronal growth, differ-entiation and survival. In the cortex of adult rats, TGFâ2 is constitutively expressed in a subset of neurons and astrocytes. In the present study we analyzed whether TGFâ2 is also present in intrastriatal transplants of cortical anlage. In addition we investigated the temporo-spatial expression pattern of TGF2 in âthe surrounding host striatum. Methods: …Cortical primordia of rat fetuses (E14) were stereotactically grafted into the rostral striatum of adult recipient rats. Grafts were allowed to differentiate for 1, 2, 3, 4, 8 weeks or one year, respectively, followed by morphological and immunohistochemical analysis. Results: From week 2 on, TGFâ 2-immunoreactivity (IR) was detectable in transplanted neurons. Within the graft, GFAP-IR was already present one week after transplantation, whereas TGFâ2-immunostained astrocytes were first seen after 2 weeks. One year after transplanta-tion, TGFâ2 positive neurons and astrocytes were still present. In the host striatum and at the graft-host interface an increase of TGFâ2-immu-noreactive astrocytes first occured after one week both in grafted animals and in sham-operated (lesioning without grafting) rats. Conclusions: Our data suggest that at least a subpopulation of transplanted neurons develops a phenotype as cortical neurons in situ with respect to TGFâ2 expression. Upregulation of astrocytic TGFâ2 expression within the graft, however, is due to the trauma imposed by the transplantation procedure rather than an intrinsic differentiation program of co-grafted astrocytes. Show more

Keywords: glial fibrillary acidic protein, graft, immunohistochemistry, neural transplantation, rat, ,

Citation: Restorative Neurology and Neuroscience, vol. 17, no. 2-3, pp. 105-112, 2000

Authors: Lan, Chyn Tair | Liu, Jiang Chuan | Ling, Eng Ang | Cheng, Min Hsiung | Youn, Su Chung

Article Type: Research Article

Abstract: Purpose: To investigate the relationships between the axonal sprouting and target neurotization by central neurons after nerve heterocon-nection. Methods: Unilateral (right) vagal-hypoglossal nerve anastomosis (VHA) was performed in adult cats. Following 3315 days postoperation (dpo), quantitative analyses and ultrastructural changes in the proximal portion of the vagal-hypoglossal heteroconnected nerve as well as the time course of neuronal regeneration were studied. Along with this, horseradish peroxidase (HRP) retrograde tracing technique was used to …label the neurons of dorsal motor vagal nucleus (DMV) and nucleus ambiguus (NA) to ascertain if target neurotization was established. Results: The contralateral (left) intact vagus nerve proximal to the level of ansa cervicalis showed an average of 33 ± 1 myelinated and 74 ± 4 unmyelinated axons in 727 µm 2 sectional area of the nerve. In the heteroconnected nerve at the corresponding level just proximal to the anastomosis site, there was a marked increase in the number of small axons sprouting from the unmyelinated nerve fibers between 18 and 25 dpo. The number of these axonal sprouts appeared to decline at 32 dpo but its increase of 131 % was sustained until the late regeneration stage at 315 dpo when compared with the contralateral nerve serving as a control. The mean number of myelinated axons per area unit (727 µm 2 ) was reduced to 18 at 3 dpo but was immediately restored to the normal range at 7 dpo. The retrograde labelling of neurons in both the DMV and NA was first detected at 22 dpo and was progressively increased peaking by about 67 dpo. Conclusions: We conclude that compared with the unmyelinated axons, the myelinated axons may acquire a superior interaction with the new target. Furthermore, the postoperative neurotization of tongue muscles may initiate and facilitate the retraction of the redundant axonal sprouts. Show more

Keywords: Vagus nerve, Hypoglossal nerve, Nerve heteroconnection, Axonal sprouting, Electron microscopy

Citation: Restorative Neurology and Neuroscience, vol. 17, no. 2-3, pp. 113-124, 2000

Authors: Hirsch, Sabine | Labes, Monika | Bähr, Mathias

Article Type: Research Article

Abstract: Purpose: Exogenously applied BDNF has been shown to rescue rat retinal ganglion cells (RGCs) from axotomy-induced apoptotic death, presumably via activation of its high affinity receptor TrkB. Since both TrkB and BDNF are endogenously expressed in RGCs, auto- or para-crine neurotrophic loops in the retina may be involved. In the present study, we investigated whether expression levels of BDNF, TrkA, TrkB, TrkC and p75 protein in RGCs are specifically regulated following axonal lesion and during regeneration …of optic fibres in the adult rat. Methods: By double labelling retinal cryosections with Fluorogold and respective antibodies we determined the percentage of RGCs expressing the above-mentioned markers. In addition, mRNA levels of BDNF and TrkB were measured using quantitative RT-PCR. Results: Compared to controls the number of BDNF-positive RGCs increased twofold 2 days after axotomy and the percentage of RGCs expressing TrkB was elevated by 50 %. Correspondingly, mRNA levels of BDNF increased about twofold 2 days after axotomy. During regen-eration, the percentage of BDNF-immunoreactive RGCs was further elevated compared to axotomy alone. The number of TrkA-positive RGCs doubled after axotomy, whereas no significant change in TrkC expression was observed. P75 expression was not detected in adult rat RGCs. Conclusion: Our results suggest that intrinsic rescue mechanisms may contribute to short term neuronal survival and axonal regeneration of RGCs after axonal lesions. Show more

Keywords: Retinal ganglion cells, neurotrophins, BDNF, TrkB, p75NGFR

Citation: Restorative Neurology and Neuroscience, vol. 17, no. 2-3, pp. 125-134, 2000

Authors: Tariq, Mohammad | Arshaduddin, Mohammed | Biary, Nabil | Al Deeb, Saleh | Al Moutaery, Khalaf

Article Type: Research Article

Abstract: Purpose: Diethyldithiocarbamate (DEDC) is a substituted dithiocarbamate that is metabolically interconvertible with disulfiram (Ant-abuse). In recent years DEDC has received considerable attention because of its clinical applications and potential role in mediating both the toxic and therapeutic actions of disulfiram which is frequently used for alcohol aversion therapy. DEDC is known for its multiplicity of action that exerts both pro- and antioxidant effects. In rodents DEDC has been shown to produce neuroprotective …as well as neurotoxic effects. The purpose of this study was to examine the effect of DEDC on neurological recovery following sciatic nerve crush injury (SNCI) in rats. Methods: Adult female Wistar rats were subjected to SNCI with a haemostat under deep anaesthesia. The animals were orally treated with DEDC at the doses of 250 mg/kg, 500 mg/kg and 750 mg/kg body weight 1 hr before SNCI and then once daily for 60 days. The animals were observed for sciatic functional index (walking deficit), electrophysiological and histological changes. Vitamin E level was measured to deter-mine antioxidant status of sciatic nerve. Results: Crush injury to the sciatic nerve resulted in a significant impairment of functional response which gradually recovered over a period of 22 days. Treatment of animals with DEDC caused a significant delay in functional recovery which was accompanied by poor histo-logical and electrophysiological outcome. Prooxidant effect of DEDC is quite evident from a significant decrease in vitamin E levels in both injured and uninjured sciatic nerves. Conclusions: Our results demonstrate that exposure to DEDC adversely affects recovery from peripheral nerve injury. The delay may to some extent be attributed to DEDC induced oxidative stress. Show more

Keywords: crush injury, diethyldithiocarbamate, regeneration, sciatic nerve, vitamin E

Citation: Restorative Neurology and Neuroscience, vol. 17, no. 2-3, pp. 135-141, 2000

Article Type: Abstract

Citation: Restorative Neurology and Neuroscience, vol. 17, no. 2-3, pp. 143-154, 2000

Article Type: Correction

Citation: Restorative Neurology and Neuroscience, vol. 17, no. 2-3, pp. 155-155, 2000