Restorative Neurology and Neuroscience - Volume 7, issue 1

Authors: Earl, Christopher D. | Frodl, Eva M. | Pupeter, Sigrid C. | Oertel, Wolfgang H. | Kupsch, Andreas

Article Type: Research Article

Abstract: This study investigated the potential neurotoxic effects of cyclosporin A (CyA) on allogeneic foetal rat ventral mesencephalic (VM) grafts in the 6-hydroxydopamine rat model of Parkinson's disease. Despite its use in the clinical neural grafting situation, the safety of the CyA treatment concerning graft survival and function has not been demonstrated in systematical animal studies. Three groups of grafted rats were treated with either 10 or 20 mg/kg cylcosporin A daily for 6 weeks. Analysis of graft function and development within the different immunosuppression regimes showed no significant differences between any parameters assessed (rotational behaviour and graft survival). It is …concluded that high doses of cyclosporin A do not adversely influence survival and function of rat-to-rat foetal allogeneic VM grafts. Show more

Keywords: Cyclosporin A, Parkinson's disease, Foetal ventral mesencephalon, Rat, Neural grafting, Immunosuppression

DOI: 10.3233/RNN-1994-7101

Citation: Restorative Neurology and Neuroscience, vol. 7, no. 1, pp. 1-4, 1994

Authors: Levin, Barry E. | Pan, Shijun | Dunn-Meynell, Ambrose

Article Type: Research Article

Abstract: Norepinephrine (NE) has been implicated in cerebral plasticity and recovery of function after brain injury. To examine the status of noradrenergic mechanisms in the brain following traumatic brain injury (TBI), male Sprague-Dawley rats underwent right sensorimotor cortex contusions and were observed for the next 30 days for recovery of motor function by measurement of the time taken to perform a modified beam walking task! At 30 days, their brains were assayed by receptor autoradiography for αr - and α2 -adrenoceptor binding with 1 nM [3 H]prazosin and 1 nM [3 H]paraminoclonidine, respectively. One day after contusion, TBI rats took 60% …longer to run the beam than sham-lesioned controls. Run times were directly proportional (r = 0.784; P = 0.012) to lesion volume determined at 30 days. The motor deficit persisted for 8 days, after which TBI and control rats had similar run times, largely due to increased run times in sham rats. At 30 days, TBI rats had a generalized, bilateral decrease in [3 H]prazosin binding across all brain areas read (F[l,13] = 9.23; P = 0.009) with specific 12%–21% decreases in the cortex contralateral to the lesion and bilaterally in the dorsomedial hypothalamic and three thalamic nuclei. On the other hand, [3 H]paraminoclonidine binding did not differ from sham lesion controls in any brain area of TBI rats. Thus, unilateral TBI is followed by widespread, bilateral changes in α1 -adrenoceptor binding which would leave the animal vulnerable to any factors which reduced the access of NE to its postsynaptic adrenoceptors. This is compatible with the observation that α1 -antagonists and α2 -agonists can transiently reinstate the motor deficit after recovery has occurred. Show more

Keywords: Brain injury, Head trauma, Norepinephrine, Recovery of function, Plasticity

DOI: 10.3233/RNN-1994-7102

Citation: Restorative Neurology and Neuroscience, vol. 7, no. 1, pp. 5-12, 1994

Authors: Prasad, Kedar N. | Carvalho, Erika | Kentroti, Susan | Edwards-Prasad, Judith | La Rosa, Francisco G. | Kumar, Sanjay | Freed, Curt R. | Vernadakis, A.

Article Type: Research Article

Abstract: The use of fetal central nervous system (CNS) tissue in neural transplants has ethical, availability and some biological limitations. In order to overcome these problems, homogeneous populations of specific neurons in vitro should be established. Transformed nerve cells such as neuroblastoma cells (NBP2 ) in culture can serve as one of the sources of donor neurons in neural transplants provided they can be induced to differentiate terminally. This study showed that treatment of murine neuroblastoma (NBP2 ) cells with 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (R020-1724, an inhibitor of cyclic nucleotide phosphodiesterase), and β-carotene for a period of 3 days followed by X-irradiation with 20 …Gy or above produced 100% terminally differentiated cells. These differentiated NB cells had long and extensive neurites, contained elevated levels of tyrosine hydroxylase (TH) activity and very low levels of MHC class I and II antigens, and were non-tumorigenic. The viability of differentiated NB cells when determined on the criteria of attachment efficiency, re-extension of neurites and presence of TH after replating was only 9%. This was in contrast to the trypan blue exclusion technique which showed that over 90% of differentiated NB cells in culture were viable. Show more

Keywords: Neuroblastoma, Differentiation, Viability

DOI: 10.3233/RNN-1994-7103

Citation: Restorative Neurology and Neuroscience, vol. 7, no. 1, pp. 13-19, 1994

Authors: Povlsen, B. | Stankovic, N. | Danielsson, P. | Hildebrand, C.

Article Type: Research Article

Abstract: Hand injuries with nerve lesions often leave the patient with a persistent sensory deficit, particularly with respect to glabrous skin. The present study examines axonal regeneration in the foot branch of the superficial peroneal nerve (fSPN) and the lateral plantar nerve (LPN), supplying hairy skin and glabrous skin together with some intrinsic muscles, respectively, after sciatic nerve lesions in the rat. Following crush lesions, the number of myelinated axons is normal in the fSPN, and the occurrence of C-fibers appears slightly reduced. In the LPN, the numbers of myelinated axons and C-fibers are both significantly increased. Post-crush regenerated myelinated fSPN …and LPN axons show normal size ranges, but the proportion of small myelinated axons is increased. After neurotomy and suture, the numbers of myelinated axons and C-fibers in the fSPN are not significantly different from normal. The LPN exhibits a significantly increased number of myelinated axons, but the number of C-fibers is not significantly abnormal. In both nerves, the myelinated axons present an abnormally narrow size range. These findings show that the quantitative outcome of regeneration in a nerve innervating glabrous skin (and some intrinsic muscles) differs significantly from that of branches to hairy skin of the foot, with respect to myelinated as well as unmyelinated axons. To what extent these differences mirror functional differences awaits elucidation. Show more

Keywords: Rat, Foot nerves, Nerve injury, Regeneration, Electron microscopy, Axon number, Fiber size distribution

DOI: 10.3233/RNN-1994-7104

Citation: Restorative Neurology and Neuroscience, vol. 7, no. 1, pp. 21-27, 1994

Authors: Sakaguchi, Tateo | Yamada, Kazuo | Wanaka, Akio | Kohmura, Eiji | Yuguchi, Takamichi | Taneda, Mamoru | Kataoka, Kazuo | Tohyama, Masaya | Hayakawa, Toru

Article Type: Research Article

Abstract: The present study examined whether expression of basic fibroblast growth factor receptor (bFGFR) messenger ribonucleic acid (mRNA) was upregulated by focal ischemia. We have studied the in situ hybridization autoradiography for bFGFR mRNA in the rat model of middle cerebral artery (MCA) occlusion. Male Wistar rats were used for occlusion of the left MCA, and were sacrificed 1, 3, 7 and 14 days after MCA occlusion. In situ hybridization was performed on the brain sections of these animals and sham controls by using 35 S-labeled antisense and sense (control) RNA probes for rat bFGFR. Expression of bFGFR mRNA was observed …in the periinfarcted area of the rats within 1-14 days after MCA occlusion. Expression was evident in the whole hemisphere of the infarcted side, especially at 1 and 3 days after ischemia, but no expression was detected in the contralateral side. On microautoradiograms, the signals of bFGFR mRNA were detected in both neurons and non-neural cells located in the periinfarcted area. Upregulation of bFGFR mRNA detected in the periinfarcted brain tissue suggests that receptor-mediated action of bFGF may be related to preservation of neurons injured by ischemia. Show more

Keywords: In situ hybridization, Fibroblast growth factor, Receptor, Focal ischemia, Cerebral infarction, Autoradiogram

DOI: 10.3233/RNN-1994-7105

Citation: Restorative Neurology and Neuroscience, vol. 7, no. 1, pp. 29-36, 1994

Authors: Vandertop, William P. | de Vries, Willem B. | Notermans, Nicolette C. | Tulleken, Cees A.F. | Gispen, Willem H.

Article Type: Research Article

Abstract: While the regenerating capacity of peripheral nerves has been the subject of intensive study, little is known about the regenerative capacity of the autonomic nervous system. Using an animal model, where the pupil diameter of the eye in the rat serves as a parameter of autonomic function, we studied whether systemic treatment with the neuropeptide Org 2766, a synthetic ACTH4-9 , analogue, facilitates the functional recovery of parasympathetic nerve fibres after transection, and after a crush lesion of the oculomotor nerve. By simply photographing the rat's pupil under standardised conditions, we show that sectioning the oculomotor nerve leads to an …immediate mydriasis, followed by spontaneous regeneration in 30 days. Systemic treatment with an ACTH4-9 analogue had no effect on the rate or quality of recovery. However, systemic treatment with an ACTH4-9 analogue after a crush lesion of the oculomotor nerve (spontaneous regeneration time 16 days) did enhance the speed of recovery of the parasympathetic nerve fibres in the oculomotor nerve, especially in the initial stages of regeneration. We conclude that the animal model used in this study is valuable for studying the regenerative capacity of the autonomic nervous system and the influence of neurotrophic peptides on autonomic neuropathies. Evidence is presented that synthetic ACTH4-9 analogue exerts beneficial neurotrophic effects, not only in peripheral sensorimotor neuropathies but also in autonomic neuropathies. Show more

Keywords: Autonomic neuropathy, ACTH4-9 analogue, Neuropeptides, Nerve regeneration

DOI: 10.3233/RNN-1994-7106

Citation: Restorative Neurology and Neuroscience, vol. 7, no. 1, pp. 37-43, 1994

Authors: Midha, Rajiv | Mackinnon, Susan E. | Evans, Peter J. | Hunter, Daniel A. | Becker, Laurence E.

Article Type: Research Article

Abstract: The pattern and temporal sequence of histopathological events in a rat nerve allograft model were evaluated. Following grafting and varying survival periods (from 1 to 30 weeks), the host and donor nerve were removed and assessed by light and electron microscopy. Nerve allografts underwent Wallerian degeneration and rejection. Wallerian degeneration was the dominant pathologic process at weeks 1 and 2 after engraftment. Histologic rejection started as an epineurial process at weeks I and 2, became progressively endoneurial and was most prominent at 4 and 6 weeks after engraftment. Rejection was accompanied by evidence of graft Schwann cell and endoneurial tube …loss. The rejection process delayed, but did not prevent, nerve regeneration by the host. Regeneration of fine neurofilament-positive axonal sprouts into the proximal portions of the graft was observed as early as week 2. Subsequently, regeneration occurred through the periphery and around the exterior of the rejected nerve allograft fascicle. Regenerating axons were accompanied by S100 protein reactive Schwann cells and newly synthesized laminin-positive endoneurial tubes. Regenerating axons reinnervated the distal host segment at week 8 and increased in number and myelination thereafter. The observations of rejection and regeneration through nerve allograft segments are discussed in reference to previous studies. Show more

Keywords: Transplantation, Nerve regeneration, Allograft, Nerve injury, Rat, Laminin, Schwann cell

DOI: 10.3233/RNN-1994-7107

Citation: Restorative Neurology and Neuroscience, vol. 7, no. 1, pp. 45-57, 1994

Article Type: Research Article

DOI: 10.3233/RNN-1994-7108

Citation: Restorative Neurology and Neuroscience, vol. 7, no. 1, pp. 59-59, 1994