Restorative Neurology and Neuroscience - Volume 9, issue 2

Authors: Prasad, Renuka M. | Dose, John M. | Dhillon, Harbhajan S. | Carbary, Timothy | Kraemer, Philipp J.

Article Type: Research Article

Abstract: This study examined the effects of (D)-amphetamine, methoxamine (an al-adrenergic receptor agonist), and prazosin (an al-adrenergic receptor antagonist) on the behavioral outcome of lateral fluid percussion brain injury. Rats trained to perform a beam walking task were subjected to brain injury of moderate severity (2.1–2.2 atm). At 10 min after injury, rats were treated with amphetamine, methoxamine or prazosin at two different dose levels. Amphetamine-treated animals displayed significantly lower impairment in beam walking ability from days 1 to 5 after brain injury. Neither methoxamine nor prazosin significantly affected the impairment in beam walking ability from day 1 to day 7 …after injury. However, prazosin treatment at both dose levels increased the post-injury mortality and the incidences of failure to recovery from hemiplegia. Amphetamine-treatment at 4 mg/kg, but not at 2 mg/kg, improved the spatial learning abilities of the injured animals. Neither methoxamine nor prazosin affected the spatial learning abilities. These results indicate that amphetamine facilitated beam walking recovery and improved cognitive function after concussive fluid percussion injury. Although the methoxamine experiments suggest that the norepinephrine-α1 -adrenergic receptor system may not be involved in the pathophysiology of fluid percussion brain injury, our results with amphetamine (beneficial effects) and prazosin (deleterious effects) and the results observed in other models of brain injury point out that further investigations are necessary to understand the role of a1-adrenergic receptors in brain injury. Show more

Keywords: Fluid percussion brain injury, Norepinephrine, a1 Adrenergic receptor-agonists and antagonists, Behavioral deficits

DOI: 10.3233/RNN-1995-9201

Citation: Restorative Neurology and Neuroscience, vol. 9, no. 2, pp. 65-75, 1995

Authors: Serfaty, C. | Soroker, N. | Glicksohn, J. | Sepkuti, J. | Myslobodsky, M.S.

Article Type: Research Article

Abstract: Experimental animals with large posterior-cortical lesions develop disturbances of visual perception and visually-guided behavior in the contralateral space, resembling the syndrome of unilateral spatial neglect (USN) in humans. The visuo-motor performance in the ignored space is recovered some time following additional lesion inflicted to the contralesional superior colliculus or section of the intercollicular pathways. Based on the model that explains this recovery by disinhibition of the ipsilesional superior colliculus (the ‘Sprague effect’) Posner and Rafal [37] proposed that ipsilesional monocular occlusion could possibly reduce the ‘tone’ of contralesional collicular neurons thereby removing an important contributor of hemineglect. A group of …twenty-six right-hemisphere-damaged patients with USN was given a cancellation task under binocular and monocular (left and right) viewing conditions. Thirteen patients showed amelioration of left hemineglect in conditions of left-monocular viewing, as compared to the baseline binocular state. Although this result superficially resembles the Sprague effect, two patients benefited from right-monocular viewing whereas eleven patients showed no significant change in either right or left viewing conditions. The possible role of structures mediating interocular differences in target detection in cases of right hemisphere damage is discussed. It is suggested that even if the Sprague effect contributes to the salubrious influence of monocular viewing it is hardly the single factor involved. Show more

Keywords: Hemispatial neglect, Sprague effect, Monocular viewing, Rehabilitation, Substantia nigra pars reticulata, Superior col-liculi

DOI: 10.3233/RNN-1995-9202

Citation: Restorative Neurology and Neuroscience, vol. 9, no. 2, pp. 77-83, 1995

Authors: Ulenkate, Herman J.L.M. | Gispen, Willem-Hendrik | Jennekens, Frans G.I.

Article Type: Research Article

Abstract: The present study was undertaken to investigate the effect of Org2766 on the recovery of lesioned motor nerve fibres. The facial nerve of Wistar rats was crush lesioned and the process of recovery was assessed by functional and histological methods. Functional recovery was examined in two experiments and was assessed by quantifying blind the return of eyelid and whisker movements. No difference could be demonstrated between Org2766-treated and saline-treated groups of animals. The histological investigations involved quantifying the number of reinnervated motor endplates in the whisker muscle. On days 10 to 12 in male rats and on days 12 and …13 in female rats, there was no difference in reinnervation between the two treatment groups. It was concluded that with the methods used in this study, no significant effect of Org2766 on the axonal regeneration of motor nerve fibres could be established. Show more

Keywords: Neuropeptide, Axonal regeneration, Reinnervation, Facial nerve, Neuromuscular junction, Functional recovery

DOI: 10.3233/RNN-1995-9203

Citation: Restorative Neurology and Neuroscience, vol. 9, no. 2, pp. 85-91, 1995

Authors: Silverman, William F. | Solberg, Yoram | Pollack, Yaakov

Article Type: Research Article

Abstract: In the present study, we have examined the expression and distribution of the metabolic marker neuron-specific enolase (NSE) in solid-tissue transplants of fetal substantia nigra (SN) to the striatum of intact and 6-hydroxydopamine lesioned mature rats. Immunocytochemistry was applied to label NSE and tyrosine hydroxylase (TH) respectively. Cellular content of NSE is indicative of metabolic activity as well as synaptogenesis/maturation. Three months after implantation, the fetal grafts exhibited intensely TH-immunoreactive neurons, typically organized in elongated clusters, especially along the graft–host border and along blood vessels penetrating into the graft interior. Moderate to high metabolic activity as indicated by NSE immunoreactivity …was observed in neuronal perikarya, principally in non-TH immunoreactive areas. In contrast to these immunohistochemical findings, in situ hybridization for TH mRNA, carried out exclusively on grafts into the intact striatum, demonstrated DA cell bodies both at the graft–host interface and, significantly, throughout the graft interior. The number of transcripts per cell, moreover, did not differ significantly in these two locations. We propose that conditions at the graft–host border promote tissue-specific regulation of nigral DA neurons, and that this regulation occurs post-transcriptionally. Thus, DA neurons relatively distant from the host parenchyma are underregulated, resulting in a higher level of metabolic activity and an increased turnover of TH in the grafted neurons. Show more

Keywords: Dopamine, Messenger RNA, Substantia nigra, Neuron-specific enolase

DOI: 10.3233/RNN-1995-9204

Citation: Restorative Neurology and Neuroscience, vol. 9, no. 2, pp. 93-103, 1995

Authors: Sommer, Clemens | Bele, Sylvia | Gass, Peter | Kiessling, Marika

Article Type: Research Article

Abstract: N-Methyl-D-aspartate (NMDA) receptors are a major subfamily of glutamate receptors and thought to play a pivotal role in developmental plasticity and synaptogenesis, neuronal migration and differentiation. NMDA receptors have also been implicated in neuronal degeneration, as glutamate binding to the receptor initiates rapid excitotoxic signal transduction. Molecular cloning of cDNAs has yielded different NMDA receptor subtypes with an essential NR1 subunit associated with various modulatory NR2 subunits. The NR1 gene is expressed at high levels in virtually all brain structures, but to a distinctly higher extent in cortex than in striatum. Here we report on the development, maintenance and function …of glutamate receptors in intrastriatally located cortical grafts. Cortical primordia of rat fetuses (El4) were stereotactically grafted into the rostral striatum of adult recipient rats. Expression of NR1 mRNA was examined by in situ hybridization after post transplantation periods of 2, 6 and 12 months. Analysis of NR1 mRNA expression in grafts after a differentiation period of 2 months revealed equal levels compared to the intact neocortex of the host rats and that of rats with the same ontogenetic age. No downregulation of NR1 mRNA was seen 6 and 12 months after transplantation. To ensure normal function of NMDA receptors in grafts, we studied the effects of a blockade of receptor dependent gene expression, using Krox-24 as a reporter gene. In normal brain tissue, constitutive expression of KROX-24 protein is thought to be maintained by NMDA receptor mediated physiological synaptic activity and can be abolished by the non-competitive NMDA receptor antagonist MK-801. Immunostaining of KROX-24 protein was almost identical in grafts compared to the corresponding neocortex. This constitutive expression of KROX-24 could be abolished by treatment with MK-801. Thus, our data indicate normal development and long term persistence of glutamate receptors with intrinsic excitatory activity in transplants. Show more

Keywords: Transplantation, Plasticity, N-Methyl-D-aspartate receptor, KROX-24, Zif/268, MK-801, Immunocytochemistry, In situ hybridization

DOI: 10.3233/RNN-1995-9205

Citation: Restorative Neurology and Neuroscience, vol. 9, no. 2, pp. 105-111, 1995

Authors: Khoja, I. | Herranz, A.S. | Williams, J.R. | Cannon-Spoor, H.E. | Heim, R.C. | Freed, W.J. | Poltorak, M.

Article Type: Short Communication

Abstract: Localized lesions of the medial and lateral frontal cortex were used to study gliosis, neurofilament content and changes in synaptic density in the mouse striatum. Relationships between the sites of cortical lesions and the localization of changes in different regions of the striatum were examined after 3 and 12 weeks. Independent of the location of frontal cortex lesions, glial fibrillary acidic protein (GFAP) immunoreactivity was increased throughout the entire striatum after 3 weeks. Twelve weeks after lesioning, increases in GFAP were confined to the dorsomedial (DM) striatum following medial cortical lesions, and to the dorsolateral (DL) striatum following lateral cortical …lesions, suggesting persistent gliosis only in areas of striatal deafferentation. It appears, therefore, that the mechanisms which induce gliosis after short and long time periods are different. Show more

Keywords: Cortical lesion, Deafferentation, GFAP, Striatum, Astrocytes, Synapse

DOI: 10.3233/RNN-1995-9206

Citation: Restorative Neurology and Neuroscience, vol. 9, no. 2, pp. 113-119, 1995

Article Type: Research Article

DOI: 10.3233/RNN-1995-9207

Citation: Restorative Neurology and Neuroscience, vol. 9, no. 2, pp. 121-124, 1995