Restorative Neurology and Neuroscience - Volume 6, issue 2

Authors: Szymankiewicz-Rak, Barbara | Mey, Jörg | Thanos, Solon

Article Type: Research Article

Abstract: Although glucocorticoids are commonly used for the treatment of optic nerve inflammations, little is known about direct effects of steroids on retinal nerve cells. In this study, the neuritogenic effect of prednisolone on retinal ganglion cells was investigated using retinal organ cultures derived from adult rats and embryonic chickens. The numbers of axons growing from retinal ganglion cells (RGC) in vitro were counted to measure the regenerative propensity at various corticosteroid concentrations. Prednisolone exerted a dose-dependent neuritogenic influence on RGC of either origin. The effect was highest at a concentration of 25 μg/ml culture medium, where axon numbers increased to …237% (rat) and 166% (chick) of the control values. This was highly significant (t-test: P < 0.01 and P < 0.005, respectively). High corticosteroid concentrations (>125 μg/ml) produced toxic effects, as revealed by low axon numbers as well as morphological alterations of the explants. Show more

Keywords: Retina, Axonal regeneration, Glucocorticoid, Rat, Chick

DOI: 10.3233/RNN-1994-6201

Citation: Restorative Neurology and Neuroscience, vol. 6, no. 2, pp. 83-87, 1994

Authors: Isono, Mitsuo | Braun, Dale | Poltorak, Maciej | Freed, William J.

Article Type: Research Article

Abstract: Immunological reactions after intracerebroventricular syn-, allo- and xenogenic transplantation of adrenal medulla were investigated histologically. In xenografts only, T cell infiltration and graft rejection were observed. Syngrafts and allografts were not rejected and were not infiltrated by T cells, although expression of MHC class II antigen was observed at all survival times. Major histocompatibility complex (MHC) class I immunoreactivity was strongly expressed in adrenal cortex syngrafts, which could play a role in the rejection of grafts containing mixed cell populations. The survival of chromaffin cells in allografts was decreased as compared to syngrafts, and there were fewer allograft animals with …large numbers of surviving chromaffin cells. There was some increased cellularity (microglia and macrophages) in allografts even though no T cell infiltration was found. Therefore, it appears that this limited survival of intracerebral adrenal medulla allografts is not due to T cell-mediated graft rejection. Show more

Keywords: Adrenal medulla graft, Immunological reaction, Graft rejection, Xenograft

DOI: 10.3233/RNN-1994-6202

Citation: Restorative Neurology and Neuroscience, vol. 6, no. 2, pp. 89-95, 1994

Authors: Ząbek, M. | Mazurowski, W. | Dymecki, J. | Stelmachów, J. | Zawada, E.

Article Type: Research Article

Abstract: In three parkinsonian patients ages 48, 53, and 50, human fetal dopaminergic cells taken from the ventral part of mesencephalon of 11–12-week-old fetuses were implanted into the head of caudate nucleus. The operation was carried out with a specially designed device to enable safe and precise graft implantation. All patients had been suffering from severe Parkinson's disease for about 10–15 years (stage 4/5 according to Hoehn and Yahr scale) with bradykinesia, rigidity and tremor as the main symptoms. Long-lasting L-dopa therapy resulted in side effects with ON/OFF syndrome and dyskinesias. A detailed clinical examination was performed before and every 3 …months after the operation according to the CAPIT battery of standarized tests. The patients were under post-operational observation lasting 30, 20 and 12 months, respectively. Improvement was observed in all patients starting between 3 and 6 months after operation and is still sustained. Significant increases in movement speed for repeated pronation-supination, finger dexterity and foot lifting tests were found. The speed of walking also increased with decreased rigidity. The OFF phase during the day is of shorter duration and less severe; dyskinesias are markedly reduced. Our results indicate that fetal grafting seems to be a valuable experimental approach towards the treatment of selected parkinsonian patients. Show more

Keywords: Parkinson's disease, Neurotransplantation, Human fetal tissue, Postoperative result

DOI: 10.3233/RNN-1994-6203

Citation: Restorative Neurology and Neuroscience, vol. 6, no. 2, pp. 97-106, 1994

Authors: Shohami, E. | Novikov, M. | Horowitz, M.

Article Type: Research Article

Abstract: Closed head injury leads to delayed tissue-edema, necrosis and impaired neurological function. In the present study the effect of chronic exposure to heat on the outcome of head injury in rats was investigated. Rats were held at ambient temperature of 24°C (CON) or 34°C (heat acclimated, ACC) for one month, before induction of trauma. Injury was induced by a weight drop device, falling over the left cerebral hemisphere. Twenty-four or 48 h later the rats were sacrificed and their brains removed for evaluation of edema (specific gravity or water content). Blood-brain barrier integrity (Evans blue extravasation) was evaluated 4 h …after injury. One, 24 and 48 h after injury the rats were evaluated by a set of criteria which yields their clinical status (Neurological Severity Score – NSS). Forty-eight hours after trauma specific gravity of the contused hemispheres was 1.0389 ± 0.0019 and 1.0364 ± 0.0007 (P < 0.01) and water content 81.44 ± 1.28 and 84.17 ± 1.03% (P < 0.001), for ACC and CON rats, respectively. Lower degree of edema was also evident at 24 h suggesting slower rate of edema formation in ACC rats. Evans blue uptake by the contused hemisphere was 315 ± 61 and 50 ± 23 ng/g tissue in the CON and ACC rats, respectively (P < 0.001). Clinical recovery of the ACC rats was significantly better (P < 0.001) than that of the matched controls as exhibited at 48 h by median NSS values of: 10.8 (range 6–16) and 5 (range 4–6) for CON and ACC, respectively. Based on the present results we suggest that heat acclimation offers protection to rats subjected to head trauma. Show more

Keywords: BBB, Head trauma, Heat acclimation, Brain edema

DOI: 10.3233/RNN-1994-6204

Citation: Restorative Neurology and Neuroscience, vol. 6, no. 2, pp. 107-112, 1994

Authors: Pyapali, G.K. | Turner, D.A. | Madison, R.D.

Article Type: Research Article

Abstract: Host brain receptivity to fetal hippocampal grafts was investigated following transplantation into unilateral kainic acid (KA) lesions of adult rat hippocampus. E18–E19 hippocampal cell suspensions were labeled with rhodamine dextran amine and transplanted bilaterally into hosts at various times following the KA-lesion. After one to three and one half months survival the grafts (contained within host hippocampal slices) were analyzed using intracellular electrophysiological techniques. A nonparametric graft index was developed which assessed the overall size and distribution of the graft. Using this grading system graft development was noted to be significantly enhanced for grafts placed into hosts with KA lesions …at either 2–4 days or 11–12 days following the lesion, compared to grafts placed at either 6–7 days or 27–33 days after the lesion. Also, grafts implanted at delays of either 14–16 or 28–33 days appeared to have fewer surviving cells but were more dispersed within the host brain than grafts at shorter post-lesion implant times. Synaptic responses to host stimulation were noted in most grafts. Intracellular staining of transplanted neurons showed considerable development of cell processes but atypical pyramidal cell morphology and ectopic location; numerous axons traveled into the host tissue. The time course of lesion-induced host receptivity appeared to significantly influence graft development and maturation. In this study graft survival was partially independent from cell migration. This differential effect may be due to various aspects of host brain receptivity, which in turn is influenced by the delay between the host brain lesion and grafting. Show more

Keywords: Kainic acid lesion, Post-lesion delay, Fetal neural graft, Fluorescent label, Hippocampus, Neuronal structure, Physiological recording

DOI: 10.3233/RNN-1994-6205

Citation: Restorative Neurology and Neuroscience, vol. 6, no. 2, pp. 113-126, 1994

Authors: Bonheur, J.L. | Laev, H. | Vorwerk, C. | Karpiak, S.E.

Article Type: Research Article

Abstract: GM1 ganglioside (monosialoganglioside) is a significant endogenous component of central nervous system (CNS) cellular membranes, thereby contributing to the membranes' integrity and function. Exogenous gangliosides have been shown to be incorporated into plasma membranes and can exert neuroprotective effects on damaged neuronal tissue(s). An in vitro method of physical injury (trauma) previously described which used cultures derived from fetal mouse spinal cord [38] was adapted for these studies in order for us to assess GMl's neuroprotective efficacy. Injury was induced by uniformly crosshatching the spinal cell cultures with a 1 mm plastic pipette tip. The extent of injury and the …effects of GM1 ganglioside posttreatment (80 μM) was assessed after 48 h by measuring lactate dehydrogenase (LDH) released and by observing changes in the plasma membrane surface distribution of endogenous GM1 using cholera toxin/antitoxin/fluorescent antibody immunohistochemistry. A gradient of injury, from the zone of maximum injury to partially traumatized or non-injured areas, was seen using immunohistochemistry. The primary injury zone in this gradient was characterized by areas of swollen or dead cells and abnormal or degenerating cell processes. At further distances, cells were observed to be nearly normal, with intact fibers. This gradient of injury may reflect proximate (at the locus of trauma) and distant effects of the release of neurotoxic levels of endogenous glutamate (Glu) and other excitatory amino acids. Ganglioside GM1 treatment resulted in a significantly reduced (>75%) release of LDH as well as enhanced cell and process integrity indicative of reduced tissue injury. These initial results indicate that GMl's previously documented neuroprotective effects using neuronal culture systems can be generalized to injured spinal cells in vitro wherein there is evidence for preservation (rescue) of cellular plasma membranes after injury as reflected by reduced cell loss, swelling, and process degeneration, as well as decreased LDH release. Show more

Keywords: Spinal cord, Physical trauma, GM1, Ganglioside, Immunohistochemistry

DOI: 10.3233/RNN-1994-6206

Citation: Restorative Neurology and Neuroscience, vol. 6, no. 2, pp. 127-133, 1994

Authors: Le Sauter, Joseph | Silver, Rae

Article Type: Research Article

Abstract: It is widely accepted that the suprachiasmatic nuclei (SCN) of the hypothalamus serve as biological pacemakers, organizing daily activities. However some circadian rhythms are controlled by extra-SCN structures. Transplantation of fetal donor SCN in SCN-lesioned rodents induces recovery of rhythmic locomotor and drinking activities. Such grafts do not however, restore appropriate gonadal responses to photoperiodic stimuli. It is not known whether other behavioral rhythms are restored by fetal tissue grafts, or whether various responses are restored simultaneously. In the present study, we established that circadian rhythms of gnawing behavior are abolished following SCN lesions. Next, we measured both gnawing and …wheel-running activity in SCN-lesioned hamsters following transplantation of fetal hypothalamic grafts containing the SCN. The results indicate that such grafts restore circadian rhythms of gnawing behavior, and that gnawing and wheel-running rhythms re-emerge at about the same time. Show more

Keywords: Gnawing, Hamster, SCN lesion, SCN graft, Circadian

DOI: 10.3233/RNN-1994-6207

Citation: Restorative Neurology and Neuroscience, vol. 6, no. 2, pp. 135-143, 1994

Authors: Schmidt-Kastner, R. | Gocht, A. | Meller, D. | Wietasch, K. | Weigel, H. | Eysel, U.T.

Article Type: Research Article

Abstract: Immunohistochemical staining of myelin basic protein (MBP) was followed during axonal degeneration of rat retinal fibers within the first 3 weeks after injury. Wallerian degeneration of rat retinal fibers was elicited by unilateral transection or crush injury of optic nerve. MBP-labelled fibers in central retinal pathways and visual nuclei showed sequential changes of the myelin sheath, such as swelling at 1–2 days post lesion (dpi), granular staining at 4–8 dpi, and granular debris formation at 21 dpi. Consequently, immunostaining for MBP could be used to identify early stages of degenerating myelin and persisting myelin debris which is known to contain …neurite growth inhibitors. Show more

Keywords: Retinal fiber, Axon, Wallerian degeneration, Myelin basic protein, Immunohistochemistry, Rat

DOI: 10.3233/RNN-1994-6208

Citation: Restorative Neurology and Neuroscience, vol. 6, no. 2, pp. 145-149, 1994

Authors: Navarro, Xavier | Butí, Miquel | Verdú, Enrique

Article Type: Research Article

Abstract: This study evaluates the degree of autotomy induced by anesthesia dolorosa after transection of the sciatic and saphenous nerves in four different strains of mice, and the effectiveness of amitriptyline administration in two of them. The self-mutilating lesions were assessed by means of an autotomy score for one month after denervation. The onset of lesions generally occurred during the first week, starting in the nails and progressing proximally. Autotomy behavior developed differently in the mouse strains studied, involving 88% of the paw areas in OF1 mice, 61% in Balb-C, 35% in NMRI, and 15% in B6CBAF1. Two selected strains, OF1 …and NMRI, were treated with amitriptyline (8 mg/kg/day, p.o.) from different intervals pre-operation. Administration starting 14 days before nerve lesion was the most effective treatment schedule for reducing autotomy in both strains. Show more

Keywords: Amitriptyline, Antidepressant, Autotomy, Deafferentation pain, Peripheral nerve, Nerve regeneration

DOI: 10.3233/RNN-1994-6209

Citation: Restorative Neurology and Neuroscience, vol. 6, no. 2, pp. 151-157, 1994

Authors: Fulop, Zoltan

Article Type: Book Review

DOI: 10.3233/RNN-1994-6210

Citation: Restorative Neurology and Neuroscience, vol. 6, no. 2, pp. 159-159, 1994