Restorative Neurology and Neuroscience - Volume 10, issue 2

Authors: Schmitt, Ulrich | Sabel, Bernhard A.

Article Type: Research Article

Abstract: Lack of trophic support after axonal injury leads to the degeneration of neurons. To study whether the application of trophic factor can improve functional recovery and retinal ganglion cell (RGC) survival after unilateral controlled optic nerve crush injury, we have now treated adult rats intraocularly (i.o.) with basic fibroblast growth factor (bFGF). To monitor visual deficits, rats were trained in a two-choice pattern discrimination test. Immediately after the crush, and on postoperative days 3 and 6, either 1.1 µg recombinant bFGF or phosphate buffered saline (PBS) was injected i.o. Sham-operated controls received intraocular injection of PBS or bFGF. Within the …first few days after the crush, all animals showed a loss of discrimination ability which was followed by a significant recovery within 2–3 weeks. Animals treated with bFGF had a significantly smaller initial deficit and thus recovered earlier compared to PBS controls. Retrograde RGC death was evaluated using retrograde HRP-tracing technique, but bFGF-treatment had no neuroprotective effect. Thus, the behavioral effects of bFGF could not be related to neuroprotection of RGCs and therefore other mechanisms may have to be considered. Show more

DOI: 10.3233/RNN-1996-10201

Citation: Restorative Neurology and Neuroscience, vol. 10, no. 2, pp. 61-68, 1996

Authors: Ninfali, Paolino | Cuppini, Carla | Marinoni, Silvia

Article Type: Research Article

Abstract: The effects of the rat sciatic nerve crush on the activities of glucose-6-phosphate dehydrogenase (G6PD), glutathione reductase (GR), glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT) were examined in regenerating nerve and in two reinnervating muscles: the slow twitch soleus and the fast twitch extensor digitorum longus (edl). The enzyme activities in the crushed side, were compared with the contralateral homologue tissues and basal values, determined in uncrushed animals. In the crushed side, the activity of G6PD, GR, GPX and CAT of the sciatic nerve and both muscles markedly increased in comparison with the uncrushed side. In the nerve …and in both muscles, SOD activity decreased at 13 days, then rose to values higher than normal, but the pattern of the crushed side was not significantly different from that of the uncrushed. In the uncrushed side, we observed a significant increase of nerve G6PD, GPX and CAT activities compared to basal values, while in both muscles, values fluctuated around the normal without any significant variation. The mechanism of these enzymatic changes is unknown, however our work suggests that: (i) during nerve regeneration, an oxidative stress occurs in nerve and muscle, which causes adaptive responses in antioxidant enzymes; (ii) the maximum antioxidant power is expressed during the period of synaptic retraction; (iii) G6PD and GR activities are synergistically modulated with GPX and CAT, while SOD activity appears independently regulated. Show more

Keywords: Glucose-6-phosphate dehydrogenase, Glutathione reductase, Antioxidant enzymes, Nerve regeneration, Muscle

DOI: 10.3233/RNN-1996-10202

Citation: Restorative Neurology and Neuroscience, vol. 10, no. 2, pp. 69-75, 1996

Authors: Carlson, Bruce M. | Billington, Lynn | Faulkner, John

Article Type: Research Article

Abstract: Denervated extensor digitorum longus (EDL) muscles in rats rapidly lose mass and contractile force. After two months of denervation, mass and maximum tetanic force have fallen to 31% and 2% of the values of contralateral control muscles. Our purpose was to determine if grafting a long-term denervated muscle into an innervated site provides an effective means of restoring its structure and function. EDL muscles that had been denervated for periods of 2–12 months were freely grafted into innervated sites of EDL muscles in 4-month inbred host animals. Contralateral normally innervated EDL muscles from the same donors were implanted into the …opposite legs of the same hosts. Two months after grafting, the muscles were removed and measurements were made in vitro of isometric contractile properties. The grafts were then prepared for morphological analysts. In all cases, the maximum forces generated by innervated grafts of denervated muscles were greater than those generated by denervated muscles. However, when compared with grafts of control muscles in the contralateral limb, grafts of previously denervated muscles showed a steady decline in structural and functional recovery corresponding to the time of previous denervation. The decline was especially pronounced for muscles denervated between 2 and 7 months prior to grafting. Grafts of 7-month denervated muscles were restored to only 17% of the maximum tetanic force of contralateral control grafts compared with 83% for grafts of 2-month denervated muscles. The longer a muscle had been denervated prior to grafting, the higher proportion of thin atrophic muscle fibers it contained. We conclude that grafting into an innervated site improves the mass and maximum force of a muscle over the denervated state, but the longer the period of prior denervation the poorer the recovery of the grafted muscles. Show more

Keywords: Denervation, Muscle, Rat, Grafting, Regeneration, Contractile properties

DOI: 10.3233/RNN-1996-10203

Citation: Restorative Neurology and Neuroscience, vol. 10, no. 2, pp. 77-84, 1996

Authors: van Meeteren, Nico L.U. | Brakkee, Jan H. | Biessels, Geert-Jan | Kappelle, Arnoud C. | Helders, Paul J.M. | Gispen, Willem H.

Article Type: Research Article

Abstract: The effect of moderate exercise training on acute and chronic neuropathy in two separate experiments was examined. Acute nerve dysfunction was induced by sciatic nerve crush lesion and chronic neuropathy by streptozotocin-induced diabetes mellitus (experimental diabetic neuropathy; EDN). Moderate exercise training was achieved by placing food and water, separately, at either end of a U-shaped tubular home cage (8 m). Recovery from the crush lesion and the development of EDN were monitored by evaluating the free walking pattern and nerve conduction velocity (NCV), respectively. In the acute neuropathy model, 24 days of exercise after the crush lesion resulted in an …enhanced return of motor function in the early phase of recovery (P < 0.01) and an increased sensory NCV after 250 days in the late phase (P < 0.001). Diabetic rats benefited from this exercise training by showing fewer signs of EDN, as evidenced by a superior motor function (toespreading, calculated from the free walking pattern; P < 0.05) and an improvement in both motor and sensory NCV (both P < 0.05). We conclude that moderate exercise training is effective in enhancing recovery from acute peripheral neuropathy and in ameliorating the consequences of experimental chronic neuropathy in diabetic rats. Show more

Keywords: Crush lesion, Diabetes mellitus, Diabetic neuropathy, Electrophysiology, Exercise training, Nerve, Rat, Regeneration

DOI: 10.3233/RNN-1996-10204

Citation: Restorative Neurology and Neuroscience, vol. 10, no. 2, pp. 85-93, 1996

Authors: Beazley, L.D. | Tennant, M. | Dunlop, S.A.

Article Type: Research Article

Abstract: The changes brought about in the severed optic nerve of an adult rat when the blood-optic nerve barrier was chronically broken down by the local application of a solution of mannitol is described. Axonal labelling indicated that axons did not regenerate across the lesion site, refuting the suggestion that breakdown of the blood-optic nerve barrier can stimulate axonal regeneration. However, we observed that blood vessels were dilated and, between the eye and lesion site, provided a substrate for regenerating axonal sprouts. We suggest that blood-borne agents may directly or indirectly influence the navigation of the growth cones of regrowing axons.

Keywords: Blood-optic nerve barrier, Mannitol, Optic nerve regeneration, Rat

DOI: 10.3233/RNN-1996-10205

Citation: Restorative Neurology and Neuroscience, vol. 10, no. 2, pp. 95-101, 1996

Authors: Borlongan, Cesario V. | Bjugstad, Kimberly B. | Stahl, Christine E. | Ross, Shajmil D. | Arendash, Gary W. | Cahill, David W. | Sanberg, Paul R.

Article Type: Research Article

Abstract: Neurobehavioral effects caused by the excitotoxin kainic acid (KA) have been characterized by convulsions including ‘wet dog shakes’ (WDS) with accompanying hippocampal degeneration in experimental animals. Accordingly, this model has been proposed for putative excitotoxin-mediated disorders, such as the temporal lobe epilepsy. There have been reports on age-dependent neurobehavioral effects of KA; however, little is known about possible correlations between neuropathology and behavioral responses to KA. The present study demonstrates that mature adult rats (12 months old) injected subcutaneously (s.c.) with KA (12 mg/kg) had severer damage to the hippocampal formation, i.e. CA3 region, compared with KA-treated young adult rats …(2 months old). The mature adult animals also exhibited an earlier onset of WDS, a significantly higher number of WDS (P > 0.01), and severer convulsions compared with young adult rats. These findings indicate a positive correlation between KA-induced hippocampal damage and behavioral responses in young and mature adult rats. Show more

Keywords: Kainic acid, Aging, N-methyl-D-aspartate, Wet dog shakes, Neurodegeneration, Hippocampus

DOI: 10.3233/RNN-1996-10206

Citation: Restorative Neurology and Neuroscience, vol. 10, no. 2, pp. 103-108, 1996

Article Type: Research Article

DOI: 10.3233/RNN-1996-10207

Citation: Restorative Neurology and Neuroscience, vol. 10, no. 2, pp. 109-120, 1996

Authors: Manev, H. | Uz, T. | Kharlamov, A. | Cagnoli, C.M. | Franceschini, D. | Giusti, P.

Article Type: Other

DOI: 10.3233/RNN-1996-10208

Citation: Restorative Neurology and Neuroscience, vol. 10, no. 2, pp. 121-121, 1996