Restorative Neurology and Neuroscience - Volume 6, issue 4

Authors: Hayes, K.C.

Article Type: Review Article

Abstract: Demyelination of axons within the spinal cord represents a significant component of the pathology of contusive and compressive spinal cord injury (SCI) and the associated conduction deficits most probably contribute to the paralysis and sensory loss experienced by SCI patients. 4-Aminopyridine (4-AP) is a potassium (K+ ) channel blocking agent that has been shown capable of restoring conduction across demyelinated internodes in neurons of the spinal cord. Recent clinical trials of 4-AP provide evidence that limited and transient neurological gain may be derived by some SCI patients with longstanding injury. The present review traces the historical development of 4-AP, describes …the mechanism of action and rationale for use in SCI, and provides an overview of the clinical trials conducted to date. The early trials give rise to optimism that pharmaceutical management of conduction deficits may have a role to play in restoring neurological function in some patients with SCI. Show more

Keywords: Spinal cord injury, 4-Aminopyridine, Demyelination

DOI: 10.3233/RNN-1994-6401

Citation: Restorative Neurology and Neuroscience, vol. 6, no. 4, pp. 259-270, 1994

Authors: Kappelle, A.C. | Biessels, G. | , T. | Van Buren, | Brakkee, J.H. | Gispen, W.H.

Article Type: Research Article

Abstract: Nimodipine, a Ca2+ antagonist of the dihydropyridine type, is known to display a variety of neuropharmacological effects including facilitation of functional recovery following a crush of the sciatic nerve in the rat. In the present study, we investigated the effect of nimodipine, nifedipine (another Ca2+ antagonist with a lesser penetration in neural parenchyma) and Bay K 8644 (a Ca2+ agonist) treatment following a crush of the major caudal nerve. The caudal nerve crush model was used because this model provided the opportunity for longitudinal evaluation of nerve repair. Recovery of sensory function was tested by vocal reaction …following local stimulation with a small electric current. The results suggest that nimodipine (20 mg/kg) both enhances the initial sprouting response and exerts an effect on the outgrowth rate of newly developed sprouts. Neither nifedipine (20 mg/kg) nor Bay K 8644 (0.5 mg/kg) had any influence on the recovery of nerve function. Furthermore, it was demonstrated that nimodipine, nifedipine and Bay K 8644 had no influence on nerve conduction velocity of the non-injured sciatic nerve indicating that there was no general beneficial effect of these agents on the peripheral nerve. Show more

Keywords: Crush lesion, Nerve, Ca2+ antagonist, Ca2+ agonist, Regeneration, Rat

DOI: 10.3233/RNN-1994-6402

Citation: Restorative Neurology and Neuroscience, vol. 6, no. 4, pp. 271-276, 1994

Authors: Pécot-Dechavassine, Monique | Horvat, Jean-Claude | Mira, Jean-Claude | Ye, Jian Hui

Article Type: Research Article

Abstract: In previous ‘short-term’ (2 to 7 months) experiments, we had demonstrated, in the adult rat, that motoneurons of the injured cervical spinal cord could extend lengthy axons into an autologous peripheral nerve segment which was connected to a nearby denervated skeletal muscle. In addition, we had shown that new functional motor endplates were formed by these axons both at the original sites of innervation and at ectopic locations of the denervated muscle. This substitution motor system, although quite functional, was anatomically very different from the original model of innervation in the intact animal, relating to its motoneuronal pool, the course …of its motor axons and the sites of terminal innervation. The present ‘long-term’ (11 to 21 months) experiments demonstrate the anatomical and functional permanency of the new motor circuitry, despite a lack of strict specificity in the new neuromuscular connections. However, some minor modifications or adjustments were observed with time: (i) the maintenance of functional ectopic endplates could be consistently demonstrated, while functional reinnervated endplates at the initial sites of innervation were rare or even lacking; (ii) there was a definitive withdrawal of all non target-specific regenerated axons from the vicinity of the muscle. It is now necessary to address the question to what extent this substitution motor system is actually controlled by central and/or peripheral inputs. Show more

Keywords: Adult rat, Spinal cord reconstruction, Motoneuron, Axonal regeneration, Peripheral nerve autograft, Motor endplate, Retrograde axonal tracing, Electrophysiological recording

DOI: 10.3233/RNN-1994-6403

Citation: Restorative Neurology and Neuroscience, vol. 6, no. 4, pp. 277-286, 1994

Authors: Gold, Bruce G. | Storm-Dickerson, Toni | Austin, Daniel R.

Article Type: Research Article

Abstract: Regeneration of peripheral nerve fibers over long distances often requires extended periods of convalescence. Loss to society can be measured in terms of increased health care costs, decreased productivity and, in the case of job-related injuries, larger workers' compensation claims. The availability of drugs to increase axonal regeneration would be beneficial not only to patients but also to society in general by decreasing these costs. In the present paper, we present our initial studies on the regenerative effects of the new immunosuppressive agent FK506. Rats given a sciatic nerve crush (axotomy) received daily subcutaneous injections of FK506 (1.0 mg/kg); axotomized …control animals received saline. Clinical signs of recovery in the hind feet were manifested two days earlier in FK506-treated than in saline-treated animals; movement in the toes, and walking on the hind feet and toes were observed at 16 and 17 days, respectively, in saline-treated rats and at 14 and 15 days, respectively, in FK506-treated rats. Measurement of interdigit distances in the hind feet at 18 days following axotomy showed a return toward normal position of the toes (increased interdigit distances) during walking in FK506-treated rats. Light and electron microscopy performed at 18 days following axotomy confirmed the clinical appearance of increased functional recovery in FK506-treated rats. Distal to the crush site, the sciatic nerve and its terminal branches from FK506-treated animals contained more myelinated fibers compared to saline-treated animals; in the soleus nerve, the numbers of myelinated axons was increased 2.75-fold. Taken together, the present results suggest that FK506 enhances recovery of function in the rat by increasing the rate of axonal regeneration following a sciatic nerve crush. Show more

Keywords: Axotomy, Calcineurin, Calmodulin, FK506, GAP-43, Immunosuppressant, Regeneration, Sciatic nerve

DOI: 10.3233/RNN-1994-6404

Citation: Restorative Neurology and Neuroscience, vol. 6, no. 4, pp. 287-296, 1994

Authors: Nakamura, S.

Article Type: Research Article

Abstract: The antagonizing effect of the β-adrenoceptor antagonist propranolol (PRP) on the desipramine (DMI)-induced regeneration of brain noradrenergic fibers was examined. The symmetrical sites of the rat frontal cortex were pretreated with 6-hydroxydopamine (6-OHDA). Then, the same cortical site of one hemisphere was infused with DMI, while the corresponding site of the other hemisphere was infused with DMI (1 mM) plus PRP (1 mM). The DMI-induced axonal regeneration was attenuated by PRP. This finding suggests that activation of β-adrenoceptors is involved at least in part in the regeneration of brain noradrenergic axons.

Keywords: Antidepressant, Desipramine, Beta-adrenoceptor, Propranolol, Noradrenergic axon, Axonal regeneration

DOI: 10.3233/RNN-1994-6405

Citation: Restorative Neurology and Neuroscience, vol. 6, no. 4, pp. 297-300, 1994

Authors: Murray, Marion | Murphy, Carol A. | Ross, L.L. | Haun, Forrest

Article Type: Research Article

Abstract: The fasciculus retroflexus (FR) is the major pathway by which the medial and lateral habenular nuclei project to the interpeduncular nucleus (IPN) and ventral tegmentum. Recent work has suggested that the habenula-interpeduncular system may be involved in the regulation of states of arousal. Bilateral FR lesions have been shown to disrupt chronically, and habenula transplants have been shown to restore normal sleep patterns in rats [J. NeuroscL, 12 (1992) 3282–3290]. In this study, we examined whether FR lesions and habenula cell transplants would also modify chronically the circulating plasma levels of the stress-related hormones, norepinephrine (NE), epinephrine (EPI) and corticosterone. …When plasma samples were obtained via retro-orbital eye-bleed during anesthesia, animals with FR lesions had significantly increased levels of plasma NE, EPI and corticosterone 2–3 months postoperatively compared to unoperated controls. Transplants of embryonic habenula cells placed near the denervated IPN in FR-lesioned animals restored levels of NE and EPI to normal, but did not attenuate elevated corticosterone levels. When plasma samples were obtained in conscious animals via indwelling arterial cannulae, FR-lesioned rats likewise exhibited increased basal levels of corticosterone but plasma levels of catecholamines were similar to those of unoperated controls. Differences in our results obtained using the two methods of blood sampling may be explained by the effects of anesthesia and stress associated with the eye-bleed method. Thus, the effect of FR lesions in increasing plasma levels of catecholamines may not reflect a difference in basal hormone levels, but a heightened sympathetic adrenomedullary response to stress. While these results indicate that the integrity of the habenular efferent pathway is important in modulating circulating levels of hormones associated with the stress response, two separate mechanisms appear to control its interactions with sympathetic-adrenal medullary and adrenocortical pathways. Show more

Keywords: Habenula, Interpeduncular nucleus, Transplant, Norepinephrine, Epinephrine, Corticosterone

DOI: 10.3233/RNN-1994-6406

Citation: Restorative Neurology and Neuroscience, vol. 6, no. 4, pp. 301-307, 1994

Authors: Kohmura, Eiji | Yuguchi, Takamichi | Yamada, Kazuo | Sakaguchi, Tateo | Hayakawa, Toru

Article Type: Research Article

Abstract: Retrograde degeneration of thalamic neurons after cortical ablation has long been recognized. Neuronal loss following axotomy eliminates the possibility of regeneration and might prevent the recovery from axonal injury in patients with brain trauma. We investigated whether CS23, a stable recombinant variant of human basic fibroblast growth factor (bFGF), could protect neurons from retrograde degeneration. Four weeks after ablation of the somatosensory cortex in young female rats, there was extensive neuronal degeneration and loss in the lateral ventro-posterior nucleus (VPL) of the ipsilateral thalamus. When Gelfoam soaked in bFGF(CS23) (1 μg/0.l ml) was applied topically at the time of surgery, …this neuronal degeneration in the VPL was markedly reduced and macroscopic atrophy of the lateral and medial ventroposterior nucleus (VPL + VPM) was significantly reduced. In contrast, application of bFGF at three days after surgery failed to prevent retrograde degeneration. These resuts indicate that bFGF can prevent thalamic atrophy after ablation of the somatosensory cortex and that administration of bFGF is only effective in the very early period after brain injury. Show more

Keywords: Fibroblast growth factor, Injury, Neuron, Thalamic degeneration

DOI: 10.3233/RNN-1994-6407

Citation: Restorative Neurology and Neuroscience, vol. 6, no. 4, pp. 309-316, 1994

Authors: Danielsen, Nils | Johansson, Bengt R. | Dahlin, Lars B.

Article Type: Research Article

Abstract: The silicone chamber model for nerve regeneration is suitable to test the effects of exogenous agents or surgical manipulations on nerve regeneration. The total 16-day regeneration period used in this model makes it possible to analyze the effects of certain manipulations on the sequential advancement of the individual cellular components (circumferential perineurial-like cells, vessels, Schwann cells, axons, and myelin) into the chamber fibrin matrix. In the present study we compared the effects on cellular migration of a 7 day delayed chamber repair vs. chamber repair immediately after transection (control chambers) of the rat sciatic nerve. Regeneration was evaluated with light …and electron microscopic techniques. Chambers implanted after a delay of 7 days had a statistically significant more advanced migration of vessels, Schwann cells, and axons from the proximal nerve stump and also a significantly increased vascular density as compared to control chambers. We conclude that a 7 day delayed nerve repair stimulates nerve regeneration in this specific silicone chamber model. Show more

Keywords: Nerve regeneration, Vascularization, Silicone chamber, Rat sciatic nerve, Nerve repair, Schwann cell

DOI: 10.3233/RNN-1994-6408

Citation: Restorative Neurology and Neuroscience, vol. 6, no. 4, pp. 317-322, 1994

Article Type: Research Article

DOI: 10.3233/RNN-1994-6409

Citation: Restorative Neurology and Neuroscience, vol. 6, no. 4, pp. 323-339, 1994