Restorative Neurology and Neuroscience - Volume 14, issue 1

Authors: Graczyk, Piotr P.

Article Type: Research Article

Abstract: Contribution of apoptotic mechanisms to neurodegeneration is an emerging concept. Caspases which are activated during apoptotic cell death may serve as an attractive target of pharmacological intervention. Caspase inhibitors include proteins, peptides, peptidomimetics and various small molecules. Peptide conjugates with quinones, epoxyquinones and epoxyquinols which constitute new types of pharmaeophores exhibit submicromolar activity against caspase-3 and show moderate neuroprotective effects on neuronal cells. Peptide-derived inhibitors may suffer from insufficient cell membrane …permeability. However, double ester-type prodrugs may offer an option to transport a peptide-like inhibitor across the cell membrane. These developments may lead to identification of novel neuroprotective drugs. Show more

Keywords: neurodegeneration, apoptosis, caspase inhibitors, quinones, epoxyquinones, epoxyquinols, prodrugs

Citation: Restorative Neurology and Neuroscience, vol. 14, no. 1, pp. 1-23, 1999

Authors: Seitz, Rüdiger J. | Knorr, Uwe | Azari, Nina P. | Herzog, Hans | Freund, Hans-Joachim

Article Type: Research Article

Abstract: Recovery of finger movements after hemiparetic stroke has been shown to involve sensorimotor brain areas in perilesional and remote locations. Hand use, however, critically depends on visual guidance in such patients with stroke lesions in the middle cerebral artery territory. Using regional cerebral blood flow measurements, we wished to identify interrelated brain areas that are engaged in relation to manual activity in seven patients after their first hemiparetic brain infarction. During the blind-folded performance of sequential …finger movements, the patients differed significantly from healthy controls (n = 7) by the recruitment of a predominantly contralesional network involving visual cortical areas, prefrontal cortex, thalamus, hippocampus, and cerebellum. Greater expression of this cortical-subcortical network correlated with a more severe sensorimotor deficit in the acute stage after stroke reflecting its role for post-stroke recovery. Patients also differed from controls on a lesion-related pattern expressed during rest. A third differentiating pattern involved the ipsilesional supplementary motor area and the contralesional premotor cortex. Our results suggest that post-stroke recovery form impaired sensorimotor integration utilizes crossmodal plasticity of a visual network. Show more

Keywords: stroke, hemiparesis, sensorimotor integration, motor recovery, plasticity, functional imaging

Citation: Restorative Neurology and Neuroscience, vol. 14, no. 1, pp. 25-33, 1999

Authors: Wallace, Amy E. | Kline, Anthony E. | Montañez, Sylvia | Hernandez, Theresa D.

Article Type: Research Article

Abstract: GABAergic drugs can positively or negatively influence recovery of neurobehavioral function following brain injury. Direct potentiation of GABA-mediated inhibition at the post-synaptic receptor (i.e., via GABA, muscimol, diazepam, phenobarbital) after brain damage has been associated with impaired functional recovery. What remains unclear, however, is whether the mechanism of action by which GABA is augmented contributes to a drug's impact on the recovery process. Vigabatrin, a novel anti-convulsant that inhibits GABA-transaminase, was administered …chronically after unilateral anteromedial cortex lesions and recovery from somatosensory deficits assessed. In contrast to the direct GABA receptor agonists, vigabatrin did not adversely impact (i.e., was neutral) recovery from neurobehavioral deficits at any of the anti-convulsant doses tested. Measurable secondary drug effects like sedation and hypothermia diminished over time and were reversible upon drug discontinuation. These results suggest that the degree to which a GABAergic agent impacts the recovery process after brain injury is dependent on the drug's mechanism of action. Show more

Keywords: GABA, anteromedial cortex lesion, somatosensory asymmetry, rat, behavior, pharmacotherapy

Citation: Restorative Neurology and Neuroscience, vol. 14, no. 1, pp. 35-45, 1999

Authors: Vorwerk, Christian K. | Bonheur, Jennifer | Kreutz, Michael R. | Dreyer, Evan B. | Laev, Heljo

Article Type: Research Article

Abstract: Injury of the nervous system initiates a cascade of signal transduction including a rise in extracellular glutamate which leads to subsequent secondary neuronal loss. Excitotoxicity is known to play a crucial role in cell death spinal cord trauma. Gangliosides, particularly monosialogangliosides (GM1), are protective against various neurological insults, including excitotoxicity. Gangliosides may improve outcome following human spinal cord injury in humans. To further explore the relationship between excitotoxicity and GM1, dissociated murine …spinal cord preparations were exposed to glutamate (0.5 mM) with the subsequent administration of GM1 (80 µM) at 8 and 13 days in culture. The addition of GM1 30 minutes after exposure to glumatate significantly reduced neuronal damage and preserved membrane structure and integrity. These results demonstrate that post-treatment with GM1 gangliosides after glutamate-induced excitotoxicity is effective in protecting spinal cord neurons. Show more

Keywords: ganglioside, glutamate, spinal cord, in vitro, LDH, immunohistochemistry

Citation: Restorative Neurology and Neuroscience, vol. 14, no. 1, pp. 47-51, 1999

Authors: Moriarty, Loren J. | Borgens, Richard B.

Article Type: Research Article

Abstract: Macrophages are implicated to play a substantive role in the acute inflammatory reaction to CNS insult in the delayed progressive secondary damage to parenchyma, espacially myelin. When placed in an electrical field in vitro, macrophages show directed pseudopodial extensions and migrate towards the positive pole (anode). We have evaluated if ED1 positive macrophage accumulations in rat spinal cord injuries were affected by the applied extracellular voltage, comparing their numbers to a sham treated group. Our …hypothesis was that the applied voltage may reduce the concentration of phagocytes in the central injury and thus reduce the level of secondary damage produced by them. The applied voltage gradient did not alter the number or density of macrophage accumulations in the three week lesion, nor is there any difference in the degree of cavitation between control and experimental groups. Show more

Keywords: spinal injury, macrophage, electric field, secondary injury, inflammatory reaction

Citation: Restorative Neurology and Neuroscience, vol. 14, no. 1, pp. 53-64, 1999

Authors: Rodríguez, Francisco J. | Gómez, Nuria | Labrador, Rafael O. | Butí, Miquel | Ceballos, Dolores | Cuadras, Jordi | Verdú, Enrique | Navarro, Xavier

Article Type: Research Article

Abstract: We compared regeneration and reinnervation of target organs after sciatic nerve resection and repair with silicone tubes filled with saline solution or with a peroneal nerve segment as a nerve transplant versus an autologous sciatic nerve graft leaving either 4 mm or 6 mm gaps. The aims of this study were to evaluate the effects of predegeneration and donor immunogenicity of nerve transplants. Functional reinnervation was assessed by noninvasive methods to determine recovery of sweating, sensory and motor functions in the hindpaw after three months postoperation for 4 mm and four months postoperation for 6 mm gap groups. Morphometrical analysis …of the regenerated nerve were performed at the end of the follow-up. The group with an autograft achieved faster and higher levels of reinnervation for the four functions tested than any of the groups repaired by tubulization. The introduction of a small nerve transplant improved regeneration and reinnervation with respect to a saline solution filled tube slightly with a 4 mm gap, but significantly with a 6 mm long gap. The beneficial effects of the nerve transplant were significantly increased when it was predegenerated, while disappearing when its cellular component was eliminated by repeated freezing. The immunogenicity of the nerve transplant dramatically affected nerve regeneration, as it was impeded by an heterologous transplant in the tube. In summary, the use of silicone chambers with an autologous predegenerated nerve transplant may be an alternative for repairing long gaps in injured nerves, approaching the level of success of an ideal autologous nerve graft. Show more

Keywords: nerve regeneration, reinnervation, tube repair, nerve transplant, degeneration, sciatic nerve

Citation: Restorative Neurology and Neuroscience, vol. 14, no. 1, pp. 65-79, 1999

Authors: Kasten, Erich | Tausch, Nicole

Article Type: Book Review

Citation: Restorative Neurology and Neuroscience, vol. 14, no. 1, pp. 81-81, 1999