Restorative Neurology and Neuroscience - Volume 15, issue 1

Authors: Stichel, Christine C. | Lausberg, Friederike | Hermanns, Susanne | Müller, Hans Werner

Article Type: Research Article

Abstract: After injury of the adult mammalian CNS axonal regeneration across or around the lesion scar is negligible. Previously, we have shown that the lesion-induced basal membrane (BM) within the lesion center participates in a growth barrier for axon regeneration and that its reduction by means of pharmacological or immunochemical treatment is a prerequisite and sufficient condition for regrowing axons to cross the lesion site. The present study was designed to further investigate this observation by analyzing the effect of a delayed treatment on the regeneration of both subacutely and chronically lesioned axons. Adult rats underwent unilateral transection of the postcommissural …fornix. At one to five days after transection one group of animals received a local injection of 2, 2'-dipyridyl (DPY), an inhibitor of collagen triple helix formation and synthesis. Another group received a second transection within the former lesion site followed by an immediate DPY-injection at five days or 4 weeks after transection. Six weeks after the last surgery BM deposition and axonal regeneration were analysed using immunocytochemical methods. A local injection of DPY clearly reduced the lesion-induced BM deposition when applied within the first 3 days after transection. Under these conditions regrowing axons still crossed the former impermeable lesion site and regenerated within their normal pathway up to their former target, the mammillary body. However, in late subacute (5 d) and chronic stages (4 w) the double transection+injection paradigm failed to reduce BM deposition and, in consequence, also to induce axonal regeneration. These results demonstrate the potential of the collagen IV-reducing strategy to promote axonal regeneration across the lesion scar not only in acute but also in early subacute traumatic injuries. Show more

Keywords: injury, scar, barrier, collagen IV, basal membrane

Citation: Restorative Neurology and Neuroscience, vol. 15, no. 1, pp. 1-15, 1999

Authors: Accioli-de-Vaconcellos, Zulmar Antônio | Kassar-Duchossoy, Lina | Mira, Jean-Claude

Article Type: Research Article

Abstract: The authors used different kinds of peripheral nerve grafts to reconstruct a terminal branch of the brachial plexus (the median nerve) gap of adult Sprague-Dawley rats, including fresh or frozen autografts and allografts from Norway rats. They also performed acellular allograft repopulation by autogenous Schwann cells, to improve the environment for nerve regeneration. Three, six, nine and twelve months after grafting, rats underwent histological assessment (muscle, nerve and spinal cord) and simple functional assessment by …the grasping test. Initially, the functional recovery of frozen grafts was lower than fresh graft recovery, but twelve months after surgery it was similar for both types of graft. Show more

Keywords: brachial plexus, peripheral nerve, frozen nerves, allografts, schwann cells, rats

Citation: Restorative Neurology and Neuroscience, vol. 15, no. 1, pp. 17-24, 1999

Authors: Lescaudron, Laurent | Stein, Donald G.

Article Type: Research Article

Abstract: Alzheimer's disease is a progressive dementia associated with cholinergic cell loss in the nucleus of Meynert that induces deficiencies in cholinergic neurotransmission in the neocortex. The nucleus basalis magnocellularis (NBM) is the rodent homologue to the nucleus of Meynert in humans. In this study, we examined the effects of GM1 ganglioside, a neuroprotective agent, on morphological and functional recovery after electrolytic or ibotenic acid lesions of the NBM. In animals, GM1 ganglioside …has been shown to reduce some of the behavioral deficits that follow Central Nervous System lesions. Electrolytic or ibotenic acid lesions produced deficits in passive avoidance learning, as assessed by the number of trails taken to acquire the avoidance response. Only the electrolytic lesions impaired spatial memory in the Morris Water Maze (MWM), and GM1 administration did not improve performance on this task. Facilitation of passive avoidance acquisition was observed in animals receiving GM1 treatment after electrolytic or ibotenate lesions. Both types of injuries induced equivalent amounts of damage to the nucleus basalis but the electrolytic lesions produced greater damage to adjacent structures that could be responsible for the additional deficits observed on the MWM task. Show more

Keywords: nucleus basalis, electrolytic and ibotenic lesions, GM1 ganlioside treatment

Citation: Restorative Neurology and Neuroscience, vol. 15, no. 1, pp. 25-37, 1999

Authors: Goldstein, Larry B. | Bullman, Sarah

Article Type: Research Article

Abstract: Both age and sex can influence recovery after brain injury. To determine the impact of these variables on motor recovery, young (2 month old) and older (5-6 months old) male and female rats were first trained to traverse a narrow elevated beam. Rats then underwent suction-ablation of right sensorimotor cortex or sham operation. Motor recovery was measured by repeated testing on the beam over 3 weeks. Shamoperated rats performed perfectly regardless of age or sex throughout …testing. There was no difference in beam-walking scores among the groups of lesioned rats on the first trial 24 hrs. after injury (Kruskal-Wallis H = 0.18, p = 0.98). There was a significant effect of age (two-way ANOVA F1,32 = 29.58, p < 0.0001) but not sex (ANOVA F1,32 = 0.78, p = 0.38) on subsequent recovery. These data show that motor recovery after unilateral injury to the sensorimotor cortex varies with age, but not sex. Show more

Keywords: cortex, recovery, motor function, stroke, trauma, rat, aging, sex

Citation: Restorative Neurology and Neuroscience, vol. 15, no. 1, pp. 39-43, 1999

Authors: Kanthasamy, Anumantha G. | Tith, Tevy | Nguyen, Bang | Tran, Amy | Truong, Daniel D.

Article Type: Research Article

Abstract: A major consequence of severe cardiac arrest is impairment of neurological functions. Posthypoxic myoclonus and seizures are two of the major neurological problems following ischemic and hypoxic insults. This condition affects motor function to different degrees of severity ranging from mild to serious debilitation. The pathophysiological mechanism(s) associated with these neurological conditions remain elusive. Glutamate-mediated neuronal overexcitation is thought to play a major role in the neuronal damage and in the neurological …consequences of the posthypoxic state. Therefore, lamotrigine, a new anticonvulsant that indirectly modulates glutamatergic neurotransmission by interfering with voltage-dependent sodium channels, was tested for its effectiveness in controlling the neurological and histopathological changes in the animal model of cardiac arrest-induced myoclonus. Lamotrigine dose-dependently attenuated the audiogenic seizures and action myoclonus seen in this rat model. Histological analysis using Nissl staining and the novel Fluoro-Jade histochemistry in cardiac-arrested rats showed an extensive neuronal degeneration in the hippocampus and cerebellum. Lamotrigine treatment significantly attenuated the neuronal degeneration in these brain areas. The neuroprotective effect was more pronounced in hippocampal pyramidal and cerebellar Purkinje neurons. The therapeutic window of lamotrigine in this model was 8 hours. These results suggest that lamotrigine can be viewed as a potential antimyoclonic and neuroprotective agent for the treatment of posthypoxic myoclonus and seizures. The study also suggests that neuronal hyperexcitability may play a role in the etiology of posthypoxic myoclonus and seizure. Show more

Keywords: myoclonus, Na+ channel, global ischemia, motor function, seizure, neuroprotection

Citation: Restorative Neurology and Neuroscience, vol. 15, no. 1, pp. 45-56, 1999

Authors: Thanos, Panayotis K. | Okajima, Seiichiro | Tiangco, David A. | Terzis, Julia K.

Article Type: Research Article

Abstract: Among the pathological sequelae of facial paralysis is a paralytic eye. Apart from the psychological and aesthetic deficits, facial paralysis if left untreated can lead to dryness, ulceration and eventual blindness. Although numerous restorative microsurgical approaches have been introduced to address the sequelae of this problem, complete restoration of function to denervated facial muscles remains elusive. Utilizing the rat model of facial paralysis the present research has as an objective to examine a dual treatment approach. Specifically, this study combined the current microsurgical treatment of the cross-facial nerve graft with local administration of insulin-like growth factor I (IGF-I). The efficacy …of this combined approach (cross-facial nerve graft + IGF-I) was assessed in the following ways: (a) behavior measurement of the blink response and (b) histomorphometry light and electron microscopy of the entire nerve graft. These data will help provide insight into the restoration of facial muscle function after trauma and assist in the future development of more potent treatment strategies. 7he local adnünistration of IGF-I (50 µg/ml) to the cross-facial nerve graft was found to restore the blink response faster and to strengthen the degree of eye closure. Light microscopy examination revealed that IGF-I significantly enhanced axonal regeneration within a nerve graft (a 22% increase in the mean number of axons), and increased the mean nerve fiber diameter and myelin thickness. Electron microscopy assessment of the nerve grafts demonstrated that the IGF-I treated grafts possessed a greater density of microtubules, which were evenly distributed within the axoplasm. Show more

Keywords: blink reflex, axon, myelin, osmotic pump, neurotrophic, reinnervation

Citation: Restorative Neurology and Neuroscience, vol. 15, no. 1, pp. 57-71, 1999