Restorative Neurology and Neuroscience - Volume 17, issue 4

Authors: Grigoryan, G.A. | Gray, J.A. | Rashid, T. | Chadwick, A. | Hodges, H.

Article Type: Research Article

Abstract: Purpose: Loss of cholinergic projections from the basal forebrain (BF) to the cortex and from the medial septal area (MSA) to tbe hippocampus is a reliable correlate of cognitive deficits in aging and Alzheimer's disease (AD). We assessed the capacity of grafts of the conditionally immortal MHP36 clonal stem cell line to improve spatial learning in rats showing profound deficits after lesions to these projections. Methods: Rats were lesioned by infusions of S-AMPA unilaterally into BF …or bilaterally into both BF and MSA. MHP36 cells were implanted ipsilaterally in cortex or basal forebrain two weeks after unilateral BF lesions, and in cortex and hippocampus bilaterally six months after bilateral BF-MSA lesions. Intact and lesion-only controls received vehicle. Six weeks later rats were assessed in spatial learning and memory tasks in the water maze, and then perfused for identification of grafted cells by β-galactosidase immunohistocheniistry. Results: Lesioned rats with MHP36 grafts, whether implanted two weeks or six months after lesioning, learned to find a submerged platform in the water maze as rapidly as intact controls, and showed a strong preference for the platform quadrant on probe trials, whereas lesioned controls were impaired in all measures. Grafted cells of both neuronal and glial morphologies, migrated away from cortical implantation sites in BF Lesioned rats to the striatum, thalamus and basal forebrain lesion area. Cells implanted in basal forebrain showed a similar distribution. In rats with bilateral BF-MSA lesions, grafts implanted in the hippocampus migrated widely through all layers but cortical grafts largely escaped up the needle tract into the meninges. Conclusions: Although MHP36 grafts were functionally effective in both lesion models, the site and age of lesions and site of implantation influenced the pattern of engraftment. This flexibility encourages the development of conditionally immortal human stem cell lines with similar capacities for functional repair of variable neuronal degeneration in AD or aging. Show more

Keywords: cholinergic lesions, conditionally immortal stem cells, water maze, β-galactosidase

Citation: Restorative Neurology and Neuroscience, vol. 17, no. 4, pp. 1-1, 2000

Authors: Steinsapir, Kenneth D. | Goldberg, Robert A. | Sinha, Shini | Hovda, David A.

Article Type: Research Article

Abstract: Purpose: This study investigates the clinical dogma that very high doses of methylprodnisolone helpful in spinal cord injury are also helpful in optic nerve trauma. Methods: The right optic nerve of 29 male rats received a 5 second traumatic crush followed 30 minutes later by one of five intravenous treatments (methylprednisolone 30 mg/kg, 60 mg/kg, 90 mg/kg, 120 mg/kg, or saline). Treatment was continued for three additional administrations at 6 hour intervals. Untreated sham controls (n …= 7) were also prepared. Six weeks after injury, animals were sacrificed, perfused and optic nerves systematically counted. Results: Axon counts (means ± s.e.m.) were as follows: Saline = 16,670 ± 8,900 (n = 5); Methylprednisolone: 30 mg/kg = 8,098 ± 4,741 (n = 5); 60 mg/kg = 6,925 ± 6,517 (n = 4); 90 mg/kg = 2,663 ± 2,653 (n = 4); 120 mg/kg = 6,149 ± 3,487 (n = 6). Consequently, the data revealed that saline treated animals retained more axons than those that were administered methylprednisolone (p < 0.02). Conclusions: We conclude that methylprednisolone exacerbates axonal loss following crush injury in the rat optic nerve. Based on the results of this study, clinical studies of traumatic optic neuropathy in the future should also examine the possibility that corticosteroid treatment may have an adverse effect on visual outcome following optic nerve trauma. Show more

Keywords: Corticosteroids, methylprednisolone, optic nerve injury, traumatic optic neuropathy, TON

Citation: Restorative Neurology and Neuroscience, vol. 17, no. 4, pp. 157-163, 2000

Authors: Arai, Takeru | Kanje, Martin | Lundborg, Göran | Sondell, Mariann | Liu, Xiao-Lin | Dahlin, Lars B.

Article Type: Research Article

Abstract: Purpose: To compare nerve regeneration in autologous detergent extracted and freeze-thawed muscle grafts and to electrophoretically characterize the grafts. Methods: Autologous acellular muscie grafts were created either by freeze/thawing or by detergent extraction and then used to bridge a 10 mm gap in rat sciatic nerve. The autologous grafts were compared with respect to protein content, using electrophoresis preimplantation, and axonal outgrowth, Schwann cell and macrophage content, using immunocytochemistry (neurofilaments, S-100 protein, …ED 1 macrophages) at 520 days postimplantation. Results: The extracted muscle grafts were elastic, but the amount of several proteins was reduced and laminin was still present at a position of basal laminae of the muscle fibers. The freeze/thawed grafts were brittle and lacked elasticity, but resulted in minor changes in major proteins. The axons regenerated through both types of grafts (initial delay 6 days and rate 0.7-0.8 mm/day), which shrunk in length by 25%. There were no apparent differences with respect to Schwann cells and macrophages. Conclusions: The results suggest that detergent extracted muscle tissue, in which some basal lamina proteins remain but cells are removed, could present a new favourable option for nerve grafting. Show more

Keywords: Nerve regeneration, nerve grafts, extraction, axons, Schwann cells, macrophages, muscle

Citation: Restorative Neurology and Neuroscience, vol. 17, no. 4, pp. 165-174, 2000

Authors: Laubis-Herrmann, U. | Dichgans, J. | Bilow, H. | Topka, H.

Article Type: Research Article

Abstract: Purpose: Given that SCI leads to substantial changes in biomechanical properties of the body and to widespread postlesional reorganization of the motor system as determined by functional imaging studies, we sought to identify neurophysiological correlations and time course of reorganization affecting muscles more distant to a SCI. Methods: Two arm muscles distant to a SCI (T2-L3), M.biceps brachii (BIC), M.abductor pollicis brevis (APB), were studied in 13 SCI-patients and 15 controls. Motor …thresholds at rest (MT), facilitatory effects on MEP-amplitudes (FE) with voluntary activation, MEP-amplitudes with maximal stimulation (MA) and recruitment curves (RC) were measured and correlated with level, age and severity of the lesion. Follow-up studies (t2) were performed in five patients with clinical recovery. Results: Patients exhibited smaller MA from activated BIC, a tendency towards smaller FE and smaller RC-slopes at t1. With clinical recovery, activated BIC-FE, MA and RC-slopes tended to normalize. Conclusions: Our data support the hypothesis that postlesional reorganization of the motor system also involves remote muscles. Considering pattern and time course of reorganization, we speculate that they appear as sequelae of the trauma, possibly representing an adaptation of the motor system to an altered biomechanical status after SCI. Show more

Keywords: Spinal cord injury, transcranial magnetic stimulation, postlesional reorganization, motor system, biomechanical changes

Citation: Restorative Neurology and Neuroscience, vol. 17, no. 4, pp. 175-181, 2000

Authors: Li, Xiuming | Oudega, Martin | Dancausse, Hector A. | Levi, Allan D.O.

Article Type: Research Article

Abstract: Purpose: Caspase-3 is known as a crucial effector for apoptotic cell death. Apoptosis has recently been recognized as an important cell death mechanism after spinal cord injury (SCI). This study attempts to define the effect of methylprednisolone (MP) on the activation of caspase-3 in the lesioned area following SCI. Methods: Forty-eight rats with a complete transection of the thoracic spinal cord received a placebo or MP (30 mg/kg, iv.) at 5 min, 2 and 4 h …post-injury and were then sacrificed at 12, 24 h, 3 or 7 days thereafter. Results: Caspase-3 positive cells in the lesioned area were immunocytochemically observed in both cord stumps and decreased in number with increasing distance from the lesion site. More caspase-3 positive cells were present in the MP-treated group than the control group at all time points, but the differences were not statistically significant. Conclusion: These results suggest that the MP-induced decrease of tissue loss following SCI may not involve a reduction of apoptotic cell death. Show more

Keywords: apoptosis, caspase-3, immunocytochemistry, methylprednisolone, secondary damage, spinal cord injury

Citation: Restorative Neurology and Neuroscience, vol. 17, no. 4, pp. 203-209, 2000

Authors: Jolkkonen, Jukka | Puurunen, Kirsi | Rantakömi, Sanna | Sirviö, Jouni | Haapalinna, Antti | Sivenius, Juhani

Article Type: Research Article

Abstract: Purpose: The present study investigated the effects of fluoxetine, a serotonin reuptake blocker, on behavioral deficits of rats subjected to transient focal cerebral ischemia. Methods: The right middle cerebral artery of rats was occluded for 120 min using the intraluminal filament method. Fluoxetine treatment (5 mg/kg, i.p.) was started 2 days after ischemia induction and treatment was continued for 10 days thereafter. Sensorimotor recovery was assessed using the limb-placing test and cognitive impairment was …assessed using a water-maze test at the end of the experiment. Results: Fluoxetine treatment did not improve performance of ischemic rats in the limb-placing test. Nor was the ischemia-induced deficit in the water-maze test affected by fluoxetine. The infarct volumes in the cortex or striatum, determined after the experiment, were not different between ischemic groups. Conclusion: These results suggest that subchronic fluoxetine treatment following experimental focal cerebral ischemia is not detrimental to behavioral outcome, but it also does not enhance spontaneous sensorimotor recovery or attenuate spatial learning deficits. Show more

Keywords: behavioral deficits, focal cerebral ischemia, recovery of function, serotonin

Citation: Restorative Neurology and Neuroscience, vol. 17, no. 4, pp. 211-216, 2000

Authors: Cruz-Aguado, Reyniel | Turner, Liliana Francis | Díaz, Carmen M. | Piñero, Janet

Article Type: Short Communication

Abstract: Purpose: To test the influence of nerve growth factor (NGF) on striatal glutathione (GSH) content and the activities of GSH-related enzymes from quinolinic acid-lesioned rats. Methods: Rats were intrastriatally injected with QA and NGF. Enzymatic and GSH assays were performed one week later. Results: NGF prevented the QA-induced decline in glutathione reductase activity and GSH content. Conclusions: NGF is able to prevent some of the disturbances induced by the excitotoxic insult in the striatal GSH metabolism.

Keywords: nerve growth factor, glutathione, quinolinic acid, Huntington's disease, oxidative stress, striatum

Citation: Restorative Neurology and Neuroscience, vol. 17, no. 4, pp. 217-221, 2000