Restorative Neurology and Neuroscience - Volume 24, issue 1

Authors: Federico, Francesca | Leggio, Maria G. | Mandolesi, Laura | Petrosini, Laura

Article Type: Research Article

Abstract: Purpose: To test whether activation of NMDA receptors is required for the maintenance of the posture and motor behavior recovered from cerebellar lesions, an NMDA antagonist (CGS 19755) was systemically administered to totally or partially cerebellectomized rats. Methods: Three groups of animals were tested: rats that had undergone a total cerebellectomy four months before drug administration; rats that had undergone a right hemicerebellectomy four months before drug administration; intact control animals. Results: …Under drug action in the control animals the postural pattern was slightly influenced, showing a light worsening, and motor skills requiring coordinated motor performance and subtle balance control were markedly worsened. Conversely, in the lesioned groups the cerebellar symptomatology dramatically worsened, and both groups of animals looked like they had just been operated, exhibiting the whole repertoire of postural and motor behaviors of cerebellar origin. In particular, limb hyperflexion, wide-based locomotion and the tendency to side falls were prevalent in the cerebellectomized animals, while tremor and body tilt were prevalent in the hemicerebellectomized group. Conclusion: The reappearance of severe postural and motor symptomatology has to be interpreted as a "decompensation" evoked by the NMDA-receptor antagonist, suggesting the involvement of NMDA receptors in the maintenance of compensation of disturbances of cerebellar origin. Show more

Keywords: Cerebellar compensation, neural plasticity, motor behavior, posture, glutamate receptors, rat

Citation: Restorative Neurology and Neuroscience, vol. 24, no. 1, pp. 1-7, 2006

Authors: Taupin, Philippe

Article Type: Research Article

Abstract: After cerebral strokes and traumatic brain injuries (TBIs), there is a striking amount of neurological recovery in the following months and years, despite often-permanent structural damage. Though the mechanisms underlying such recovery are not fully understood, properties of plasticity of the central nervous system (CNS), such as the reorganization of the pre-existing network and axonal sprouting have been implicated in the recovery. With the recent evidences that neurogenesis occurs in the adult brain, and neural stem …cells (NSCs) reside in the adult CNS, the involvement of newly generated neuronal cells in the recovery following injury to the CNS remains to be established. Neurogenesis is increased bilaterally in the dentate gyrus (DG) and the subventicular zone (SVZ) after cerebral strokes and TBIs, and new neuronal cells are generated at the sites of injury, where they replace some of the degenerated nerve cells. Newly generated neuronal cells at the sites of injury may represent an attempt by the CNS to regenerate itself after injury, whereas the increased neurogenesis in the DG and SVZ would also contribute to the CNS plasticity. Thus, injury-induced neurogenesis may contribute to the recovery and plasticity of the CNS. Show more

Keywords: Stem cell, progenitor cell, stroke, brain injury, sprouting, regeneration, cellular therapy

Citation: Restorative Neurology and Neuroscience, vol. 24, no. 1, pp. 9-15, 2006

Authors: Sonninen, Riitta | Virtanen, Tiina | Sivenius, Juhani | Jolkkonen, Jukka

Article Type: Research Article

Abstract: Purpose: Enriched environment housing enhances brain plasticity and improves recovery of impaired sensorimotor and cognitive functions of rats subjected to transient middle cerebral artery occlusion (MCAO). The present study applied microarray technique to investigate the molecular basis through which enriched environment might improve spatial learning in MCAO rats. Methods: MCAO rats were housed in enriched environment or in standard single cages, and sham-operated rats were housed in standard single cages. Spatial learning was assessed …using the Morris water-maze on postoperative days 22 to 24. Total RNA from the ipsilateral hippocampus was extracted for microarray analysis after the follow-up period. Results: Water-maze performance on postoperative days 22 to 24 showed that rats subjected to transient MCAO were impaired in the hippocampus-dependent Morris water-maze test. Enriched environment housing reversed the spatial learning impairment on postoperative day 23. Gene expression in the hippocampus was not affected by MCAO or following enriched environment housing. Conclusion: Spatial learning impairment following transient MCAO in rats and cognitive improvement following housing in enriched environment may not be related to altered hippocampal gene expression. Show more

Keywords: Enriched environment, focal cerebral ischemia, microarray, spatial learning

Citation: Restorative Neurology and Neuroscience, vol. 24, no. 1, pp. 17-23, 2006

Authors: Jang, Sung Ho | Byun, Woo Mok | Han, Bong Soo | Park, Hae-Jeong | Bai, Daiseg | Ahn, Young Hwan | Kwon, Yong-Hyun | Lee, Mi Young

Article Type: Research Article

Abstract: Purpose: We hypothesized that diffusion tensor imaging (DTI) could be useful for exploring corticospinal tract (CST) regeneration if longitudinal changes of diffusion anisotropy can be detected. In this study, we explored the recovery of a CST partially damaged by intracerebral hematoma in a patient by DTI. Methods: A 61-year-old female patient and six age-matched control subjects were evaluated. The patient presented with complete paralysis of the left extremities, which occurred at the onset of …a spontaneous intracerebral hemorrhage (ICH) in the right corona radiata and internal capsule. Over the five-month period following onset, motor function of the affected extremities slowly recovered to the normal range. Two longitudinal DTIs were acquired from the patient (at 3 weeks and 5 months from onset) and one DTI from the control subjects. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured using a region of interest (ROI) method. Results: On the 3-week DTI, FA values of ROIs in the ICH regions in the affected hemisphere were significantly lower, and ADC values of ROIs in the same areas were significantly higher than those of the control subjects (p<0.002). However, both mean FA and ADC values of the affected hemisphere in the 5-month DTI showed no significant differences versus those of the control. Show more

Citation: Restorative Neurology and Neuroscience, vol. 24, no. 1, pp. 25-29, 2006

Authors: Duret, Florence | Brelén, Måten E. | Lambert, Valerie | Gérard, Benoît | Delbeke, Jean | Veraart, Claude

Article Type: Research Article

Abstract: Purpose: This study involved a volunteer completely blind from retinis pigmentosa who had previously been implanted with an optic nerve visual prosthesis. The aim of this two-year study was to train the volunteer to localize a given object in nine different positions, to discriminate the object within a choice of six, and then to grasp it. Methods: In a closed-loop protocol including a head worn video camera, the nerve was stimulated whenever a part of the processed image …of the object being scrutinized matched the center of an elicitable phosphene. The accessible visual field included 109 phosphenes in a 14° × 41° area. Results: Results showed that training was required to succeed in the localization and discrimination tasks, but practically no training was required for grasping the object. The volunteer was able to successfully complete all tasks after training. The volunteer systematically performed several left-right and bottom-up scanning movements during the discrimination task. Discrimination strategies included stimulation phases and no-stimulation phases of roughly similar duration. Conclusion: This study provides a step towards the practical use of the optic nerve visual prosthesis in current daily life. Show more

Keywords: Visual prosthesis, blindness, optic nerve, electrical stimulation, object discrimination

Citation: Restorative Neurology and Neuroscience, vol. 24, no. 1, pp. 31-40, 2006

Authors: Dow, Douglas E. | Carlson, Bruce M. | Hassett, Cheryl A. | Dennis, Robert G. | Faulkner, John A.

Article Type: Research Article

Abstract: Purpose: Denervated skeletal muscles lack contractile activity and subsequently lose mass and force generation. Prolonged periods of denervation prior to nerve-implant grafting limit the recovery of mass and force. We hypothesized that electrical stimulation during a period of denervation that maintains mass and force above the levels of denervated muscles enhances the recovery of mass and force following nerve-implant grafting. Methods: The extensor digitorum longus (EDL) muscles of anesthetized rats were denervated, and a …stimulator was implanted. Following 4 or 7 months of denervation, with or without electrical stimulation, the EDL muscles were removed, evaluated in vitro for mass and contractile properties, and then nerve-implant grafted into syngeneic rats. Unoperated, contralateral muscles were also evaluated and grafted. Results: The hypothesis was not supported by the experimental data. Compared with values for 4- or 7-month denervated muscles, the stimulated-denervated muscles maintained higher mass and force, less prolonged time-to-peak tensions and half-relaxation times, and higher excitability. Nevertheless, the recovery of mass and force following grafting was not improved. Conclusion: The factors within long-term denervated muscles that hinder recovery following grafting appear to be related primarily to factors associated with the duration of denervation and not to the level of atrophy and weakness prior to grafting. Show more

Keywords: Extensor digitorum longus, EDL, contractility, excitability, implantable stimulator, transplantation, reinnervation, degeneration, regeneration

Citation: Restorative Neurology and Neuroscience, vol. 24, no. 1, pp. 41-54, 2006

Authors: Kunz, Tina | Marklund, Niklas | Hillered, Lars | Oliw, Ernst H.

Article Type: Research Article

Abstract: Purpose: Lateral fluid percussion brain injury (FPI) increases cyclooxygenase-2 (COX-2) expression in the cortex and hippocampus. The objective was to investigate whether the selective COX-2 inhibitor rofecoxib (10 mg/kg twice daily) reduces neuronal cell death after FPI in rats, since rofecoxib has been shown to be neuroprotective in other models of CNS injury. Methods: Rofecoxib (n=23) or vehicle (n=20) were administered after FPI and for up to 3 days. Cell death was evaluated by …Fluoro-Jade B staining and by the TdT-mediated dUTP nick end labelling (TUNEL) assay. Results: COX-2 immunoreactivity increased in the ipsilateral cortex and hippocampus (CA1) and bilaterally in the dentate gyri. Fluoro-Jade B- and TUNEL-positive cells were detected 12–72 h after FPI in the ipsilateral cortex and bilaterally in the dentate gyri. Fluoro-Jade B staining did not indicate a significant neuroprotective effect of rofecoxib (12–72 h) and neither did TUNEL staining. Quantificaton of the TUNEL staining in the ipsilateral cortex was ∼50% lower in the rofecoxib group at 12 and 24 h, but this did not reach statistical significance (p=0.06), and appeared unchanged at 72 h. Conclusions: Rofecoxib lacked significant protective effect on early neuronal cell death in the FPI model of traumatic brain injury. Show more

Keywords: COX-2 inhibitor, fluid percussion brain injury, Fluoro-Jade B, neuroinflammation, prostaglandins, TUNEL staining

Citation: Restorative Neurology and Neuroscience, vol. 24, no. 1, pp. 55-63, 2006