Restorative Neurology and Neuroscience - Volume 25, issue 1

Authors: Barth, Alain | Guzman, Raphael | Andres, Robert H. | Mordasini, Pasquale | Barth, Laurence | Widmer, Hans R.

Article Type: Research Article

Abstract: Purpose: Current models of intracerebral hematoma are difficult to use for neurotransplantation studies because of high mortality and important variations of morphology, size and location of blood deposits. We propose a modification of the autologous blood infusion technique in rats to reduce these limitations. Methods: The modification consisted in a mechanical microlesion preceding blood infusion. A canula was stereotactically introduced into the striatum of adult rats. Subsequently, a parenchyma lesion was created …by a rotating microcatheter coaxially inserted through the canula, followed by slow infusion of 30 μl autologous blood during 5 minutes. Controls included canula insertion only and canula + microlesion. Hematoma volume/morphology were quantified and the animals behaviorally analysed using standardized tests. Results: Surgical mortality was 0/54 rats. One animal died during follow-up. Hematoma volume was constant and significantly higher (15.20 ± 0.60 mm^3 ) than control lesions (canula: 0.11 ± 0.01 mm^3 ; canula + trauma: 0.51 ± 0.01 mm^3 ). Hematoma edges were sharply delineated and the perihematomal region histologically preserved. Rats with hematoma showed initially a reduced spontaneous rotational behaviour. They also showed persisting deficits of forelimb placing ability. Conclusions: The advantages of this model include a systematic control of all steps of hematoma production, high reproducibility of volume, size, and location of blood deposits, preservation of perihematomal brain tissue, and quantifiable neurological deficits. Show more

Keywords: Hemorrhagic stroke, intracerebral, hematoma, rat

Citation: Restorative Neurology and Neuroscience, vol. 25, no. 1, pp. 1-7, 2007

Authors: Hesse, S. | Werner, C. | Schonhardt, E.M. | Bardeleben, A. | Jenrich, W. | Kirker, S.G.B.

Article Type: Research Article

Abstract: Background and Purpose: Preliminary reports suggest that central stimulation may enhance the effect of conventional physical therapies after stroke. This pilot study examines the safety and methodology of using transcranial direct stimulation (tDCS) with robot-assisted arm training (AT), to inform planning a larger randomised controlled trial. Subjects: Ten patients, after an ischaemic stroke 4–8 weeks before study onset, no history of epilepsy, participated. Eight had a cortical lesion and 2 had subcortical lesions: all had …severe arm paresis and, co-incidentally, 5 had severe aphasia. Methods: Over six weeks, they received thirty 20 min-sessions of AT. During the first 7 minutes, 1.5mA of tDCS was applied, with the anode over the lesioned hemisphere and the cathode above the contralateral orbit. Arm and language impairment were assessed with the Fugl-Meyer motor score (FM, full range 0–66) and the Aachener Aphasie Test. Results: No major side effects occurred. Arm function of three patients (two with a subcortical lesion) improved significantly, with FM scores increasing from 6 to 28, 10 to 49 and 11 to 48. In the remaining seven patients, all with cortical lesions, arm function changed little, FM scores did not increase more than 5 points. Unexpectedly, aphasia improved in 4 patients. Conclusions: These procedures are safe, and easy to use in a clinical setting. In future studies, patients should be stratified by degree of arm weakness and lesion site, also the unexpected aphasia improvement warrants following-up. Show more

Keywords: Stroke, rehabilitation, aphasia, plasticity, brain stimulation, recovery of function

Citation: Restorative Neurology and Neuroscience, vol. 25, no. 1, pp. 9-15, 2007

Authors: Lau, Wui-Man | Qiu, Guang | Helmeste, Daiga M. | Lee, Tatia M.C. | Tang, Siu-Wa | So, Kwok-Fai | Tang, Siu-Wa

Article Type: Research Article

Abstract: Purpose: Major depressive disorder is often associated with elevated glucocorticoid levels, which in turn suppress cell proliferation and neurogenesis in the hippocampus. Increasing evidence supports that antidepressants induce hippocampal neurogenesis and this induces speculation that decrease in hippocampal neurogenesis has causal relationship with depression. There is, however, a lack of information about neurogenic effects of antidepressants on the subventricular zone, which is another CNS region with continuous neurogenesis throughout adulthood. In the …present study, we investigated whether corticosterone and the SSRI paroxetine, have effects on SVZ cell proliferation. Methods: Rats were treated with the corresponding drugs for 14 days and the proliferating cells were labeled with bromodeoxyuridine (BrdU). BrdU labeled cells in the SVZ were quantified and analyzed. Results: In the corticosterone-treatment group, cell proliferation was decreased by 18% compared to vehicle-treatment group. Paroxetine-treatment group, in contrast, shows a 34% increase in cell proliferation. The decreased cell proliferation caused by corticosterone was prevented by paroxetine. Conclusions: Although corticosterone and antidepressants were found to affect cell proliferation in hippocampus, this is the first report to demonstrate that 1) corticosterone decreases cell proliferation in SVZ; 2) paroxetine promotes SVZ cell proliferation and 3) the suppressive effect on SVZ cell proliferation by corticosterone could be attenuated by paroxetine. These findings provide new insights into basic mechanisms of antidepressants, potential impact of steroid therapy on CNS neurogenesis, antidepressant mechanisms of action and potential involvement of the olfactory system in depression. Show more

Keywords: SSRI, paroxetine, corticosterone, neurogenesis, subventricular zone, major depressive disorder, depression, hypercortisolemia

Citation: Restorative Neurology and Neuroscience, vol. 25, no. 1, pp. 17-23, 2007

Authors: Ren, JingMei | Sietsma, Dana | Qiu, Shumei | Moessler, Herbert | Finklestein, Seth P.

Article Type: Research Article

Abstract: Background: Cerebrolysin, a preparation derived from porcine brain, contains a mixture of neurotrophic peptides. We tested the effects of Cerebrolysin in a model of stroke recovery in rats. Methods: Cerebrolysin (1.0, 2.5, or 5.0 ml/kg) was administered once daily intraperitoneally for 21 days, starting 24 hours after focal cerebral infarction (stroke) due to middle cerebral artery occlusion in mature rats. Results: Enhancement of sensorimotor recovery, as assessed by forelimb and hindlimb placing and body …swing tests, was seen with Cerebrolysin treatment, especially at the 2.5 ml/kg dose. At this dose, enhanced recovery was found when Cerebrolysin treatment was begun at 24 or 48 (but not 72 hours) after stroke onset. There were no effects on body weight or infarct volume when Cerebrolysin was administered in this manner. Conclusions: These results suggest that Cerebrolysin may be a useful treatment for enhancing neurological recovery after stroke. Show more

Keywords: Cerebrolysin, stroke recovery, rats

Citation: Restorative Neurology and Neuroscience, vol. 25, no. 1, pp. 25-31, 2007

Authors: Hildebrandt, Helmut | Lanz, Michael | Hahn, Horst K. | Hoffmann, Ebba | Schwarze, Björn | Schwendemann, Günther | Kraus, Jürgen A.

Article Type: Research Article

Abstract: Purpose: Cognitive disorders are common in MS patients without any generally recommended treatment. Recent brain imaging studies show considerable neuroplasticity for cognitive tasks in MS patients, but also brain atrophy already early in the disease progression. We explored the benefits of a home-based cognitive training program for memory and working memory functions in relapsing-remitting MS patients controlling for whole brain and central brain atrophy as covariates. Methods: Using a single-blinded controlled study …design, 42 patients were randomised into a treatment group and a control group. Home based computer training focusing on memory and working memory was started at least 4 weeks after the discontinuation of methylprednisolone treatment and lasted for 6 weeks. Two weeks later the patients were re-investigated for their clinical and cognitive performance. We assessed also quality of life (QoL), depression and fatigue using self-rating scales. Results: Training had no effect on the neurological status and on QoL or fatigue. However, the treatment group showed better verbal learning, long-delay verbal memory performance, and working memory performance. The impact of treatment on long-delay verbal memory performance was independent from the extent of brain atrophy, whereas for the other findings brain atrophy played a significant role. Conclusions: An intensive home-based cognitive training program is suitable to improve the cognitive performance of MS patients. The impact of brain atrophy on rehabilitation outcome may differ for cognitive functions. Show more

Keywords: Multiple sclerosis, cognitive training, memory, working memory, brain atrophy

Citation: Restorative Neurology and Neuroscience, vol. 25, no. 1, pp. 33-43, 2007

Authors: Pannucci, Christopher | Myckatyn, Terence M. | Mackinnon, Susan E. | Hayashi, Ayato

Article Type: Research Article

Abstract: End-to-side (ETS) nerve repair, in which the distal stump of a transected nerve is coapted to the side of an uninjured donor nerve, offers a technique for repair of peripheral nerve injuries where the proximal nerve stump is unavailable or a significant nerve gap exists. Details of animal models are explored including motor and sensory regeneration to further clarify the mechanism of collateral sprouting while eliminating false positive results from contaminating axons. Some experimental studies support …the conclusion that sensory or motor reinnervation may be derived from collateral sprouting while others suggest that reinnervation requires an injury to the donor nerve. Clinical experience with ETS neurorrhaphy includes management of upper extremity nerve injury, facial reanimation, reconstruction following tumor ablation, and the prevention of neuroma formation. Our interpretation of the ETS literature suggests that sensory axons may sprout without deliberately attempting to injure them, while motor axons regenerate only in response to a deliberate injury. Experimental and clinical experience with ETS neurorrhaphy has rendered mixed results. Our interpretation of the literature suggests that the success of this technique is dependent upon axonal injury of motor and possibly sensory nerves. While continued clinical and laboratory experimentation with ETS nerve repair is warranted, it should not yet replace more established techniques of nerve repair. Show more

Keywords: End-to-side neurorrhaphy, nerve repair, reinnervation, sensory regeneration, nerve sprouting

Citation: Restorative Neurology and Neuroscience, vol. 25, no. 1, pp. 45-63, 2007

Authors: Urrea, Carlos | Castellanos, Daniel A. | Sagen, Jacqueline | Tsoulfas, Pantelis | Bramlett, Helen M. | Dietrich, W. Dalton

Article Type: Research Article

Abstract: Purpose: A proliferation of stem/progenitor cells is observed after brain injury. We examined the regional and temporal profile of mitotically active cells to determine whether traumatic brain injury (TBI) would increase neurogenesis in selective brain regions. Methods: Male Sprague-Dawley rats received injections (IP) of 5-bromo-deoxyuridine (BrdU), a compound used to detect mitotic cells, before and after fluid-percussion brain injury. At 3 hr, 1, 2, 3, 7, and 14 days after moderate fluid percussion, brains …were processed for immunocytochemical and confocal analysis. Sections were double-labeled for markers selective for neurons (NeuN), astrocytes (GFAP), olidgodendrocytes (CNPase and MBP) and macrophage/microglia (ED1). Results: At 3 hr post-trauma, the majority of BrdU labeled cells were associated with the subventricular zone of the traumatized hemisphere. At later time points, a significant increase in BrdU positive cells was observed throughout the traumatized cerebral cortex, hippocampus, white matter structures, and some contralateral regions. BrdU labeled cells were observed as late as 14 days post-injury. Double-label studies with confocal microscopy demonstrated that cell phenotypes including astrocytes, macrophage/microglia, oligodendrocytes, and neurons were BrdU positive with the majority of cells appearing glial in nature. Evidence for neurogenesis was seen in the granular cell layer of the hippocampus. Conclusion: These findings indicate that TBI stimulates widespread cellular proliferation for days after injury and results in focal neurogenesis in the dentate gyrus of the hippocampus. These cellular responses to injury may participate in brain repair and functional recovery. Show more

Keywords: Neurogenesis, dentate granular neurons, trauma, subventricular zone, plasticity

Citation: Restorative Neurology and Neuroscience, vol. 25, no. 1, pp. 65-76, 2007