Restorative Neurology and Neuroscience - Volume 34, issue 2

Authors: Palmateer, Julie | Pan, Jie | Pandya, Arushi | Martin, Lianna | Kumar, Sungita | Ofomata, Adaora | Jones, Theresa A. | Gore, Andrea C. | Schallert, Timothy | Hurn, Patricia D.

Article Type: Research Article

Abstract: Purpose: Approximately one-fourth of stroke survivors are aphasic. Speech therapy is the main treatment approach but leaves most patients with chronic disability. Attempts to improve this situation are hampered by a lack of mechanistic understanding of the disability and treatments, reflecting the neglect of this impairment modality in pre-clinical research. Accordingly, we devised a novel murine model of speech-related impairment after stroke to investigate the role of language- and plasticity-associated molecules. Rodents communicate socially with ultrasonic vocalizations (USVs), conveying semantic and semiotic information with complex frequency modulated “songs” and alarm calls. Methods: Transient focal cerebral ischemia was …induced in male C57BL6 mice via either 30 or 45 minutes of reversible right MCAO using the intraluminal filament technique. Nine days post-operatively brains are stained with TTC and analyzed for infarct volume. For behavioral measures health scores are taken (days 1–4), cylinder tests and USV recordings performed at days 3 and 7 post operatively. Real time PCR was performed at 24 and 48 hour and 7 day time points to quantify mRNA expression of communication-related genes (Foxp2, Foxp1, Srpx2, Cntnap2 and Gapdh ). Immunohistochemistry was performed to localize FOXP2 protein. Results: After middle cerebral artery occlusion of either 30 or 45 minutes duration, mice demonstrate profoundly impaired socially evoked USVs. In addition, there is suppression of the language-associated transcription factor, Forkhead box protein 2 (Foxp2 ), and its downstream binding partner, contactin-associated protein 2 (Cntnap2 ). Conclusion: These findings set a foundation for further studies of mechanisms and novel treatment strategies for post-stroke vocalization impairments. Show more

Keywords: Cerebral ischemia, contactin-associated protein 2, Forkhead box protein 2, stroke, ultrasonic vocalization

DOI: 10.3233/RNN-150583

Citation: Restorative Neurology and Neuroscience, vol. 34, no. 2, pp. 287-295, 2016

Authors: van Vugt, F.T. | Kafczyk, T. | Kuhn, W. | Rollnik, J.D. | Tillmann, B. | Altenmüller, E.

Article Type: Research Article

Abstract: Purpose: Learning to play musical instruments such as piano was previously shown to benefit post-stroke motor rehabilitation. Previous work hypothesised that the mechanism of this rehabilitation is that patients use auditory feedback to correct their movements and therefore show motor learning. We tested this hypothesis by manipulating the auditory feedback timing in a way that should disrupt such error-based learning. Methods: We contrasted a patient group undergoing music-supported therapy on a piano that emits sounds immediately (as in previous studies) with a group whose sounds are presented after a jittered delay. The delay was not noticeable to …patients. Thirty-four patients in early stroke rehabilitation with moderate motor impairment and no previous musical background learned to play the piano using simple finger exercises and familiar children’s songs. Results: Rehabilitation outcome was not impaired in the jitter group relative to the normal group. Conversely, some clinical tests suggests the jitter group outperformed the normal group. Conclusions: Auditory feedback-based motor learning is not the beneficial mechanism of music-supported therapy. Immediate auditory feedback therapy may be suboptimal. Jittered delay may increase efficacy of the proposed therapy and allow patients to fully benefit from motivational factors of music training. Our study shows a novel way to test hypotheses concerning music training in a single-blinded way, which is an important improvement over existing unblinded tests of music interventions. Show more

Keywords: Stroke rehabilitation, sensorimotor integration, music intervention, timing, auditory feedback, motor learning

DOI: 10.3233/RNN-150588

Citation: Restorative Neurology and Neuroscience, vol. 34, no. 2, pp. 297-311, 2016

Authors: Bates, Kristyn A. | Drummond, Eleanor S. | Cozens, Greg S. | Harvey, Alan R.

Article Type: Research Article

Abstract: Purpose: There is considerable variability in the extent and nature of the glial response to injury and neurodegeneration. Transplantation of fetal cortical tissue onto the brain of neonatal host rats or mice results in region-specific changes dependent on where the fetal tissue is placed. These changes include chronic astrocytic and microglial gliosis, oxidative stress, and altered metabolism of a number of proteins associated with the pathogenesis of Alzheimer’s disease. Such changes are only observed in heterotopic (cortex-to-midbrain) grafts and are not observed in homotopic cortex-to-cortex grafts. We investigated two possible triggers for the region-specific gliosis observed in our transplant …model hypothesizing that either i) poor vascularization and lack of blood brain barrier integrity or ii) an inflammatory response initiated by the transplantation process, contributed to establishing chronic pathological changes. Methods: We analyzed the time course of neovascularization, blood brain barrier permeability and inflammation using a combination of immunohistochemistry, enzyme-linked immunosorbant assay and Evan’s blue dye extravasation techniques. Results: Blood brain barrier permeability and altered neovascularization occurred prior to the onset of gliosis in heterotopic grafts. Conclusion: These data suggest that ischemic conditions and blood brain barrier damage can be a primary mechanism that initiates chronic gliosis and associated inflammatory changes in central nervous system tissue. Show more

Keywords: Astrocytes, transplantation, inflammation, blood brain barrier, gliosis, neovascularization

DOI: 10.3233/RNN-150591

Citation: Restorative Neurology and Neuroscience, vol. 34, no. 2, pp. 313-323, 2016

Authors: Chen, Tianli | Yu, Yong | Hu, Chengliang | Schachner, Melitta

Article Type: Research Article

Abstract: Purpose: The aim of the study was to investigate the functional role of L1.2, the zebrafish paralog of L1.1 and ortholog of mammalian L1CAM in adult zebrafish spinal cord regeneration after injury. L1CAM and L1.1 have shown beneficial features in ameliorating nervous system dysfunctions in different experimental paradigms. It thus deemed important to characterize the L1.2 member of the L1CAM family, the functions of which are unknown. Methods: Spinal cord transection of adult zebrafish, application of anti-sense morpholino to reduce L1.2 expression, qPCR, immunohistology, immunoblotting, in situ hybridization, retrograde tracing, anterograde tracing. Results: Similar …to L1.1, L1.2 expression in adult zebrafish is upregulated after spinal cord transection. By co-localization of in situ hybridization and immunohistology, L1.2 is expressed in neurons and, in contrast to L1.1, it is also expressed in GFAP-immunoreactive glia. Reducing L1.2 protein levels leads to impaired locomotor recovery and reduction of regrowth of severed descending axons from a brain stem nucleus which is composed of neurons innately capable of axonal regrowth. Conclusions: Our findings support the speculation that paralogs of duplicated genes can exert similar functions and may thus represent an advantage over other species that do not carry duplicated genes. Show more

Keywords: Adhesion molecule L1, morpholino, Danio rerio, regeneration, spinal cord injury

DOI: 10.3233/RNN-150602

Citation: Restorative Neurology and Neuroscience, vol. 34, no. 2, pp. 325-335, 2016

Authors: Washabaugh, Edward P. | Krishnan, Chandramouli

Article Type: Research Article

Abstract: Purpose: Accurate coil placement over a target area is critical during transcranial magnetic stimulation (TMS), as small deviations can alter testing outcomes. Accordingly, frameless stereotaxic systems (FSS) are recommended for reliable coil placement during TMS applications. However, FSS is not practical due to the cost associated with procuring such systems. Therefore, the purpose of this study was to develop a low-cost TMS coil tracking approach using simple webcams and an image processing algorithm in LabVIEW Vision Assistant. Methods: A system was created using two webcams, retroreflective markers, and computer stereovision, for tracking the TMS coil over a …target area. Accuracy of the system was validated in both the global and local reference frames, while repeatability was measured within- and between-days for placement of the TMS coil over the target area relative to the head. The feasibility of our system was also verified by collecting motor evoked potentials (MEPs) of first dorsal interosseous muscle from human subjects. Results: The results of this study indicated that the system was highly accurate and repeatable, and could track the coil position with <5 mm error and orientation <1.1° error from the target. We also observed larger and more consistent MEPs when stimulating the brain using feedback from the coil tracking system than when the examiner attempted to stimulate without any feedback. Conclusion: The findings suggest that webcam-based coil tracking is a feasible low-cost solution to track coil positions during TMS procedures. Show more

Keywords: Neuronavigation, motion tracking, motor mapping, real time, stereotaxy

DOI: 10.3233/RNN-150609

Citation: Restorative Neurology and Neuroscience, vol. 34, no. 2, pp. 337-346, 2016