Restorative Neurology and Neuroscience - Volume 22, issue 6

Authors: Sabel, Bernhard A. | Kenkel, Sigrid | Kasten, Erich

Article Type: Research Article

Abstract: Purpose: We wished to evaluate the efficacy of vision restoration therapy (VRT) in patients with post-chiasmatic brain damage using different functional perimetric tests. These were compared with measures of subjective vision and reaction time. Methods: An open trial was conducted with hemianopia/scotoma (n = 16) patients. Before and after 6 months of VRT results of high resolution (HRP) and Tuebingen automated perimetry (TAP) were evaluated and compared to performance in a Scanning Laser Ophthalmoscope …(SLO) as previously reported. Whereas TAP and HRP used above-threshold or near-threshold individual target stimuli on grey background, the SLO used a psychophysical task of detection of three black targets (reverse stimulus) on bright red, patterned background. Subjective testimonials of activities of daily living (ADL) were probed with questionnaires and interviews. Results: Before VRT, the visual field border as assessed by SLO was located significantly closer to the vertical midline than the HRP and TAP border (border mismatch). After VRT the SLO border was still unchanged whereas HRP measurements revealed significant border shifts due to improved stimulus detection (p < 0.0001) and improved reaction time (p < 0.005) . Fewer misses were also observed in both eyes with TAP (p < 0.01) which was primarily due to a significant shift of the absolute borders. Thus, VRT potentiated the mismatch between the SLO borders and the HRP/TAP borders. Fixation performance and the blind spot position remained unchanged after VRT. ADL ratings in the questionnaire improved significantly after VRT which was confirmed by independent patient testimonials. Conclusions: We replicated earlier findings that VRT improves stimulus detection in HRP and TAP perimetry which were accompanied by subjective, visual improvements. These changes are not caused by fixation or eye movement artifacts. Because the SLO border was located significantly closer to the vertical midline before VRT ("border mismatch") and, in contrast to HRP and TAP, did not change after VRT, we interpret this border mismatch to indicate that the SLO task was too difficult to perform and thus insensitive to VRT effects. Significant reaction time improvements indicate that plasticity of temporal processing might play an important role in vision restoration after brain damage. A further description of the precise psychophysical nature of the restored areas of residual vision is now warranted. Show more

Keywords: hemianopia, scotoma, visual field defect, computer training, high resolution perimetry, rehabilitation, vision, training, therapy, plasticity

Citation: Restorative Neurology and Neuroscience, vol. 22, no. 6, pp. 399-420, 2004

Authors: Zeng, Xianmin | Chen, Jia | Liu, Ying | Luo, Yongquan | Schulz, Thomas C. | Robins, Allan J. | Rao, Mahendra S. | Freed, William J.

Article Type: Research Article

Abstract: Purpose: To explore a karyotypically abnormal variant human embryonic stem cell (hESC) line, BG01V, as a potential model for studies of dopaminergic neuronal differentiation. Methods: The properties of BG01V cells were compared to those of normal BG01 cells using immunocytochemistry, RT-PCR, focused microarrays and in vitro differentiation, including dopaminergic differentiation, by culturing with the stromal cell line PA6. Results: Despite the karyotypic abnormality (49, +12, +17 and XXY), undifferentiated BG01V cells …expressed pluripotent ESC markers similar to BG01 cells, and retained the ability to differentiate into cell types characteristic of all three germ layers. When co-cultured with the stromal cell line PA6, BG01V cells differentiated into dopaminergic cells which exhibited properties similar to those of mature dopaminergic neurons. Conclusions: BG01V cells were easier to maintain in culture than karyotypically normal BG01 cells and can be used as an alternative pluripotent hESC type for in vitro developmental studies. Show more

Keywords: hESCs, karyotype, dopaminergic differentiation, PA6 stromal cells

Citation: Restorative Neurology and Neuroscience, vol. 22, no. 6, pp. 421-428, 2004

Authors: Rizzo, III, Joseph F. | Goldbaum, Sumiko | Shahin, Mohamed | Denison, Timothy J. | Wyatt, John

Article Type: Research Article

Abstract: Purpose: Our primary goal was to assess the effects of varying stimulus parameters on the electrically evoked cortical potentials (EECPs) in rabbits, which we intend to use as one measure of biocompatibility of implanted retinal prosthetic devices. We also sought to exclude contamination of waveforms recorded over the occipital cortex from electrical activity from the retina and the degree of reproducibility of EECP recordings. Methods: A concentric bipolar platinum electrode or microfabricated 5 × …5 electrode array delivered current to the retina of 43 Dutch-belted rabbits while the EECP was recorded from extradural electrodes over the occipital cortex. Electroretinogram (ERG) and visual evoked cortical potential (VECP) recordings were routinely obtained. Verification that occipital cortical recordings were not heavily contaminated by electrical potentials from the retina (i.e. the "validity" of the cortical recordings) was made by recording retinal and brain responses before and after intravitreal injection of tetrodotoxin. Electrical stimulation of the retina was performed with monopolar (with distant return) or bipolar electrode configurations. Cortical responses were computer-averaged over 100–500 stimulations. The effect of variation in stimulus current, charge, duration, frequency, polarity and spatial orientation of stimulating electrodes on cortical responses was studied. Results: Progressive reduction of responses toward the anterior skull and abolition of posterior recordings by tetrodotoxin indicated that retinal activity did not significantly contaminate EECP recordings. Reproducibility testing revealed that inter-animal variability within the first hour of testing across all animals was not significantly greater than that found during prolonged testing of a single animal. The lowest current that yielded a reproducible EECP with monopolar stimulation was 75 μA (total current through 21 electrodes) using 200 μsec pulses, which yielded a 45 μV cortical response. Strength-duration curves were generally flat for fixed charge stimulation and linear for fixed current stimulation, at least up to a saturation point, which occurred at very high charge. Over 0.5–16 Hz stimulus frequencies, ERGs varied little but evoked potential responses showed a monotonic decline in amplitude at higher frequencies. Large negative-going initial pulses of a biphasic pair yielded the largest cortical amplitudes. EECP amplitudes varied significantly with the orientation of stimulating electrodes on the retina. Conclusions: This study provides novel data on the reproducibility of EECP recordings, and insight into stimulation parameters that affect retinal and cortical responses. This information can be used to improve the yield of retinal and evoked potential recor- dings, which will enhance the prospective assessment of the efficacy of stimulation and health of the stimulated tissues following. Show more

Citation: Restorative Neurology and Neuroscience, vol. 22, no. 6, pp. 429-443, 2004

Authors: Breitenstein, Caterina | Kamping, Sandra | Jansen, Andreas | Schomacher, Marion | Knecht, Stefan

Article Type: Research Article

Abstract: Purpose. Children acquire new words through exposure, without the necessity for explicit feedback by caregivers. In aphasia therapy, feedback to the patient is considered an important asset even though the empirical base demonstrating superior learning with online feedback is lacking. The present study examined if healthy adults and patients with chronic aphasia can acquire a new lexicon by intense frequency of exposure alone. Methods. We compared learning rates with "frequency of exposure alone" (no-feedback condition: …n = 19 healthy adults; two patients with chronic Broca's and Wernicke's aphasia, respectively) with a condition where subjects additionally received online feedback (feedback condition; n = 19). The learning principle was higher statistical co-occurrences of "correct" picture-pseudoword pairings as compared to "incorrect" pairings. In the feedback condition, immediate online feedback on the correctness of respective choices was additionally provided. Results. Both healthy groups successfully acquired the vocabulary. Feedback led to a slight initial acceleration of learning but did not improve latency to peak performance or long-term retention of lexical knowledge. These findings show that high frequency interactive exposure is a potent word learning mechanism in adults and that feedback is not crucial. This is further corroborated by our successful training of two patients with chronic aphasia without online feedback. Conclusions. Our findings demonstrate that word re-learning in aphasia could benefit from maximizing on the frequency of exposure and exploiting the therapeutic principle of "massed practice", which has been successful in physical rehabilitation after stroke. Additionally, economizing on feedback may prevent patients becoming discouraged by continuous confrontation with their deficits. Show more

Keywords: language acquisition, associative learning, aphasia, aphasia therapy, feedback

Citation: Restorative Neurology and Neuroscience, vol. 22, no. 6, pp. 445-458, 2004

Authors: Qu, Ting Yu | Dong, Xia Jing | Sugaya, Ikuko | Vaghani, Ankur | Pulido, Jose | Sugaya, Kiminobu

Article Type: Research Article

Abstract: Purpose: Recent reports show that marrow derived mesenchymal stem cells (MeSCs) may have the ability to differentiate into diverse cell types unrelated to their phenotypical embryonic origin, including neural cells. While demonstrated "in vitro" and neonatally, efforts to demonstrate this ability in adult animal brains have had limited success. If it can be shown that human MeSC (HMeSC) can differentiate into neural cells in adult brain, it would open up the possibility that HMeSCs may be …of potential therapeutic use in cell replacement therapies for neurological diseases. Here, we demonstrate that adult HMeSCs treated with 5-bromo-2-deoxyuridine (BrdU) for 3 weeks develop the capability to differentiate into neural and retinal cells when provided the appropriate lineage specific differentiation signals in vitro and in adult animals. HMeSC without BrdU treatment did not differentiate into neurons in vitro or adult animal or retinal cells in adult animal. Methods: MeSCs isolated from adult human bone marrow were treated with BrdU (3 μM) for 3 weeks and then subjected to differentiation conditions both in vitro and in vivo. Results: BrdU pretreated HMeSCs express neuronal and glial markers after co-culture with differentiated human neural stem cells and after transplantation into the adult rat brain. HMeSCs pretreated with BrdU and transforming growth factor-β3 express a photoreceptor marker after transplantation into the adult rat vitreous. Conclusions: These results suggest that BrdU treatment may increase the multipotency of HMeSCs for possible use in autologous cell therapies for neurological and opthamological diseases. Show more

Citation: Restorative Neurology and Neuroscience, vol. 22, no. 6, pp. 459-468, 2004

Authors: Xu, Guanghui | Li, Xiaoxia | Bai, Yun | Bai, Jinzhu | Li, Lingsong | Shen, Li

Article Type: Research Article

Abstract: Purpose: Human neural progenitor cells hold great promise for treating a variety of human neurological diseases such as spinal cord injury. One of the issues limiting this technology is how to expand neural progenitor cells in vitro to obtain sufficient number of cells for clinical transplantation. We have established a homogeneous population of human neural progenitor cells (hNPC-TERT) immortalized by the human telomerase reverse transcriptase (hTERT) gene. Then we studied whether these cells could …differentiate into neural cells in vivo and improve the recovery of spinal cord-injured rats. Methods: The hNPC-TERT cells had been transplanted into the injured spinal cord and the functional recovery of the rats with spinal cord contusion injury was evaluated through BBB locomotor scale and Motor Evoked Potentials. Additionally, the differentiation of hNPC-TERT cells was shown by immunocytochemistry. Results: As revealed by this animal model, hNPC-TERT cells developed into functional cells in the injured spinal cord and improved recovery from spinal cord injury in both locomotor scores and electrophysiological parameter in this animal model. Conclusions: This study is the first demonstration of the use of telomerase-driven human progenitor cells to treat spinal cord injury and should provide a new cell source for research of clinical application. Show more

Keywords: neural progenitor cells, transplantation, differentiation, spinal cord injury, BBB locomotor scale, motor evoked potentials

Citation: Restorative Neurology and Neuroscience, vol. 22, no. 6, pp. 469-476, 2004

Article Type: Correction

Citation: Restorative Neurology and Neuroscience, vol. 22, no. 6, pp. 477-478, 2004