Restorative Neurology and Neuroscience - Volume 37, issue 6

Authors: Antal, Andrea | Sabel, Bernhard

Article Type: Editorial

DOI: 10.3233/RNN-199001

Citation: Restorative Neurology and Neuroscience, vol. 37, no. 6, pp. 523-524, 2019

Authors: Yin, Yuqin | De Lima, Silmara | Gilbert, Hui-Ya | Hanovice, Nicholas J. | Peterson, Sheri L. | Sand, Rheanna M. | Sergeeva, Elena G. | Wong, Kimberly A. | Xie, Lili | Benowitz, Larry I.

Article Type: Research Article

Abstract: The optic nerve conveys information about the outside world from the retina to multiple subcortical relay centers. Until recently, the optic nerve was widely believed to be incapable of re-growing if injured, with dire consequences for victims of traumatic, ischemic, or neurodegenerative diseases of this pathway. Over the past 10–20 years, research from our lab and others has made considerable progress in defining factors that normally suppress axon regeneration and the ability of retinal ganglion cells, the projection neurons of the retina, to survive after nerve injury. Here we describe research from our lab on the role of inflammation-derived growth …factors, suppression of inter-cellular signals among diverse retinal cell types, and combinatorial therapies, along with related studies from other labs, that enable animals with optic nerve injury to regenerate damaged retinal axons back to the brain. These studies raise the possibility that vision might one day be restored to people with optic nerve damage. Show more

Keywords: Optic nerve, axon regeneration, inflammatory cells, retina, survival, zinc chelation, brain re-innervation, vision, oncomodulin

DOI: 10.3233/RNN-190960

Citation: Restorative Neurology and Neuroscience, vol. 37, no. 6, pp. 525-544, 2019

Authors: Huang, Haoliang | Kaur, Simran | Hu, Yang

Article Type: Research Article

Abstract: Background: Permanent loss of vital functions after central nervous system (CNS) injury occurs in part because axons in the adult mammalian CNS do not regenerate after injury. PTEN was identified as a prominent intrinsic inhibitor of CNS axon regeneration about 10 years ago. The PTEN negatively regulated PI3K-AKT-mTOR pathway, which has been intensively explored in diverse models of axon injury and diseases and its mechanism for axon regeneration is becoming clearer. Objective: It is timely to summarize current knowledge about the PTEN/AKT/mTOR pathway and discuss future directions of translational regenerative research for neural injury and neurodegenerative diseases. …Methods: Using mouse optic nerve crush as an in vivo retinal ganglion cell axon injury model, we have conducted an extensive molecular dissection of the PI3K-AKT-mTORC1/mTORC2 pathway to illuminate the cross-regulating mechanisms in axon regeneration. Results: AKT is the nodal point that coordinates both positive (PI3K-PDK1-pAKT-T308) and negative (PI3K-mTORC2-pAKT-S473) signals to regulate adult CNS axon regeneration through two parallel pathways, activating mTORC1 and inhibiting GSK3β . However, mTORC1/S6K1-mediated feedback inhibition after PTEN deletion prevents potent AKT activation. Conclusions: A key permissive signal from an unidentified AKT-independent pathway is required for stimulating the neuron-intrinsic growth machinery. Future studies into this complex neuron-intrinsic balancing mechanism involving necessary and permissive signals for axon regeneration is likely to lead to safe and effective regenerative strategies for CNS repair. Show more

Keywords: Axon regeneration, PTEN, mTOR, AKT, Optic Nerve, RGC

DOI: 10.3233/RNN-190949

Citation: Restorative Neurology and Neuroscience, vol. 37, no. 6, pp. 545-552, 2019

Authors: Vaucher, Elvire | Laliberté, Guillaume | Higgins, Marie-Charlotte | Maheux, Manon | Jolicoeur, Pierre | Chamoun, Mira

Article Type: Research Article

Abstract: Background: The cholinergic system is a potent neuromodulator system that plays a critical role in cortical plasticity, attention, and learning. Recently, it was found that boosting this system during perceptual learning robustly enhances sensory perception in rodents. In particular, pairing cholinergic activation with visual stimulation increases neuronal responses, cue detection ability, and long-term facilitation in the primary visual cortex. The mechanisms of cholinergic enhancement are closely linked to attentional processes, long-term potentiation, and modulation of the excitatory/inhibitory balance. Some studies currently examine this effect in humans. Objective: The present article reviews the research from our laboratory, examining whether …potentiating the central cholinergic system could help visual perception and restoration. Methods: Electrophysiological or pharmacological enhancement of the cholinergic system are administered during a visual training. Electrophysiological responses and perceptual learning performance are investigated before and after the training in rats and humans. This approach’s ability to restore visual capacities following a visual deficit induced by a partial optic nerve crush is also investigated in rats. Results: The coupling of visual training to cholinergic stimulation improved visual discrimination and visual acuity in rats, and improved residual vision after a deficit. These changes were due to muscarinic and nicotinic transmissions and were associated with a functional improvement of evoked potentials. In humans, potentiation of cholinergic transmission with 5 mg of donepezil showed improved learning and ocular dominance plasticity, although this treatment was ineffective in augmenting the perceptual threshold and electroencephalography. Conclusions: Potential therapeutic outcomes ought to facilitate vision restoration using commercially available cholinergic agents combined with visual stimulation in order to prevent irreversible vision loss in patients. This approach has the potential to help a large population of visually impaired individuals. Show more

Keywords: Acetylcholine, attention, cholinesterase inhibitor, cholinergic system, cortical plasticity, donepezil, perceptual learning, visual cortex

DOI: 10.3233/RNN-190947

Citation: Restorative Neurology and Neuroscience, vol. 37, no. 6, pp. 553-569, 2019

Authors: Li, Hong-Ying | Rong, Sheng-Sheng | Hong, Xi | Guo, Rui | Yang, Feng-Zhen | Liang, Yi-Yao | Li, Ang | So, Kwok-Fai

Article Type: Research Article

Abstract:  Many ocular diseases (such as glaucoma, diabetic retinopathy, age-related macular degeneration, and traumatic eye injuries) can result in the degeneration of retinal cells and the subsequent loss of vision. Some kinds of treatments, such as drugs, stem cell transplantation and surgery are reported to be effective in certain patients. However, no confirmatively effective, convenient and low-price intervention has been available so far. Physical exercise has been reported to exert neuroprotective effects on several neurodegenerative diseases, including Parkinson’s disease and Alzheimer’s disease. Studies investigating the potential impacts of exercise on retinal diseases are rapidly emerging. Here we review these up-to-date findings …from both human and animal studies, and discuss the possible mechanisms underlying exercise-elicited protection on retina. Show more

Keywords: Exercise, neuroprotection, retina, microglia, oxidative stress, neurotrophic factor, adipokine, autophagy, mitochondrion

DOI: 10.3233/RNN-190945

Citation: Restorative Neurology and Neuroscience, vol. 37, no. 6, pp. 571-581, 2019

Authors: Pitchaimuthu, Kabilan | Sourav, Suddha | Bottari, Davide | Banerjee, Seema | Shareef, Idris | Kekunnaya, Ramesh | Röder, Brigitte

Article Type: Research Article

Abstract: Background: Color vision has been consistently shown to be unaffected in animals that are raised in dark or in color-deprived environments. However, there are only a few studies that directly addressed the effect of congenital visual deprivation in color perception in humans. Objective: The goal of the current study was to assess the effect of congenital visual deprivation on color vision using a panel based color arrangement test. Methods: We investigated the recovery of color vision using the Farnsworth D15 test in a group of individuals who had experienced visual deprivation since birth due to bilateral …dense congenital cataracts before undergoing cataract-reversal surgery (Congenital cataract, CC, n  = 12). In addition, we tested two groups of control participants: (1) individuals who had had non-dense congenital cataract or developed cataract later in their childhood (Developmental cataract, DC, n  = 10), and (2) sighted controls with normal or corrected to normal vision (n  = 14). Based on the methods proposed by Vingrys and King-Smith (1988) , we derived the following metrics of color vision performance: (1) total error score, (2) confusion index, (3) confusion angle, and (4) selectivity index. Results: All of the measured indices of color vision performance were unaltered by a period of congenital visual deprivation. Conclusions: Our results support the view that, development of visual functions such as color discrimination and color arrangement does not depend on typical visual experience during a sensitive phase in early childhood. Show more

Keywords: Color vision, sensitive period, congenital cataract, visual deprivation, Farnsworth D15

DOI: 10.3233/RNN-190928

Citation: Restorative Neurology and Neuroscience, vol. 37, no. 6, pp. 583-590, 2019

Authors: Werth, Reinhard

Article Type: Research Article

Abstract: Background Children are diagnosed as dyslexic when their reading performance is much below that which could be expected for their educational level and cannot be explained by a sensory, neurological or psychiatric deficit or by a low IQ. Although poor reading is a major obstacle to school and career achievement, the causes of dyslexia are unclear and traditional therapies are often unsuccessful. To determine the causes of dyslexia, experiments must demonstrate under which conditions a reading disorder occurs and whether the reading performance improves if these conditions are abolished or compensated. To avoid irreproducible results, experiments must be repeated and …the effect size must be calculated. Objectives The aims of the study were to investigate the rate and location of misread letters within pseudowords, prove the effectiveness of compensatory reading therapy and demonstrate the reproducibility of the experimental results. The influence of reading therapy on the rate of eye movements opposite to the reading direction was investigated and causes of a poor reading performance were identified. Methods The rate and location of misread letters were investigated by tachystoscopic presentation of pseudowords containing between three and six letters. Presentation time, fixation time, and the time it takes to begin pronouncing the words (speech onset latency) were changed until 95% of the pseudowords were recognized correctly. On the basis of these results, the children learned a reading strategy that compensated the causes of the reading disorder. The therapy was demonstrated to be highly effective and it was shown that the results of the therapy were reproducible. Results It was shown that misread letters occurred at all locations in pseudowords, regardless of the word's length. Inadequate fixation, excessively large saccadic amplitudes, reduced ability to simultaneously recognize a sequence of letters, a longer required fixation time and a longer required speech onset latency were all identified as causes of dyslexia. Each of the studies included in the meta-analysis were much more efficient than conventional therapeutic methods. The overall effect size with a value of Hedges' G = 1.72 showed that the therapy had a reproducible and stable effect. Conclusions The causes of dyslexia can be revealed by a dual-intervention approach consisting of a pseudoword experiment and learning a compensatory reading strategy. Reading performance improves immediately if the identified causes of dyslexia are compensated by an appropriate reading therapy. Show more

Keywords: Dyslexia, causes, reading inability, therapy, children, eye movements, simultaneous recognition

DOI: 10.3233/RNN-190939

Citation: Restorative Neurology and Neuroscience, vol. 37, no. 6, pp. 591-608, 2019

Authors: Auvray, Malika

Article Type: Research Article

Abstract: Sensory substitution devices aim at compensating sensory deficits by converting stimuli coming from a deficient sensory modality (e.g., vision) into stimuli accessible through another modality (e.g., touch or audition). Studies conducted with these devices revealed the central nervous system to be very plastic. Various laboratories have conducted studies investigating such plasticity by means of behavioural and brain-imaging techniques. At the ISIR Laboratory, we focused on the factors underlying the learning of sensory substitution devices, their adequacy to the target population, and we explored ways of improving their design by the use of crossmodal correspondences and by taking into account individual …differences in the used reference frames. We also investigated the nature of the experience with sensory substitution. In particular, we suggested moving beyond positions reducing experience to that of a single sensory modality. Rather, sensory substitution is considered as a multisensory experience, involving not only visual, but also auditory or tactile processes as well as cognitive processes. In this framework, individual differences do have an influence on the extent to which the different sensory modalities influence the experience with the devices. Show more

Keywords: Sensory substitution, blindness, brain plasticity, rehabilitation technologies, learning

DOI: 10.3233/RNN-190950

Citation: Restorative Neurology and Neuroscience, vol. 37, no. 6, pp. 609-619, 2019

Article Type: Other

Citation: Restorative Neurology and Neuroscience, vol. 37, no. 6, pp. 621-625, 2019