Textbook of Neural Repair and Rehabilitation

New treatments that can facilitate neural repair and reduce persistent impairments have significant value in promoting recovery following stroke. One technique that has gained interest is transcranial direct current stimulation (tDCS) as early research suggested it could enhance plasticity and enable greater behavioral recovery. However, several studies have now identified substantial inter-subject variability in response to tDCS and clinical trials revealed insufficient evidence of treatment effectiveness. A possible explanation for the varied and negative findings is that the physiological model of stroke recovery that researchers have used to guide the application of tDCS based treatments in stroke is overly simplistic and does not account for stroke heterogeneity or known determinants that affect the tDCS response. Here, we propose that tDCS could have a more clearly beneficial role in enhancing stroke recovery if greater consideration is given to individualizing treatment. By critically reviewing the proposed mechanisms of tDCS, stroke physiology across the recovery continuum, and known determinants of tDCS response, we propose a new, theoretical, patient-tailored approach to delivering tDCS after stroke. The proposed model includes a step-by-step principled selection strategy for identifying optimal neuromodulation targets and outlines key areas for further investigation. Tailoring tDCS treatment to individual neuroanatomy and physiology is likely our best chance at producing robust and meaningful clinical benefit for people with stroke and would, therefore, accelerate opportunities for clinical translation.

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miR-615 Fine-Tunes Growth and Development and Has a Role in Cancer and in Neural Repair

Cells ◽

10.3390/cells9071566 ◽

2020 ◽

Vol 9 (7) ◽

pp. 1566 ◽

Cited By ~ 1

Author(s):

Marisol Godínez-Rubí ◽

Daniel Ortuño-Sahagún

Keyword(s):

Growth And Development ◽

Target Genes ◽

Noncoding Rnas ◽

Tumor Promoter ◽

Neural Repair ◽

Small Noncoding Rnas ◽

Physiological Processes ◽

And Migration ◽

Migration Of Cells ◽

Regulation Of Growth

MicroRNAs (miRNAs) are small noncoding RNAs that function as epigenetic modulators regulating almost any gene expression. Similarly, other noncoding RNAs, as well as epigenetic modifications, can regulate miRNAs. This reciprocal interaction forms a miRNA-epigenetic feedback loop, the deregulation of which affects physiological processes and contributes to a great diversity of diseases. In the present review, we focus on miR-615, a miRNA highly conserved across eutherian mammals. It is involved not only during embryogenesis in the regulation of growth and development, for instance during osteogenesis and angiogenesis, but also in the regulation of cell growth and the proliferation and migration of cells, acting as a tumor suppressor or tumor promoter. It therefore serves as a biomarker for several types of cancer, and recently has also been found to be involved in reparative processes and neural repair. In addition, we present the pleiad of functions in which miR-615 is involved, as well as their multiple target genes and the multiple regulatory molecules involved in its own expression. We do this by introducing in a comprehensible way the reported knowledge of their actions and interactions and proposing an integral view of its regulatory mechanisms.

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Axon Regeneration in the Mammalian Optic Nerve

Annual Review of Vision Science ◽

10.1146/annurev-vision-022720-094953 ◽

2020 ◽

Vol 6 (1) ◽

pp. 195-213

Author(s):

Philip R. Williams ◽

Larry I. Benowitz ◽

Jeffrey L. Goldberg ◽

Zhigang He

Keyword(s):

Optic Nerve ◽

Ganglion Cells ◽

Traumatic Injury ◽

Optic Glioma ◽

Retinal Ganglion ◽

Degenerative Diseases ◽

Nerve Crush ◽

Neural Repair ◽

Molecular Logic ◽

Injury Models

The damage or loss of retinal ganglion cells (RGCs) and their axons accounts for the visual functional defects observed after traumatic injury, in degenerative diseases such as glaucoma, or in compressive optic neuropathies such as from optic glioma. By using optic nerve crush injury models, recent studies have revealed the cellular and molecular logic behind the regenerative failure of injured RGC axons in adult mammals and suggested several strategies with translational potential. This review summarizes these findings and discusses challenges for developing clinically applicable neural repair strategies.

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Neural Repair in Stroke

Cell Transplantation ◽

10.1177/0963689719863784 ◽

2019 ◽

Vol 28 (9-10) ◽

pp. 1123-1126 ◽

Cited By ~ 4

Author(s):

Nikolas G. Toman ◽

Andrew W. Grande ◽

Walter C. Low

Keyword(s):

Stem Cells ◽

Neural Progenitor Cells ◽

Neuronal Cells ◽

Embryonic Stem ◽

Fetal Brain ◽

Neurological Deficits ◽

Experimental Stroke ◽

Neural Repair ◽

Cell Therapies ◽

Blood Stem Cells

This article reviews the progress that has been made in the development of cell therapies for the repair of nervous system damage caused by strokes, since the first report on the use of cell transplants in animal models of ischemic brain injury in 1988. At that time neural progenitor cells derived from fetal brain tissue were used as sources of cells to replace specific subsets of neuronal cells that were lost in various regions of the brain following experimentally induced strokes. Since 1988, cells from other sources, such as embryonic stem cells and inducible pluripotent stem cells, have been investigated for their ability to replace neuronal cells and repair the damaged brain. Most recently, mesenchymal stem cells and cord blood stem cells have been studied for the ability to modulate the immune system and ameliorate the neuropathology and neurological deficits associated with experimental stroke. The preclinical investigation of different cell therapy approaches for treating stroke during the past three decades has now led to many ongoing clinical trials, with the clinical evaluation of stem cell therapies for stroke now involving global participants.

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