Scar-modulating treatments for central nervous system injury

Shen, Dingding; Wang, Xiaodong; Gu, Xiaosong

doi:10.1007/s12264-013-1456-2

Cited by 15 publications

(15 citation statements)

References 152 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Using transgenic models, researchers have gained insight into therapeutic targets that reduce the inhibitory effects of scarring on SCI repair. Targeted suppression of astrocyte signaling pathways reduces inhibitory scar formation and facilitates axon growth and SCI recovery [76]. Specifically, transgenic approaches have identified astrocyte inhibition of TGF-β/Smad, TLR, JAK/STAT3, and JNK/c-Jun signaling Resident microglia and astrocytes are activated following injury and form a glial scar surrounding and sequestering the damaged tissue (top).…”

Section: Glial and Fibrotic Scarring After Spinal Cord Injurymentioning

confidence: 99%

“…Therapeutic approaches (bold) and example agents (hyphenated) targeting glial activation, scar formation, and inflammation after spinal cord injury (bottom). This therapeutic list is not comprehensive, and references and abbreviations are in the main body of the manuscript cascades, among others, as potential SCI therapies [76]. However, depending upon the timing post-injury, astrocyte inhibition also interferes with ECM deposition of growthsupportive substrates and neurotrophins (e.g., laminin, fibronectin, growth factors) thereby reducing endogenous repair processes [77].…”

Section: Glial and Fibrotic Scarring After Spinal Cord Injurymentioning

confidence: 99%

See 1 more Smart Citation

Spinal Cord Injury Scarring and Inflammation: Therapies Targeting Glial and Inflammatory Responses

2018

View full text Add to dashboard Cite

Deficits in neuronal function are a hallmark of spinal cord injury (SCI) and therapeutic efforts are often focused on central nervous system (CNS) axon regeneration. However, secondary injury responses by astrocytes, microglia, pericytes, endothelial cells, Schwann cells, fibroblasts, meningeal cells, and other glia not only potentiate SCI damage but also facilitate endogenous repair. Due to their profound impact on the progression of SCI, glial cells and modification of the glial scar are focuses of SCI therapeutic research. Within and around the glial scar, cells deposit extracellular matrix (ECM) proteins that affect axon growth such as chondroitin sulfate proteoglycans (CSPGs), laminin, collagen, and fibronectin. This dense deposition of material, i.e., the fibrotic scar, is another barrier to endogenous repair and is a target of SCI therapies. Infiltrating neutrophils and monocytes are recruited to the injury site through glial chemokine and cytokine release and subsequent upregulation of chemotactic cellular adhesion molecules and selectins on endothelial cells. These peripheral immune cells, along with endogenous microglia, drive a robust inflammatory response to injury with heterogeneous reparative and pathological properties and are targeted for therapeutic modification. Here, we review the role of glial and inflammatory cells after SCI and the therapeutic strategies that aim to replace, dampen, or alter their activity to modulate SCI scarring and inflammation and improve injury outcomes.

show abstract

Section: Glial and Fibrotic Scarring After Spinal Cord Injurymentioning

confidence: 99%

Section: Glial and Fibrotic Scarring After Spinal Cord Injurymentioning

confidence: 99%

Spinal Cord Injury Scarring and Inflammation: Therapies Targeting Glial and Inflammatory Responses

2018

View full text Add to dashboard Cite

show abstract

“…Whereas glial scars are neuroprotective (against severe inflammation) they also inhibit axon regrowth (Frisén et al, ; Liu et al, ; Rowland, Hawryluk, Kwon, & Fehlings, ). Despite numerous efforts to reduce the negative impact of the glial scar, improvements to functional recovery remain limited (Sekiya et al, ; Shen, Wang, & Gu, ; Zhao & Fawcett, ).…”

Section: Introductionmentioning

confidence: 99%

Neural stem/progenitor cells are activated during tail regeneration in the leopard gecko (Eublepharis macularius)

Gilbert

Vickaryous

2017

J of Comparative Neurology

View full text Add to dashboard Cite

As for many lizards, the leopard gecko (Eublepharis macularius) can self-detach its tail to avoid predation and then regenerate a replacement. The replacement tail includes a regenerated spinal cord with a simple morphology: an ependymal layer surrounded by nerve tracts. We hypothesized that cells within the ependymal layer of the original spinal cord include populations of neural stem/progenitor cells (NSPCs) that contribute to the regenerated spinal cord. Prior to tail loss, we performed a bromodeoxyuridine pulse-chase experiment and found that a subset of ependymal layer cells (ELCs) were label-retaining after a 140-day chase period. Next, we conducted a detailed spatiotemporal characterization of these cells before, during, and after tail regeneration. Our findings show that SOX2, a hallmark protein of NSPCs, is constitutively expressed by virtually all ELCs before, during, and after regeneration. We also found that during regeneration, ELCs express an expanded panel of NSPC and lineage-restricted progenitor cell markers, including MSI-1, SOX9, and TUJ1. Using electron microscopy, we determined that multiciliated, uniciliated, and biciliated cells are present, although the latter was only observed in regenerated spinal cords. Our results demonstrate that cells within the ependymal layer of the original, regenerating and fully regenerate spinal cord represent a heterogeneous population. These include radial glia comparable to Type E and Type B cells, and a neuronal-like population of cerebrospinal fluid-contacting cells. We propose that spinal cord regeneration in geckos represents a truncation of the restorative trajectory observed in some urodeles and teleosts, resulting in the formation of a structurally distinct replacement.

show abstract

“…The alternative to nerve suture is biological glue which was more effective than traditional stitches when connecting stumps [126,127]. Efforts were also made to combat the growth of collagen in sutures and nerve neuromas [128][129][130]. Attempts to prevent the emergence of diastase by stitching stump not "end-to-end" but "side-to-side" or "side-to-end" had no significant effect in increasing and accelerating recovery [131,132].…”

Section: Chapter 4 Nerve Fiber Trauma and The Retraction Of Axoplasmmentioning

confidence: 99%

“…Our experiments indicate the possibility of a new approach in the treatment of postoperative nerve transection. Attempts to deal with post-traumatic scar in the nerves and brain, had previously made use of numerous inhibitors of collagen formation and cell transplantation [128,130], but the role of the retraction of the fibers in the expansion of diastase apparently remains unexplored.…”

Section: Chapter 4 Nerve Fiber Trauma and The Retraction Of Axoplasmmentioning

confidence: 99%

Properties Live Axoplasm

2015

Single Cell Biol

View full text Add to dashboard Cite

This book is devoted to the study of physiological properties of a living axoplasm, which, as it turns out, is rarely studied as a single organ. This study revealed a number her new physiological properties. The mechanism of simultaneous currents, bidirectional axoplasm, disappearance streams and reappearance of the apical dendrites of pyramidal neurons in the brain during stress were revealed, as well as the causes of the similarity of nerve terminals regardless of their very different physiological functions. There exists proof of differences in presynaptic terminals of the postsynaptic. The reasons for the impossibility of treating transected axons using surgical sutures are discussed, and finally the cause of the absence of swelling properties in myelinated fibers with hypotension environment is solved. Some new approaches to the treatment of fibers, early manifestations of diastase nonspecific reactions,and Schmidt-Lanterman clefts.

show abstract

Scar-modulating treatments for central nervous system injury

Cited by 15 publications

References 152 publications

Spinal Cord Injury Scarring and Inflammation: Therapies Targeting Glial and Inflammatory Responses

Spinal Cord Injury Scarring and Inflammation: Therapies Targeting Glial and Inflammatory Responses

Neural stem/progenitor cells are activated during tail regeneration in the leopard gecko (Eublepharis macularius)

Properties Live Axoplasm

Contact Info

Product

Resources

About