Dissecting the Dual Role of the Glial Scar and Scar-Forming Astrocytes in Spinal Cord Injury

Yang, Tuo; Dai, YuJuan; Chen, Gang; Cui, Shusen

doi:10.3389/fncel.2020.00078

Cited by 129 publications

(135 citation statements)

References 132 publications

(190 reference statements)

Supporting

Mentioning

133

Contrasting

Unclassified

Order By: Relevance

“…It should be pointed out that at day 60 multiple macrophages were still present in the defect site. These findings definitely prove that rearrangement processes occur continuously in the process of maturation of a glial scar [12,17]. Neoangiogenesis in the peripheral portion of the defect was already noticeable by day 5.…”

supporting

confidence: 65%

A new model of spinal cord injury by cryoapplication: Morphodynamics of histological changes of the spinal cord lesion

Telegin

Minakov

Chernov

et al. 2020

Preprint

View full text Add to dashboard Cite

Up to 500,000 people worldwide suffer from spinal cord injuries (SCI) annually, according to the WHO. Animal models are essential for searching novel methodological guidelines and therapeutic agents for SCI treatment. We developed an original model of posttraumatic spinal cord glial scar in rats using cryoapplication. The method is based on cryodestruction of spinal cord tissue with liquid nitrogen. Thirty six male SD linear rats of SPF category were included in this experimental study. A T13 unilateral hemilaminectomy was performed with an operating microscope, as it was extremely important not to penetrate the dura mater, and liquid nitrogen was applied into the bone defect for one minute. The animals were euthanized at various intervals ranging from 1 to 60 days after inducing cryogenic trauma, their Th12-L1 vertebrae were removed “en bloc” and the segment of the spinal cord exposed to the cryoapplicator was carefully separated for histological examination. The study results demonstrated that cryoapplication of liquid nitrogen, provoking a local temperature of approximately minus 20°C, produced a highly standardized transmural defect which extended throughout the dorsoventral arrangement of the spinal cord and had an “hour-glass” shape. During the entire study period (1-60 post-injury days), the glial scarring process and the spinal cord defect were located within the surgically approached vertebral space (Th13). Unlike other available experimental models of SCI (compression, contusion, chemical, etc.), the present option is characterized by a minimal invasiveness (the hemilaminectomy is less than 1 mm wide), high precision and consistency. Also, there was a low interanimal variability in histological lesions and dimensions of the produced defect. The original design of cryoapplicator used in the study played a major role in achieving these results. The original technique of high-precision cryoapplication for inducing consistent morphodynamic glial scarring could facilitate a better understanding of the self-recovery processes of injured spinal cord and would be helpful for proposing new platforms for the development of therapeutic strategies.

show abstract

supporting

confidence: 65%

A new model of spinal cord injury by cryoapplication: Morphodynamics of histological changes of the spinal cord lesion

Telegin

Minakov

Chernov

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Glial scar formation begins early after SCI and can be considered mature after some weeks (from two to several weeks) [ 21 ]. To evaluate the BoNT/A effect on mature glial scar surrounding the core lesion and reactive astrocytes adjacent to neural tissue, we analyzed glial fibrillary acidic protein (GFAP) expression 30 days after SCI in spinal sections at different levels: from the core lesion (T10) toward peri-lesioned (T9–T11) and distal (rostral: T2–T5 or caudal: L1–L3) areas ( Figure 3 A).…”

Section: Resultsmentioning

confidence: 99%

Revealing the Therapeutic Potential of Botulinum Neurotoxin Type A in Counteracting Paralysis and Neuropathic Pain in Spinally Injured Mice

Vacca

Madaro

Angelis

et al. 2020

Toxins

View full text Add to dashboard Cite

Botulinum neurotoxin type A (BoNT/A) is a major therapeutic agent that has been proven to be a successful treatment for different neurological disorders, with emerging novel therapeutic indications each year. BoNT/A exerts its action by blocking SNARE complex formation and vesicle release through the specific cleavage of SNAP-25 protein; the toxin is able to block the release of pro-inflammatory molecules for months after its administration. Here we demonstrate the extraordinary capacity of BoNT/A to neutralize the complete paralysis and pain insensitivity induced in a murine model of severe spinal cord injury (SCI). We show that the toxin, spinally administered within one hour from spinal trauma, exerts a long-lasting proteolytic action, up to 60 days after its administration, and induces a complete recovery of muscle and motor function. BoNT/A modulates SCI-induced neuroglia hyperreactivity, facilitating axonal restoration, and preventing secondary cells death and damage. Moreover, we demonstrate that BoNT/A affects SCI-induced neuropathic pain after moderate spinal contusion, confirming its anti-nociceptive action in this kind of pain, as well. Our results provide the intriguing and real possibility to identify in BoNT/A a therapeutic tool in counteracting SCI-induced detrimental effects. Because of the well-documented BoNT/A pharmacology, safety, and toxicity, these findings strongly encourage clinical translation.

show abstract

“…These miRNAs are all regulators of glial scar formation, which first requires the initiation of reactive astrogliosis and subsequent astrocyte proliferation at the lesion site. The scar then matures—at which point, proliferation and reactive astrogliosis are tempered back down [ 100 ]. Decreased miR-99a/143 boosts local astrocyte proliferation and miR-145 inhibits astrogliosis, miR-449 attenuates scar formation, and miR-125a promotes astrogliosis [ 32 ].…”

Section: Contribution Of Mirnas To Remyelination In Cns Cellsmentioning

confidence: 99%

The Role of MicroRNAs in Repair Processes in Multiple Sclerosis

Duffy

McCoy

2020

Cells

View full text Add to dashboard Cite

Multiple sclerosis (MS) is an autoimmune disorder characterised by demyelination of central nervous system neurons with subsequent damage, cell death and disability. While mechanisms exist in the CNS to repair this damage, they are disrupted in MS and currently there are no treatments to address this deficit. In recent years, increasing attention has been paid to the influence of the small, non-coding RNA molecules, microRNAs (miRNAs), in autoimmune disorders, including MS. In this review, we examine the role of miRNAs in remyelination in the different cell types that contribute to MS. We focus on key miRNAs that have a central role in mediating the repair process, along with several more that play either secondary or inhibitory roles in one or more aspects. Finally, we consider the current state of miRNAs as therapeutic targets in MS, acknowledging current challenges and potential strategies to overcome them in developing effective novel therapeutics to enhance repair mechanisms in MS.

show abstract

Dissecting the Dual Role of the Glial Scar and Scar-Forming Astrocytes in Spinal Cord Injury

Cited by 129 publications

References 132 publications

A new model of spinal cord injury by cryoapplication: Morphodynamics of histological changes of the spinal cord lesion

A new model of spinal cord injury by cryoapplication: Morphodynamics of histological changes of the spinal cord lesion

Revealing the Therapeutic Potential of Botulinum Neurotoxin Type A in Counteracting Paralysis and Neuropathic Pain in Spinally Injured Mice

The Role of MicroRNAs in Repair Processes in Multiple Sclerosis

Contact Info

Product

Resources

About