Corrigendum: 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.2020.00270

Cited by 6 publications

(5 citation statements)

References 1 publication

(1 reference statement)

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“…It should be pointed out that at day 60 multiple macrophages were still present in the lesion. These findings prove that the rearrangement processes occur continuously in the course of glial scar formation (12,23). Beginning from day 14, connective tissue was clearly visualized in the lesion.…”

Section: Discussionsupporting

confidence: 67%

A New Precision Minimally Invasive Method of Glial Scar Simulation in the Rat Spinal Cord Using Cryoapplication

et al. 2021

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According to the World Health Organization, every year worldwide up to 500,000 people suffer a spinal cord injury (SCI). Various animal biomodels are essential for searching for novel protocols and therapeutic approaches for SCI treatment. We have developed an original model of post-traumatic spinal cord glial scarring in rats through cryoapplication. With this method the low-temperature liquid nitrogen is used for the cryodestruction of the spinal cord tissue. Forty-five Sprague Dawley (SD) non-linear male rats of the Specific-pathogen-free (SPF) category were included in this experimental study. A Th13 unilateral hemilaminectomy was performed with dental burr using an operating microscope. A specifically designed cryogenic probe was applied to the spinal cord for one minute through the created bone defect. The animals were euthanized at different time points ranging from 1 to 60 days after cold-induced injury. Their Th12-L1 vertebrae with the injured spinal cord region were removed “en bloc” for histological examination. Our data demonstrate that cryoapplication producing a topical cooling around−20°C, caused a highly standardized transmural lesion of the spinal cord in the dorsoventral direction. The lesion had an “hour-glass” shape on histological sections. During the entire study period (days 1-60 of the post-trauma period), the necrotic processes and the development of the glial scar (lesion evolution) were contained in the surgically approached vertebral space (Th13). Unlike other known experimental methods of SCI simulation (compression, contusion, etc.), the proposed technique is characterized by minimal invasiveness, high precision, and reproducibility. Also, histological findings, lesion size, and postoperative clinical course varied only slightly between different animals. An original design of the cryoprobe used in the study played a primary role in the achieving of these results. The spinal cord lesion's detailed functional morphology is described at different time points (1–60 days) after the produced cryoinjury. Also, changes in the number of macrophages at distinct time points, neoangiogenesis and the formation of the glial scar's fibrous component, including morphodynamic characteristics of its evolution, are analyzed. The proposed method of cryoapplication for inducing reproducible glial scars could facilitate a better understanding of the self-recovery processes in the damaged spinal cord. It would be evidently helpful for finding innovative approaches to the SCI treatment.

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Section: Discussionsupporting

confidence: 67%

A New Precision Minimally Invasive Method of Glial Scar Simulation in the Rat Spinal Cord Using Cryoapplication

et al. 2021

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“…In traumatic CNS injury, it has been controversial whether scar‐forming reactive astrocytes are detrimental or beneficial. First, regarding scar formation as a detrimental symptom, the widespread view on the scar‐forming reactive astrocytes is that glial scar primarily acts as a mechanical barrier to prevent axon regeneration of injured neurons (Yang et al, 2020). It is known that the proliferating scar‐forming reactive astrocytes form fences and isolate the damaged region from the relatively distant viable brain tissue.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of monoamine oxidase B prevents reactive astrogliosis and scar formation in stab wound injury model

Chun

Lim

Park

et al. 2021

Glia

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Reactive astrocytes manifest molecular, structural, and functional alterations under various pathological conditions. We have previously demonstrated that the reactive astrocytes of the stab wound injury model (STAB) display aberrant cellular gamma‐aminobutyric acid (GABA) content and tonic GABA release, whereas the active astrocytes under enriched environment (EE) express high levels of proBDNF. However, the role of monoamine oxidase B (MAO‐B) in reactive astrogliosis and hypertrophy still remains unknown. Here, we investigate the role of MAO‐B, a GABA‐producing enzyme, in reactive astrogliosis in STAB. We observed that the genetic removal of MAO‐B significantly reduced the hypertrophy, scar formation, and GABA production of reactive astrocytes, whereas the MAO‐B overexpression under glial fibrillary acidic protein (GFAP) promoter enhanced the levels of GFAP and GABA. Furthermore, we found that one of the by‐products of the MAO‐B action, H2O2, but not GABA, was sufficient and necessary for the hypertrophy of reactive astrocytes. Notably, we identified two potent pharmacological tools to attenuate scar‐forming astrogliosis—the recently developed reversible MAO‐B inhibitor, KDS2010, and an H2O2 scavenger, crisdesalazine (AAD‐2004). Our results implicate that inhibiting MAO‐B activity has dual beneficial effects in preventing astrogliosis and scar‐formation under brain injury, and that the MAO‐B/H2O2 pathway can be a useful therapeutic target with a high clinical potential.

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“…During the process of tissue cavitation, reactive astrocytes proliferate in viable tissue, gradually defining the cavity [ 11 ]. By 14-days post-stroke, this tissue edge, characterized by proliferating and reactive astrocytes, remains rather mesh-like, with macrophages migrating through this microenvironment to remove ECM remnants [ 38 ]. Infiltration of macrophages into the ECM hydrogel at this time point, therefore, is not much impacted by the microenvironment at the edge of viable brain tissue.…”

Section: Discussionmentioning

confidence: 99%

Post-Stroke Timing of ECM Hydrogel Implantation Affects Biodegradation and Tissue Restoration

Damian

Ghuman

Mauney

et al. 2021

IJMS

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Extracellular matrix (ECM) hydrogel promotes tissue regeneration in lesion cavities after stroke. However, a bioscaffold’s regenerative potential needs to be considered in the context of the evolving pathological environment caused by a stroke. To evaluate this key issue in rats, ECM hydrogel was delivered to the lesion core/cavity at 7-, 14-, 28-, and 90-days post-stroke. Due to a lack of tissue cavitation 7-days post-stroke, implantation of ECM hydrogel did not achieve a sufficient volume and distribution to warrant comparison with the other time points. Biodegradation of ECM hydrogel implanted 14- and 28-days post-stroke were efficiently (80%) degraded by 14-days post-bioscaffold implantation, whereas implantation 90-days post-stroke revealed only a 60% decrease. Macrophage invasion was robust at 14- and 28-days post-stroke but reduced in the 90-days post-stroke condition. The pro-inflammation (M1) and pro-repair (M2) phenotype ratios were equivalent at all time points, suggesting that the pathological environment determines macrophage invasion, whereas ECM hydrogel defines their polarization. Neural cells (neural progenitors, neurons, astrocytes, oligodendrocytes) were found at all time points, but a 90-days post-stroke implantation resulted in reduced densities of mature phenotypes. Brain tissue restoration is therefore dependent on an efficient delivery of a bioscaffold to a tissue cavity, with 28-days post-stroke producing the most efficient biodegradation and tissue regeneration, whereas by 90-days post-stroke, these effects are significantly reduced. Improving our understanding of how the pathological environment influences biodegradation and the tissue restoration process is hence essential to devise engineering strategies that could extend the therapeutic window for bioscaffolds to repair the damaged brain.

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

Cited by 6 publications

References 1 publication

A New Precision Minimally Invasive Method of Glial Scar Simulation in the Rat Spinal Cord Using Cryoapplication

A New Precision Minimally Invasive Method of Glial Scar Simulation in the Rat Spinal Cord Using Cryoapplication

Inhibition of monoamine oxidase B prevents reactive astrogliosis and scar formation in stab wound injury model

Post-Stroke Timing of ECM Hydrogel Implantation Affects Biodegradation and Tissue Restoration

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