Reactive Astrogliosis: Implications in Spinal Cord Injury Progression and Therapy

Li, Xinyu; Li, Meng; Tian, Lijie; Chen, Jianan; Ning, Bin

doi:10.1155/2020/9494352

Cited by 106 publications

(90 citation statements)

References 145 publications

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“…Immature microglial cell transplantation into the injured adult spinal cord also improved wound healing without scar and permitted axonal regeneration beyond the lesion (Li et al 2020b). Li et al (2020a, b) emphasize the importance of proteases in scar formation. In the neonate, microglia produce endogenous proteinase inhibitors to promote healing.…”

Section: The Biology and Transcriptomic Changes Of Microglia After Injurymentioning

confidence: 97%

New insights into glial scar formation after spinal cord injury

2021

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Severe spinal cord injury causes permanent loss of function and sensation throughout the body. The trauma causes a multifaceted torrent of pathophysiological processes which ultimately act to form a complex structure, permanently remodeling the cellular architecture and extracellular matrix. This structure is traditionally termed the glial/fibrotic scar. Similar cellular formations occur following stroke, infection, and neurodegenerative diseases of the central nervous system (CNS) signifying their fundamental importance to preservation of function. It is increasingly recognized that the scar performs multiple roles affecting recovery following traumatic injury. Innovative research into the properties of this structure is imperative to the development of treatment strategies to recover motor function and sensation following CNS trauma. In this review, we summarize how the regeneration potential of the CNS alters across phyla and age through formation of scar-like structures. We describe how new insights from next-generation sequencing technologies have yielded a more complex portrait of the molecular mechanisms governing the astrocyte, microglial, and neuronal responses to injury and development, especially of the glial component of the scar. Finally, we discuss possible combinatorial therapeutic approaches centering on scar modulation to restore function after severe CNS injury.

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Section: The Biology and Transcriptomic Changes Of Microglia After Injurymentioning

confidence: 97%

New insights into glial scar formation after spinal cord injury

2021

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“…The scar has traditionally been viewed to inhibit neurite outgrowth and axonal regeneration. The characteristic of growth inhibitory factor secretion by reactive astrocytes serves as a hindrance to axonal extensions, which deters CNS function recovery at a chronic stage [ 156 , 157 ]. A number of studies consider glial scar formation and reactive gliosis as maladaptive responses; therefore blocking its formation may be beneficial.…”

Section: Astrocyte Activation and Glial Scar Formationmentioning

confidence: 99%

Astrocyte Activation in Neurovascular Damage and Repair Following Ischaemic Stroke

Patabendige

Singh

Jenkins

et al. 2021

IJMS

125

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Transient or permanent loss of tissue perfusion due to ischaemic stroke can lead to damage to the neurovasculature, and disrupt brain homeostasis, causing long-term motor and cognitive deficits. Despite promising pre-clinical studies, clinically approved neuroprotective therapies are lacking. Most studies have focused on neurons while ignoring the important roles of other cells of the neurovascular unit, such as astrocytes and pericytes. Astrocytes are important for the development and maintenance of the blood–brain barrier, brain homeostasis, structural support, control of cerebral blood flow and secretion of neuroprotective factors. Emerging data suggest that astrocyte activation exerts both beneficial and detrimental effects following ischaemic stroke. Activated astrocytes provide neuroprotection and contribute to neurorestoration, but also secrete inflammatory modulators, leading to aggravation of the ischaemic lesion. Astrocytes are more resistant than other cell types to stroke pathology, and exert a regulative effect in response to ischaemia. These roles of astrocytes following ischaemic stroke remain incompletely understood, though they represent an appealing target for neurovascular protection following stroke. In this review, we summarise the astrocytic contributions to neurovascular damage and repair following ischaemic stroke, and explore mechanisms of neuroprotection that promote revascularisation and neurorestoration, which may be targeted for developing novel therapies for ischaemic stroke.

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“…These reactive astrocytes migrate toward the epicenter of the lesion and have an impact on the process of tissue recovery. However, ultimately they turn into scar astrocytes and form s glial scar, which produces axonal growth inhibitors and prevents axonal regeneration (25,26). We demonstrated that after the cryoinjury, the reactive astroglia was present in the lesion as early as day 7 and remained there up to day 60.…”

Section: Discussionmentioning

confidence: 81%

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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Reactive Astrogliosis: Implications in Spinal Cord Injury Progression and Therapy

Cited by 106 publications

References 145 publications

New insights into glial scar formation after spinal cord injury

New insights into glial scar formation after spinal cord injury

Astrocyte Activation in Neurovascular Damage and Repair Following Ischaemic Stroke

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

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