Recovery after spinal cord injury by modulation of the proteoglycan receptor PTPσ

Rink, Svenja; Arnold, Dominik; Wöhler, Aliona; Bendella, Habib; Meyer, Carolin; Μanthou, Maria Eleni; Papamitsou, Theodora; Sarıkcıoğlu, Levent; Angelov, Doychin N.

doi:10.1016/j.expneurol.2018.08.003

Cited by 14 publications

(16 citation statements)

References 52 publications

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“…Enoxaparin has recently been shown to promote functional recovery after SCI by antagonizing PTPRσ (Ito et al 2021 ). Our own work in synthesizing a peptide, ISP (intracellular sigma peptide), modeled against the regulatory wedge domain of PTPRσ to “turn off” CSPG-PTPRσ signaling resulted in the rescue of the axon growth cone from becoming entrapped and dystrophic and remarkably enhanced bladder and coordinated locomotor recovery following systemic application in rat models of contusive SCI (Lang et al 2015 ; Rink et al 2018 ). Treatment of dorsal root ganglion neurons and oligodendrocyte progenitor cells (Luo et al 2018 ; Tran et al 2018a ) with ISP-induced autologous localized protease release, which was capable of immediate degradation of CSPGs to enhance process outgrowth or maturation and cell survival, respectively.…”

Section: Sci and Plasticity Of The Glial Scarmentioning

confidence: 99%

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: Sci and Plasticity Of The Glial Scarmentioning

confidence: 99%

New insights into glial scar formation after spinal cord injury

2021

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“…After SCI, reactive astrocytes upregulate expression and secretion of CSPGs, which contributes to the development of glial scar tissues. [29][30][31] Both in vitro and in vivo studies have shown inhibitory effect of CSPGs on axonal growth in neural regeneration. After spinal cord injury, the expression of neurocan, brevican, and versican increased within a few days and neurocan and versican remained elevated for four weeks post-injury.…”

Section: Discussionmentioning

confidence: 99%

“…A number of studies have demonstrated that chondroitin sulfate proteoglycans (CSPGs), which are a major component of the glial scar, are a strong inhibitory factor against axon outgrowth. [29][30][31] A previous study showed that transplantation of collagen tube grafts into transected rat spinal cord promoted astrocyte migration into the spinal cord lesion and supported axonal growth. [32] Assessment of the effect of neural conduit materials on astrocytes is essential given their important role in neural injury repair, [33] with conduits producing enhanced astrocyte migration and reduced CSPG production being desirable.…”

Section: Introductionmentioning

confidence: 99%

A Protein Composite Neural Scaffold Modulates Astrocyte Migration and Transcriptome Profile

Yao

Brice

Shippy

2022

Macromolecular Bioscience

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Bioscaffold implantation is a promising approach to facilitate the repair and regeneration of wounded neural tissue after injury to the spinal cord or peripheral nerves. However, such bioscaffold grafts currently result in only limited functional recovery. The generation of a neural scaffold using a combination of collagen and glutenin is reported. The conduit material and mechanical properties, as well as its effect on astrocyte behavior is tested. After neural injuries, astrocytes move into the lesion and participate in the process of remodeling the micro-architecture of the wounded neural tissue. In this study, human astrocytes grown on glutenin-collagen scaffolds show higher motility and a lower proliferation rate compared with those grown on collagen scaffolds. RNA sequencing reveals that astrocytes grown on the two types of scaffolds show differentially expressed genes in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways such as actin cytoskeleton and focal adhesion that regulate astrocyte migration on scaffolds. The gene expression of aggrecan and versican, chondroitin sulfate proteoglycans that inhibit axonal growth, is down-regulated in astrocytes grown on glutenin-collagen scaffolds. These outcomes indicate that the implantation of glutenin-collagen scaffolds may promote astrocyte function in the neural regeneration process by enhanced cell migration and reduced glial scar formation.

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“…ISP has very high specificity for PTPσ ( Sakamoto et al, 2019 ). Importantly, after systemic delivery, ISP rapidly enters the CNS and leads to significant axonal sprouting with restored sensory motor and bladder function after acute contusive cord injury in adult rats ( Lang et al, 2015 ; Rink et al, 2018 ) and has also led to the enhanced migration, differentiation, and remyelination by oligodendrocyte precursor cells (OPCs) with functional recovery in mouse models of MS ( Luo et al, 2018 ) and SCI ( Dyck et al, 2018 , 2019 ).…”

Section: Introductionmentioning

confidence: 99%