Compression Decreases Anatomical and Functional Recovery and Alters Inflammation after Contusive Spinal Cord Injury

Orr, Michael B.; Simkin, Jennifer; Bailey, William M.; Kadambi, Neha S; McVicar, Anna Leigh; Veldhorst, Amy K.; Gensel, John C.

doi:10.1089/neu.2016.4915

Cited by 24 publications

(14 citation statements)

References 47 publications

(75 reference statements)

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“…Scarring and inflammatory responses to SCI include a complex diversity of cells and cellular activities that vary based on injury type, timing, and spatial distribution [182,183]. Glial and inflammatory cells affect the injury progression with profound impacts on overall neuronal function and SCI outcomes.…”

Section: Resultsmentioning

confidence: 99%

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

2018

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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.

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Section: Resultsmentioning

confidence: 99%

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

2018

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“…Although it has not been identified as a myelin receptor in SCI, we recently observed that macrophages upregulate MARCO in response to proinflammatory stimuli and express MARCO in the injured spinal cord (Gensel, Kopper, Zhang, Orr, & Bailey, 2017;Orr et al, 2017).…”

Section: A Cr Op H Ag E R Ec Ep Tor -M Ed I At Ed M Y El I N R E mentioning

confidence: 89%

“…Thus, it is likely that MARCO can bind myelin lipids effectively. Although it has not been identified as a myelin receptor in SCI, we recently observed that macrophages upregulate MARCO in response to proinflammatory stimuli and express MARCO in the injured spinal cord (Gensel, Kopper, Zhang, Orr, & Bailey, ; Orr et al, ). MARCO activation, therefore, may be a potential mechanism for proinflammatory macrophage‐mediated myelin removal in SCI.…”

Section: Macrophage Receptor–mediated Myelin Removalmentioning

confidence: 99%

Myelin as an inflammatory mediator: Myelin interactions with complement, macrophages, and microglia in spinal cord injury

Kopper

Gensel

2017

J of Neuroscience Research

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Spinal cord injury (SCI) triggers chronic intraspinal inflammation consisting of activated resident and infiltrating immune cells (especially microglia/macrophages). The environmental factors contributing to this protracted inflammation are not well understood, however, myelin lipid debris is a hallmark of SCI. Myelin is also a potent macrophage stimuli and target of complement-mediated clearance and inflammation. The downstream effects of these neuro-immune interactions have the potential to contribute to ongoing pathology or facilitate repair. This depends in large part on whether myelin drives pathological or reparative macrophage activation states, commonly referred to as M1 (pro-inflammatory) or M2 (alternatively) macrophages respectively. Here we review the processes by which myelin debris may be cleared through macrophage surface receptors and the complement system, how this differentially influences macrophage and microglial activation states, and how the cellular functions of these myelin macrophages and complement proteins contribute to chronic inflammation and secondary injury after SCI.

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“…Spinal cord injury (SCI) causes serious disability and is a medical problem worldwide (1). SCI has two defined phases, consisting of primary and secondary injury mechanisms that lead to an excessive inflammatory response (2,3). Disruption of the spinal tract results in neuronal apoptosis, and impedes neuronal repair and regeneration.…”

Section: Introductionmentioning

confidence: 99%

Bone marrow stromal cells improved functional recovery in spinal cord injury rats partly via the Toll‑like receptor‑4/nuclear factor‑κB signaling pathway

Bai

Zhou

2018

Exp Ther Med

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Spinal cord injury (SCI) results in inflammation, and TLR4, which is an inflammatory factor, has an important role in the pathological injury that occurs following SCI. Recently, bone marrow stromal cells (BMSCs) have been demonstrated to be a novel treatment in SCI. However, the underlying mechanism of neuroprotection in SCI by BMSCs remains unclear. The present study was designed to investigate the therapeutic mechanism of BMSCs in SCI by analysis of Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) expression. The present results demonstrated that BMSC transplantation promoted functional recovery and tissue repair in SCI rats. Interestingly, it also reduced the expression of TLR4 and NF-κB after SCI. Furthermore, it was demonstrated that BMSCs downregulated the expression of apoptosis factor caspase-12 in the SCI rat model. The present results demonstrated that BMSCs may have incorporated into the spinal cord to improve locomotor function after SCI, partly via the TLR4/NF-κB signaling pathway. To the best of our knowledge, this is the first study to determine that BMSCs prevented secondary injury and enhanced functional recovery in SCI via inhibition of TLR4/NF-κB-mediated inflammation.

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Compression Decreases Anatomical and Functional Recovery and Alters Inflammation after Contusive Spinal Cord Injury

Cited by 24 publications

References 47 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

Myelin as an inflammatory mediator: Myelin interactions with complement, macrophages, and microglia in spinal cord injury

Bone marrow stromal cells improved functional recovery in spinal cord injury rats partly via the Toll‑like receptor‑4/nuclear factor‑κB signaling pathway

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