Stromal cell-derived factor-1 alpha (SDF-1α) improves neural recovery after spinal cord contusion in rats

Zendedel, Adib; Nobakht, Maliheh; Bakhtiyari, Mehrdad; Beyer, Cordian; Kipp, Markus; Baazm, Maryam; Joghataie, Mohammad Taghi

doi:10.1016/j.brainres.2012.07.037

Cited by 34 publications

(29 citation statements)

References 62 publications

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“…Spinal contusion lesions were made in accordance with the weight compression method [17]. This procedure has been previously described in detail [14]. Briefly, rats were anesthetized with 2.5 % isoflurane in O 2 (Abbott, Germany), and the appropriate narcosis was controlled by reflex testing such as the absence of a pedal withdrawal response to a hard pinch.…”

Section: Animals and Surgerymentioning

confidence: 99%

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Activation and Regulation of NLRP3 Inflammasome by Intrathecal Application of SDF-1a in a Spinal Cord Injury Model

et al. 2015

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Stromal cell-derived factor-1 alpha (SDF-1a) or CXCL12 is an important cytokine with multiple functions in the brain during development and in adulthood. The inflammatory response initiated by spinal cord injury (SCI) involves the processing of interleukin-1beta (IL-1ß) and IL-18 mediated by caspase-1 which is under the control of an intracellular multiprotein complex termed inflammasome. Using an SCI rat model, we found improved functional long-term recovery which is paralleled by a reduction of apoptosis after intrathecal treatment with SDF-1a. An intriguing aspect is that SDF-1a changed the number of neuroinflammatory cells in the damaged area. We further examined the cellular localization and sequential expression of several inflammasomes during SCI at 6 h, 24 h, 3 days, and 7 days as well as the role of SDF-1a as a regulatory factor for inflammasomes. Using 14-week old male Wistar rats, spinal cord contusion was applied at the thoracic segment 9, and animals were subsequently treated with SDF-1a via intrathecal application through an osmotic pump. SCI temporally increased the expression of the inflammasomes NLRP3, ASC, the inflammatory marker tumor necrosis factor-a (TNF-a), interleukin-1ß (IL-1β) and IL-18. SDF-1a significantly reduced the levels of IL-18, IL-1b, TNF-a, NLRP3, ASC, and caspase-1. Immunofluorescence double-labeling demonstrated that microglia and neurons are major sources of the ASC and NLRP3 respectivley. Our data provide clear evidence that SCI stimulates a complex scenario of inflammasome activation at the injured site and that SDF-1a-mediated neuroprotection presumably depends on the attenuation of the inflammasome complex.

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Section: Animals and Surgerymentioning

confidence: 99%

“…In a previous study, we were able to demonstrate that SDF1a exerts neuroprotective effects after SCI [14]. SDF-1a significantly alleviated neuronal damage and stimulated functional recovery in a dose-dependent way.…”

Section: Introductionmentioning

confidence: 96%

Activation and Regulation of NLRP3 Inflammasome by Intrathecal Application of SDF-1a in a Spinal Cord Injury Model

et al. 2015

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“…Unfortunately, SCI-induced disabilities that are observed in humans often are more substantial, which can limit the ability to translate treatments from animal models of SCI to clinically meaningful outcomes (Metz et al, 2000;Somers, 2000). In laboratories across the world, intervention strategies for SCI emphasize four major mechanisms for improving outcomes, including retraining motor abilities, replacing lost tissue, regenerating damaged connections, and/or retaining tissue from necrosis during the propagation of secondary injuries that occur following trauma (Alluin et al, 2014;Taylor, Jones, Tuszynski, & Blesch, 2006;Yasuda et al, 2011;Zendedel et al, 2012). Stem cell therapies show promise as a treatment after SCI in terms of providing trophic support, replacing lost cells, and regenerating functional neuronal architecture.…”

Section: Introductionmentioning

confidence: 99%

SDF-1 overexpression by mesenchymal stem cells enhances GAP-43-positive axonal growth following spinal cord injury

Stewart

Matyas

Welchko

et al. 2017

RNN

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Abstract.Purpose: Utilizing genetic overexpression of trophic molecules in cell populations has been a promising strategy to develop cell replacement therapies for spinal cord injury (SCI). Over-expressing the chemokine, stromal derived factor-1 (SDF-1␣), which has chemotactic effects on many cells of the nervous system, offers a promising strategy to promote axonal regrowth following SCI. The purpose of this study was to explore the effects of human SDF-1␣, when overexpressed by mesenchymal stem cells (MSCs), on axonal growth and motor behavior in a contusive rat model of SCI. Methods: Using a transwell migration assay, the paracrine effects of MSCs, which were engineered to secrete human SDF-1␣ (SDF-1-MSCs), were assessed on cultured neural stem cells (NSCs). For in vivo analyses, the SDF-1-MSCs, unaltered MSCs, or Hanks Buffered Saline Solution (vehicle) were injected into the lesion epicenter of rats at 9-days post-SCI. Behavior was analyzed for 7-weeks post-injury, using the Basso, Beattie, and Bresnahan (BBB) scale of locomotor functions. Immunohistochemistry was performed to evaluate major histopathological outcomes, including gliosis, inflammation, white matter sparing, and cavitation. New axonal outgrowth was characterized using immunohistochemistry against the neuron specific growth-associated protein-43 (GAP-43). Results:The results of these experiments demonstrate that the overexpression of SDF-1␣ by MSCs can enhance the migration of NSCs in vitro. Although only modest functional improvements were observed following transplantation of SDF-1-MSCs, a significant reduction in cavitation surrounding the lesion, and an increased density of GAP-43-positive axons inside the SCI lesion/graft site were found. Conclusion:The results from these experiments support the potential role for utilizing SDF-1␣ as a treatment for enhancing growth and regeneration of axons after traumatic SCI. Research HighlightsMSCs were engineered to overexpress SDF-1␣. SDF-1␣ expression by MSCs enhances the migration of NSCs in vitro. SDF-1␣ expression by MSCs enhanced GAP-43 fibers within the lesion center.

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“…Zendedel et al first corroborated that SDF‐1 improved functional recovery in a rat contusion model 77. SDF‐1 promoted transmigration of monocytes79 and macrophages80 into the injured cord, boosted astroglia and microglia responses,77 reduced the levels of IL‐18, IL‐1β, TNF‐α, and NLRP3,78 and thus regulated inflammation.…”

Section: Roles Of Inflammatory Cytokines In Sci Repairmentioning

confidence: 94%

“…SDF‐1 promoted transmigration of monocytes79 and macrophages80 into the injured cord, boosted astroglia and microglia responses,77 reduced the levels of IL‐18, IL‐1β, TNF‐α, and NLRP3,78 and thus regulated inflammation. SDF‐1 also decreased apoptosis and enhanced angiogenesis, chemotaxis and proliferation77 of cells, including NSCs,81, 82 subsequently enhancing axonal sprouting 83, 84…”

Section: Roles Of Inflammatory Cytokines In Sci Repairmentioning

confidence: 99%

Regulation of Inflammatory Cytokines for Spinal Cord Injury Repair Through Local Delivery of Therapeutic Agents

et al. 2018

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The balance of inflammation is critical to the repair of spinal cord injury (SCI), which is one of the most devastating traumas in human beings. Inflammatory cytokines, the direct mediators of local inflammation, have differential influences on the repair of the injured spinal cord. Some inflammatory cytokines are demonstrated beneficial to spinal cord repair in SCI models, while some detrimental. Various animal researches have revealed that local delivery of therapeutic agents efficiently regulates inflammatory cytokines and promotes repair from SCI. Quite a few clinical studies have also shown the promotion of repair from SCI through regulation of inflammatory cytokines. However, local delivery of a single agent affects only a part of the inflammatory cytokines that need to be regulated. Meanwhile, different individuals have differential profiles of inflammatory cytokines. Therefore, future studies may aim to develop personalized strategies of locally delivered therapeutic agent cocktails for effective and precise regulation of inflammation, and substantial functional recovery from SCI.

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Stromal cell-derived factor-1 alpha (SDF-1α) improves neural recovery after spinal cord contusion in rats

Cited by 34 publications

References 62 publications

Activation and Regulation of NLRP3 Inflammasome by Intrathecal Application of SDF-1a in a Spinal Cord Injury Model

Activation and Regulation of NLRP3 Inflammasome by Intrathecal Application of SDF-1a in a Spinal Cord Injury Model

SDF-1 overexpression by mesenchymal stem cells enhances GAP-43-positive axonal growth following spinal cord injury

Regulation of Inflammatory Cytokines for Spinal Cord Injury Repair Through Local Delivery of Therapeutic Agents

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