Granulocyte colony-stimulating factor (G-CSF) mobilizes bone marrow-derived cells into injured spinal cord and promotes functional recovery after compression-induced spinal cord injury in mice

Koda, Masao; Nishio, Yutaka; Kamada, Takahito; Someya, Yuichi; Okawa, Akihiko; Mori, Chisato; Yoshinaga, Katsunori; Okada, Seiji; Moriya, Hideshige; Yamazaki, Masashi

doi:10.1016/j.brainres.2007.02.058

Cited by 110 publications

(58 citation statements)

References 33 publications

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“…Thus, G-CSF may be an appropriate substitute for GM-CSF in treating SCI; it has similar effects on CNS injuries, but unlike many other materials, it has already been approved as a safe drug with neuroprotective effects via any injection route. 17 With regards to glial scar formation, G-CSF suppressed the expression of CSPGs and GFAP. Because G-CSF suppresses GFAP expression after SCI, it might also suppress astrocyte activation within glial scars after SCI, resulting in the down-regulation of CSPG expression and other inhibitory molecules for axonal regeneration.…”

Section: Discussionmentioning

confidence: 99%

“…G-CSF also promotes the restoration of damaged spinal cord tissue by mobilizing bone marrow cells into the spinal cord, 17 enhances the availability of circulating hematopoietic stem cells in neuronal lesion sites and enhances their ability for neurogenesis and angiogenesis, 20 and inhibits apoptosis of neural cells by regulating the expression of apoptosis-related proteins. 10 Despite the beneficial effects of G-CSF on functional recovery after SCI, the influence of G-CSF on glial scar formation is not yet known.…”

Section: 20mentioning

confidence: 99%

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Effects of granulocyte colony–stimulating factor and granulocyte-macrophage colony–stimulating factor on glial scar formation after spinal cord injury in rats

Chung

Kim²,

Yoon³

et al. 2014

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Object This study investigated the effects of granulocyte colony–stimulating factor (G-CSF) on glial scar formation after spinal cord injury (SCI) in rats and compared the therapeutic effects between G-CSF and granulocytemacrophage colony–stimulating factor (GM-CSF) to evaluate G-CSF as a potential substitute for GM-CSF in clinical application. Methods Rats were randomly assigned to 1 of 4 groups: a sham-operated group (Group 1), an SCI group without treatment (Group 2), an SCI group treated with G-CSF (Group 3), and an SCI group treated with GM-CSF (Group 4). G-CSF and GM-CSF were administered via intraperitoneal injection immediately after SCI. The effects of G-CSF and GM-CSF on functional recovery, glial scar formation, and axonal regeneration were evaluated and compared. Results The rats in Groups 3 and 4 showed better functional recovery and more decreased cavity sizes than those in Group 2 (p < 0.05). Both G-CSF and GM-CSF suppressed intensive expression of glial fibrillary acidic protein around the cavity at 4 weeks and reduced the expression of chondroitin sulfate proteoglycans (p < 0.05). Also, early administration of G-CSF and GM-CSF protected axon fibers from destructive injury and facilitated axonal regeneration. There were no significant differences in comparisons of functional recovery, glial scar formation, and axonal regeneration between G-CSF and GM-CSF. Conclusions G-CSF suppressed glial scar formation after SCI in rats, possibly by restricting the expression of glial fibrillary acidic protein and chondroitin sulfate proteoglycans, which might facilitate functional recovery from SCI. GM-CSF and G-CSF had similar effects on glial scar formation and functional recovery after SCI, suggesting that G-CSF can potentially be substituted for GM-CSF in the treatment of SCI.

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Section: Discussionmentioning

confidence: 99%

Section: 20mentioning

confidence: 99%

Effects of granulocyte colony–stimulating factor and granulocyte-macrophage colony–stimulating factor on glial scar formation after spinal cord injury in rats

Chung

Kim²,

Yoon³

et al. 2014

SPI

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“…Later, Yamazaki et al first applied G‐CSF in a mouse SCI model and reported hindlimb functional recovery 38, 101. G‐CSF was discovered to attenuate neuronal death38 and enhance connectivity 39.…”

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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“…We previously demonstrated that G-CSF promoted the restoration of damaged spinal cord tissue and the recovery of neural function in experimental spinal cord injury in both mice and rats [8,14]. In addition, we showed that G-CSF promoted the migration of bone marrow-derived cells into the damaged spinal cord, suppressed apoptosis of neuronal cells and oligodendrocytes, protected myelin, decreased inflammation, and promoted angiogenesis [8,14]. Based on these results, we have suggested that G-CSF is a candidate for neuroprotective therapy for worsening symptoms of compression myelopathy.…”

Section: Introductionmentioning

confidence: 99%

“…Several recent reports have indicated that G-CSF also has nonhematopoietic functions and can potentially be used for the treatment of neuronal injury, including stroke and neurodegenerative diseases [4,7,9,18,20]. We previously demonstrated that G-CSF promoted the restoration of damaged spinal cord tissue and the recovery of neural function in experimental spinal cord injury in both mice and rats [8,14]. In addition, we showed that G-CSF promoted the migration of bone marrow-derived cells into the damaged spinal cord, suppressed apoptosis of neuronal cells and oligodendrocytes, protected myelin, decreased inflammation, and promoted angiogenesis [8,14].…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective therapy using granulocyte colony-stimulating factor for patients with worsening symptoms of compression myelopathy, part 1: a phase I and IIa clinical trial

et al. 2011

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Objective Based on the neuroprotective effects of granulocyte colony-stimulating factor (G-CSF) on experimental spinal cord injury, we initiated a clinical trial that evaluated the safety and efficacy of neuroprotective therapy using G-CSF for patients with worsening symptoms of compression myelopathy. Methods We obtained informed consent from 15 patients, in whom the Japanese Orthopaedic Association (JOA) score for cervical myelopathy decreased two points or more during a recent 1-month period. G-CSF (5 or 10 lg/kg/day) was intravenously administered for five consecutive days. We evaluated motor and sensory functions of the patients and the presence of adverse events related to G-CSF therapy.

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Granulocyte colony-stimulating factor (G-CSF) mobilizes bone marrow-derived cells into injured spinal cord and promotes functional recovery after compression-induced spinal cord injury in mice

Cited by 110 publications

References 33 publications

Effects of granulocyte colony–stimulating factor and granulocyte-macrophage colony–stimulating factor on glial scar formation after spinal cord injury in rats

Effects of granulocyte colony–stimulating factor and granulocyte-macrophage colony–stimulating factor on glial scar formation after spinal cord injury in rats

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

Neuroprotective therapy using granulocyte colony-stimulating factor for patients with worsening symptoms of compression myelopathy, part 1: a phase I and IIa clinical trial

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