Granulocyte Colony-Stimulating Factor Attenuates Neuronal Death and Promotes Functional Recovery After Spinal Cord Injury in Mice

Nishio, Yutaka; Koda, Masao; Kamada, Takahito; Someya, Yuichi; Kadota, Ryo; Mannoji, Chikato; Miyashita, Tetsuya; Okada, Seiji; Okawa, Akihiko; Moriya, Hideshige; Yamazaki, Masashi

doi:10.1097/nen.0b013e3181257176

Cited by 109 publications

(83 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, G-CSF promoted neuronal survival, oligodendrocyte protection, and functional recovery in animal models of spinal cord injury (SCI) (47,76). In phase I/IIa clinical trials, the safety and feasibility of G-CSF as a neuroprotective therapy in patients with acute SCI were described, indicating the possibility for G-CSF to improve neurological and functional outcomes in patients with acute SCI (110).…”

Section: Therapeutic Uses Of G-csfmentioning

confidence: 99%

G-CSF as an Adjunctive Therapy with Umbilical Cord Blood Cell Transplantation for Traumatic Brain Injury

et al. 2015

View full text Add to dashboard Cite

Traumatic brain injury (TBI), a major contributor to deaths and permanent disability worldwide, has been recently described as a progressive cell death process rather than an acute event. TBI pathophysiology is complicated and can be distinguished by the initial primary injury and the subsequent secondary injury that ensues days after the trauma. Therapeutic opportunities for TBI remain very limited with patients subjected to surgery or rehabilitation therapy. The efficacy of stem cell-based interventions, as well as neuroprotective agents in other neurological disorders of which pathologies overlap with TBI, indicates their potential as alternative TBI treatments. Furthermore, their therapeutic limitations may be augmented when combination therapy is pursued instead of using a single agent. Indeed, we demonstrated remarkable combined efficacy of human umbilical cord blood (hUCB) cell therapy and granulocyte-colony-stimulating factor (G-CSF) treatment in TBI models, providing essential evidence for the translation of this approach to treat TBI. Further studies are warranted to determine the mechanisms underlying therapeutic benefits exerted by hUCB + G-CSF in order to enhance its safety and efficacy in the clinic.

show abstract

Section: Therapeutic Uses Of G-csfmentioning

confidence: 99%

G-CSF as an Adjunctive Therapy with Umbilical Cord Blood Cell Transplantation for Traumatic Brain Injury

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Cell counting included the area from either 300 to 800 μm rostral or 300 to 800 μm caudal to the lesion epicenter as previously described. 19 The examiners were blinded as to the treatment condition of the mice.…”

Section: Double Immunofluorescence Stainingmentioning

confidence: 99%

“…G-CSFR is present within the CNS 17 and increasing evidence has revealed that G-CSF may inhibit neuronal apoptosis associated with neural injury/disease and, in this way, promote neuroprotective effects. [18][19][20] In particular, G-CSF has been shown to exert beneficial effects via an anti-autophagic mechanism in cardiomyopathic hamster models. 21 Based upon these findings, the potential for G-CSF to function as a neuroprotectant in acute SCI attracted our attention.…”

mentioning

confidence: 99%

G-CSF promotes autophagy and reduces neural tissue damage after spinal cord injury in mice

Guo

Liu

Zhang

et al. 2015

Laboratory Investigation

View full text Add to dashboard Cite

Granulocyte colony-stimulating factor (G-CSF) was investigated for its capacity to induce autophagy and related neuroprotective mechanisms in an acute spinal cord injury model. To accomplish this goal, we established a mouse spinal cord hemisection model to test the effects of recombinant human G-CSF. The results showed that autophagy was activated after spinal cord injury and G-CSF appears to induce a more rapid activation of autophagy within injured spinal cords as compared with that of non-treated animals. Apoptosis as induced in mechanically injured neurons with G-CSF treatment was enhanced after inhibiting autophagy by 3-methyladenine (3-MA), which partially blocked the neuroprotective effect of autophagy as induced by G-CSF. In addition, G-CSF inhibited the activity of the NF-κB signal pathway in neurons after mechanical injury. We conclude that G-CSF promotes autophagy by inhibiting the NF-κB signal pathway and protects neuronal structure after spinal cord injury. We therefore suggest that G-CSF, which rapidly induces autophagy after spinal cord injury to inhibit neuronal apoptosis, may thus provide an effective auxiliary therapeutic intervention for spinal cord injury.

show abstract

“…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%

“…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%

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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Granulocyte Colony-Stimulating Factor Attenuates Neuronal Death and Promotes Functional Recovery After Spinal Cord Injury in Mice

Cited by 109 publications

References 26 publications

G-CSF as an Adjunctive Therapy with Umbilical Cord Blood Cell Transplantation for Traumatic Brain Injury

G-CSF as an Adjunctive Therapy with Umbilical Cord Blood Cell Transplantation for Traumatic Brain Injury

G-CSF promotes autophagy and reduces neural tissue damage after spinal cord injury in mice

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

Contact Info

Product

Resources

About