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Neuroprotective Therapy Using Granulocyte Colony-Stimulating Factor for Acute Spinal Cord Injury: A Multicenter Prospective Controlled Clinical Trial

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Neuroprotection and Regeneration of the Spinal Cord

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Abstract

We conducted a multicenter prospective controlled clinical trial to assess the feasibility of neuroprotective therapy using granulocyte colony-stimulating factor (G-CSF) for patients with acute spinal cord injury (SCI). The trial ran from August 2009 to March 2011 and included 45 SCI patients treated within 48 h of onset. Informed consent was obtained from all patients. After providing consent, patients were divided into two groups. In the G-CSF group (19 patients), G-CSF (10 μg/kg/day) was intravenously administered for five consecutive days, and in the control group (26 patients), patients were similarly treated except for the G-CSF administration. We evaluated motor functions using the American Spinal Cord Injury Association (ASIA) score 3 months after onset. The increase in ASIA motor score was significantly higher in the G-CSF group (26.1 ± 18.9) than in the control group (12.2 ± 14.7) (P < 0.01). In cases of incomplete paralysis (18 patients in the G-CSF group and 19 patients in the control group), the increase in motor score was also significantly higher (P < 0.05) in the G-CSF group (27.1 ± 18.9) than in the control group (15.1 ± 15.9). The present results suggest the possibility that G-CSF administration has beneficial effects on neurological recovery in patients with acute SCI. We believe that neuroprotection using G-CSF is an effective therapeutic strategy for acute SCI treatment.

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References

  1. Pannu R, Barbosa E, Singh AK, Singh I (2005) Attenuation of acute inflammatory response by atorvastatin after spinal cord injury in rats. J Neurosci Res 79(3):340–350

    Article  CAS  PubMed  Google Scholar 

  2. Bracken MB, Shepard MJ, Collins WF, Holford TR, Young W, Baskin DS et al (1990) A randomized controlled trial of methylprednisolone or naloxone in the treatment of acute spinal cord injury: results of the second national acute spinal cord injury study. N Engl J Med 322(20):1405–1411

    Article  CAS  PubMed  Google Scholar 

  3. Bracken MB, Shepard MF, Holford TR, Leo Summers L, Aldrich EF, Fazl M et al (1997) Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury: results of the third national acute spinal injury randomized controlled trial. JAMA 277(20):1597–1604

    Article  CAS  PubMed  Google Scholar 

  4. Hurlbert RJ (2000) Methylprednisolone for acute spinal cord injury: an inappropriate standard of care. J Neurosurg 93(1 Suppl):1–7

    CAS  PubMed  Google Scholar 

  5. Ito Y, Sugimoto Y, Tomioka M, Kai N, Tanaka M (2009) Does high dose methylprednisolone sodium succinate really improve neurological status in patient with acute cervical cord injury?: a prospective study about neurological recovery and early complications. Spine 34(20):2121–2124

    Article  PubMed  Google Scholar 

  6. Pointillart V, Petitjean ME, Wiart L, Vital JM, Lassie P, Thicoipe M et al (2000) Pharmacological therapy of spinal cord injury during the acute phase. Spinal Cord 38(2):71–76

    Article  CAS  PubMed  Google Scholar 

  7. Polland ME, Apple DF (2003) Factors associated with improved neurologic outcomes in patients with incomplete tetraplegia. Spine 28(1):33–39

    Article  Google Scholar 

  8. Matsumoto T, Tamaki T, Kawakami M, Yoshida M, Ando M, Yamada H (2001) Early complications of high-dose methyl-prednisolone sodium succinate treatment in the follow-up of acute cervical spinal cord injury. Spine 26(4):426–430

    Article  CAS  PubMed  Google Scholar 

  9. Nicola NA, Metcalf D, Matsumoto M, Johnson GR (1983) Purification of a factor inducing differentiation in murine myelomonocytic leukemia cells. Identification as granulocyte colony-stimulating factor J Biol Chem 258(14):9017–9023

    CAS  Google Scholar 

  10. Roberts AW (2005) G-CSF: a key regulator of neutrophil production, but that's not all! Growth Factors 23(1):33–41

    Article  CAS  PubMed  Google Scholar 

  11. Gibson CL, Jones NC, Prior MJ, Bath PM, Murphy SP (2005) G-CSF suppresses edema formation and reduces interleukin-1β expression after cerebral ischemia in mice. J Neuropathol Exp Neurol 64(9):763–769

    Article  CAS  PubMed  Google Scholar 

  12. Kawada H, Takizawa S, Takanashi T, Morita Y, Fujita J, Fukuda K et al (2006) Administration of hematopoietic cytokines in the subacute phase after cerebral infarction is effective for functional recovery facilitating proliferation of intrinsic neural stem/progenitor cells and transition of bone marrow-derived neuronal cells. Circulation 113(5):701–710

    Article  CAS  PubMed  Google Scholar 

  13. Komine-Kobayashi M, Zhang N, Liu M, Tanaka R, Hara H, Osaka A et al (2006) Neuroprotective effect of recombinant human granulocyte colony-stimulating factor in transient focal ischemia of mice. J Cereb Blood Flow Metab 26(3):402–413

    Article  CAS  PubMed  Google Scholar 

  14. Schäbitz WR, Kollmar R, Schwaninger M, Juettler E, Bardutzky J, Schölzke MN et al (2003) Neuroprotective effect of granulocyte colony-stimulating factor after focal cerebral ischemia. Stroke 34(3):745–751

    Article  PubMed  Google Scholar 

  15. Schneider A, Kuhn HG, Schäbitz WR (2005) A role for G-CSF (granulocyte-colony stimulating factor) in the central nervous system. Cell Cycle 4(12):1753–1757

    Article  CAS  PubMed  Google Scholar 

  16. Koda M, Nishio Y, Kamada T, Someya Y, Okawa A, Mori C et al (2007) 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. Brain Res 1149:223–231

    Article  CAS  PubMed  Google Scholar 

  17. Nishio Y, Koda M, Kamada T, Someya Y, Kadota R, Mannoji C et al (2007) Granulocyte colony-stimulating factor attenuates neuronal death and promotes functional recovery after spinal cord injury in mice. J Neuropathol Exp Neurol 66(8):724–731

    Article  CAS  PubMed  Google Scholar 

  18. Kawabe J, Koda M, Hashimoto M, Fujiyoshi T, Furuya T, Endo T et al (2011) Neuroprotective effects of granulocyte colony-stimulating factor and relationship to promotion of angiogenesis after spinal cord injury in rats: laboratory investigation. J Neurosurg Spine 15(4):414–421

    Article  PubMed  Google Scholar 

  19. Kadota R, Koda M, Kawabe J, Hashimoto M, Nishio Y, Mannoji C et al (2012) Granulocyte colony-stimulating factor (G-CSF) protects oligodendrocyte and promotes hindlimb functional recovery after spinal cord injury in rats. PLoS One 7(11):e50391

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Maynard FM Jr, Bracken MB, Creasey G, Ditunno JF Jr, Donovan WH, Ducker TB et al (1997) International standards for neurological and functional classification of spinal cord injury. Am Spinal Inj Assoc Spinal Cord 35(5):266–274

    Google Scholar 

  21. Iwasaki H, Kawamoto A, Ishikawa M, Oyamada A, Nakamori S, Nishimura H et al (2006) Dose-dependent contribution of CD34-positive cell transplantation to concurrent vasculogenesis and cardiomyogenesis for functional regenerative recovery after myocardial infarction. Circulation 113(10):1311–1325

    Article  CAS  PubMed  Google Scholar 

  22. Engelmann MG, Theiss HD, Hennig-Theiss C, Huber A, Wintersperger BJ, Werle-Ruedinger AE et al (2006) Autologous bone marrow stem cell mobilization induced by granulocyte colony-stimulating factor after subacute ST-segment elevation myocardial infarction undergoing late revascularization: final results from the G-CSF-STMI (Granulocyte Colony-Stimulating Factor ST-Segment Elevation Myocardial Infarction) trial. J Am Coll Cardiol 48(8):1712–1721

    Article  CAS  PubMed  Google Scholar 

  23. Ince H, Petzsch M, Kleine HD, Eckard H, Rehders T, Burska D et al (2005) Prevention of left ventricular remodeling with granulocyte colony-stimulating factor after acute myocardial infarction: final 1-year results of the front-integrated revascularization and stem cell liberation in evolving acute myocardial infarction by granulocyte colony-stimulating factor (FIRSTLINE-AMI) trial. Circulation 112(9 suppl):173–180

    Google Scholar 

  24. Ripa RS, Jorgensen E, Wang Y, Thune JJ, Nilsson JC, Sondergaard L et al (2006) Stem cell mobilization induced by subcutaneous granulocyte colony-stimulating factor to improve cardiac regeneration after acute ST-elevation myocardial infarction: result of the double-blind, randomized, placebo-controlled stem cells in myocardial infarction (STEMMI) trial. Circulation 113(16):1983–1992

    Article  CAS  PubMed  Google Scholar 

  25. Takano H, Hasegawa H, Kuwabara Y, Nakayama T, Matsuno K, Miyazaki Y et al (2007) Feasibility and safety of granulocyte colony-stimulating factor treatment in patients with acute myocardial infarction. Int J Cardiol 122(1):41–47

    Article  PubMed  Google Scholar 

  26. Valgimigli M, Rigolin GM, Cittanti C, Malagutti P, Curello S, Percoco G et al (2005) Use of granulocyte-colony stimulating factor during acute myocardial infarction to enhance bone marrow stem cell mobilization in humans: clinical and angiographic safety profile. Eur Heart J 26(18):1838–1845

    Article  CAS  PubMed  Google Scholar 

  27. Zohlnhofer D, Ott I, Mehilli J, Schomig K, Michalk F, Ibrahim T et al (2006) REVIVAL-2 investigators: stem cell mobilization by granulocyte colony-stimulating factor in patients with acute myocardial infarction: a randomized controlled trial. JAMA 295(9):1003–1010

    Article  PubMed  Google Scholar 

  28. Shyu WC, Lin SZ, Lee CC, Liu DD, Li H (2006) Granulocyte colony-stimulating factor for acute ischemic stroke: a randomized controlled trial. CMAJ 174(7):927–933

    Article  PubMed Central  PubMed  Google Scholar 

  29. Nefussy B, Artamonov I, Deutsch V, Naparstek E, Nagler A, Drory VE (2010) Recombinant human granulocyte-colony stimulating factor administration for treating amyotrophic lateral sclerosis: A pilot study. Amyotroph Lateral Scler 11(1–2):187–193

    Article  CAS  PubMed  Google Scholar 

  30. Zhang Y, Wang L, Fu Y, Song H, Zhao H, Deng M et al (2009) Preliminary investigation of effect of granulocyte colony stimulating factor on amyotrophic lateral sclerosis. Amyotroph Lateral Scler 10(5–6):430–431

    Article  CAS  PubMed  Google Scholar 

  31. Takahashi H, Yamazaki M, Okawa A, Sakuma T, Kato K, Hashimoto M et al (2012) Neuroprotective therapy using granulocyte colony-stimulating factor for acute spinal cord injury: a phase I/IIa clinical trial. Eur Spine J 21(12):2580–2587

    Article  PubMed Central  PubMed  Google Scholar 

  32. Sakuma T, Yamazaki M, Okawa A, Takahashi H, Kato K, Hashimoto M et al (2012) Neuroprotective therapy using granulocyte-colony stimulating factor for patients with worsening symptoms of compression myelopathy, part 1: a phase I and IIa clinical trial. Eur Spine J 21(3):482–489

    Article  PubMed Central  PubMed  Google Scholar 

  33. Sakuma T, Yamazaki M, Okawa A, Takahashi H, Kato K, Hashimoto M et al (2012) Neuroprotective therapy using granulocyte-colony stimulating factor for patients with worsening symptoms of thoracic myelopathy, a multicenter prospective controlled trial. Spine 37(17):1475–1478

    Article  PubMed  Google Scholar 

  34. Anderlini P, Przepiorka D, Seong D, Miller P, Sundberg J, Lichtiger B et al (1996) Clinical toxicity and laboratory effects of granulocyte colony-stimulating factor (filgrastim) mobilization and blood stem cell apheresis from normal donors and analysis of charge for procedures. Transfusion 36(7):590–595

    Article  CAS  PubMed  Google Scholar 

  35. Becker PS, Wagle M, Matous S, Swanson RS, Pihan G, Lowry PA et al (1997) Spontaneous splenic rupture following administration of granulocyte colony-stimulating factor (G-CSF) occurrence in an allogeneic donor of peripheral blood stem cells. Biol Blood Marrow Transplant 3(1):45–49

    CAS  PubMed  Google Scholar 

  36. Murata M, Harada M, Kato S, Takahashi S, Ogawa H, Okamoto S et al (1999) Peripheral blood stem cell mobilization and apheresis: analysis of adverse events in 94 normal donors. Bone Marrow Transplant 24(10):1065–1071

    Article  CAS  PubMed  Google Scholar 

  37. Falzetti F, Aversa F, Minelli O, Tabilio A (1999) Spontaneous rupture of spleen during peripheral blood stem cell mobilization in a healthy donor. Lancet 353(9152):555

    CAS  PubMed  Google Scholar 

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Acknowledgment

 The authors thank Drs. Takayuki Fujiyoshi, Tsuyoshi Sakuma, Kei Kato, Mitsuhiro Hashimoto, Koichi Hayashi, Junko Kawabe, Chikato Mannoji, Tomohiro Miyashita, Ryo Kadota, Yukio Someya, Osamu Ikeda, Masayuki Hashimoto, Akihiko Okawa, and Kazuhisa Takahashi (Department of Orthopaedic Surgery, Chiba University Graduate School of Medicine), Drs. Kota Suda, Tomomichi Kajino, and Haruki Ueda (Spinal Cord Injury Center, Hokkaido Chuo Rosai Hospital), Dr. Yasuo Ito (Department of Orthopaedic Surgery, Kobe Red Cross Hospital), Dr. Takayoshi Ueta (Department of Orthopaedic Surgery, Japan LHWO Spinal Injuries Center), and Dr. Hideki Hanaoka (Department of Clinical Research, Chiba University Hospital) for their kind support in the present study. This work was supported by a Health Labor Science Research Grant of Japan.

Conflict of Interest  Authors (Masashi Yamazaki, Hiroshi Takahashi, Takeo Furuya, and Masao Koda) declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-City, Ibaraki, 305-8575, Japan

    Masashi Yamazaki

  2. Department of Orthopaedic Surgery, Chiba University Graduate School of Medicine, Chiba, Japan

    Hiroshi Takahashi, Takeo Furuya & Masao Koda

Authors
  1. Masashi Yamazaki
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  2. Hiroshi Takahashi
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  3. Takeo Furuya
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  4. Masao Koda
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Correspondence to Masashi Yamazaki .

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Editors and Affiliations

  1. Dept of Orthop & Rehabilit Med, University of Fukui Faculty of Medical Sciences, Yoshida-gun, Fukui, Japan

    Kenzo Uchida

  2. Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Tokyo, Japan

    Masaya Nakamura

  3. Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

    Hiroshi Ozawa

  4. Department of Orthopedic Surgery, Faculty of Medicine The University of Tokushima, Tokushima, Tokushima, Japan

    Shinsuke Katoh

  5. Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Tokyo, Japan

    Yoshiaki Toyama

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Yamazaki, M., Takahashi, H., Furuya, T., Koda, M. (2014). Neuroprotective Therapy Using Granulocyte Colony-Stimulating Factor for Acute Spinal Cord Injury: A Multicenter Prospective Controlled Clinical Trial. In: Uchida, K., Nakamura, M., Ozawa, H., Katoh, S., Toyama, Y. (eds) Neuroprotection and Regeneration of the Spinal Cord. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54502-6_27

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  • DOI: https://doi.org/10.1007/978-4-431-54502-6_27

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  • Publisher Name: Springer, Tokyo

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  • Online ISBN: 978-4-431-54502-6

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