Advertisement
ADVANCED SEARCH

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: cmaj.051322v1 174/7/927    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shyu, W.-C. Articles by Li, H. Search for Related Content PubMed PubMed Citation Articles by Shyu, W.-C. Articles by Li, H. Related Collections Stroke Related Article

Granulocyte colony-stimulating factor for acute ischemic stroke: a randomized controlled trial

From the Neuro-Medical Scientific Center, Buddhist Tzu-Chi General Hospital (Shyu, Lin, Lee, Liu), Tzu-Chi University, Hualien, and the Institute of Molecular Biology, Academia Sinica (Li), Taipei, Taiwan

Correspondence to: Dr. Hung Li, Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan; hungli{at}ccvax.sinica.edu.tw, and Dr. Woei-Cherng Shyu, Neuro-Medical Scientific Center, Tzu-Chi Buddhist General Hospital, Tzu-Chi University, Hualien, Taiwan

Background: Because granulocyte colony-stimulating factor (G-CSF) has anti-inflammatory and neuroprotective properties and is known to mobilize stem cells, it may be useful in the treatment of acute ischemic stroke. We sought to examine the feasibility, safety and efficacy of using G-CSF to treat acute stroke.

Methods: We conducted a randomized, blinded controlled trial involving 10 patients with acute cerebral infarction (middle cerebral artery territory as documented by the admission MRI) who presented within 7 days of onset and whose scores on the National Institutes of Health Stroke Scale (NIHSS) were between 9 and 20. Patients were assigned to either G-CSF therapy or usual care. The G-CSF group (n = 7) received subcutaneous G-CSF injections (15 µg/kg per day) for 5 days. The primary outcome was percentage changes between baseline and 12-month follow-up in mean group scores on 4 clinical scales: the NIHSS, European Stroke Scale (ESS), ESS Motor Subscale (EMS) and Barthel Index (BI). We also assessed neurologic functioning using PET to measure cerebral uptake of fluorodeoxyglucose in the cortical areas surrounding the ischemic core.

Results: All of the patients completed the 5-day course of treatment, and none were lost to follow-up. No severe adverse effects were seen in patients receiving G-CSF. There was greater improvement in neurologic functioning between baseline and 12-month follow-up in the G-CSF group than in the control group (NIHSS: 59% change in the mean G-CSF group score v. 36% in the mean control group score, ESS: 33% v. 20%, EMS: 106% v. 58%, BI: 120% v. 60%). Although at 12 months there was no difference between the 2 groups in cerebral uptake of fluorodeoxyglucose in the ischemic core, uptake in the area surrounding the core was significantly improved in the G-CSF group compared with the control group. There was positive correlation between metabolic activity and EMS score following simple linear correlation analysis.

Interpretation: Our preliminary evidence suggests that using G-CSF as therapy for acute stroke is safe and feasible and leads to improved neurologic outcomes.

This article has been cited by other articles:

				M. Britschgi and T. Wyss-Coray Blood Protein Signature for the Early Diagnosis of Alzheimer Disease Arch Neurol, February 1, 2009; 66(2): 161 - 165. [Abstract] [Full Text] [PDF]

				A. Oishi, A. Otani, M. Sasahara, H. Kojima, H. Nakamura, Y. Yodoi, and N. Yoshimura Granulocyte Colony-Stimulating Factor Protects Retinal Photoreceptor Cells against Light-Induced Damage Invest. Ophthalmol. Vis. Sci., December 1, 2008; 49(12): 5629 - 5635. [Abstract] [Full Text] [PDF]

				Z. E. Toth, R. R. Leker, T. Shahar, S. Pastorino, I. Szalayova, B. Asemenew, S. Key, A. Parmelee, B. Mayer, K. Nemeth, et al. The combination of granulocyte colony-stimulating factor and stem cell factor significantly increases the number of bone marrow-derived endothelial cells in brains of mice following cerebral ischemia Blood, June 15, 2008; 111(12): 5544 - 5552. [Abstract] [Full Text] [PDF]

				J. Minnerup, J. Heidrich, J. Wellmann, A. Rogalewski, A. Schneider, and W.-R. Schabitz Meta-Analysis of the Efficacy of Granulocyte-Colony Stimulating Factor in Animal Models of Focal Cerebral Ischemia Stroke, June 1, 2008; 39(6): 1855 - 1861. [Abstract] [Full Text] [PDF]

				H.-K. Yip, L.-T. Chang, W.-N. Chang, C.-H. Lu, C.-W. Liou, M.-Y. Lan, J. S. Liu, A. A. Youssef, and H.-W. Chang Level and Value of Circulating Endothelial Progenitor Cells in Patients After Acute Ischemic Stroke Stroke, January 1, 2008; 39(1): 69 - 74. [Abstract] [Full Text] [PDF]

				N. Sprigg, P. M. Bath, L. Zhao, M. R. Willmot, L. J. Gray, M. F. Walker, M. S. Dennis, and N. Russell Granulocyte-Colony-Stimulating Factor Mobilizes Bone Marrow Stem Cells in Patients With Subacute Ischemic Stroke: The Stem Cell Trial of Recovery EnhanceMent After Stroke (STEMS) Pilot Randomized, Controlled Trial (ISRCTN 16784092) Stroke, December 1, 2006; 37(12): 2979 - 2983. [Abstract] [Full Text] [PDF]

				K. Kaptan, C. Beyan, and A. Ifran Granulocyte colony-stimulating factor. Can. Med. Assoc. J., October 24, 2006; 175(9): 1095 - 1095. [Full Text] [PDF]

				C. V. Borlongan and D. C. Hess Granulocyte colony-stimulating factor. Can. Med. Assoc. J., October 24, 2006; 175(9): 1096 - 1096. [Full Text] [PDF]

				J. P. Harriss Granulocyte colony-stimulating factor. Can. Med. Assoc. J., October 24, 2006; 175(9): 1095 - 1095. [Full Text] [PDF]

				W.-C. Shyu, S.-Z. Lin, and H. Li Granulocyte colony-stimulating factor. Can. Med. Assoc. J., October 24, 2006; 175(9): 1095 - 1096. [Full Text] [PDF]

				W.-R. Schabitz and A. Schneider Developing Granulocyte-Colony Stimulating Factor for the Treatment of Stroke: Current Status of Clinical Trials Stroke, July 1, 2006; 37(7): 1654 - 1654. [Full Text] [PDF]

				I. Solaroglu, J. Cahill, V. Jadhav, and J. H. Zhang Response to Letter by Schabitz et al Stroke, July 1, 2006; 37(7): 1655 - 1655. [Full Text] [PDF]

				C. V. Borlongan and D. C. Hess New hope for stroke patients: mobilization of endogenous stem cells Can. Med. Assoc. J., March 28, 2006; 174(7): 954 - 955. [Full Text] [PDF]

HOME	CURRENT ISSUE	PAST ISSUES	COLLECTIONS	HELP	SEARCH
Copyright 1995-2006, Canadian Medical Association. All rights reserved. ISSN 1488-2329 (e) 0820-3946 (p) All editorial matter in CMAJ represents the opinions of the authors and not necessarily those of the Canadian Medical Association.