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The Scientific World Journal
Volume 2015, Article ID 657932, 8 pages
Research Article

Granulocyte-Colony Stimulating Factor Increases Cerebral Blood Flow via a NO Surge Mediated by Akt/eNOS Pathway to Reduce Ischemic Injury

1Department of Medical Research, Buddhist Tzu Chi General Hospital, No. 707, Section 3, Zhongyang Road, Hualien City 970, Taiwan
2Institute of Pharmacology and Toxicology, Tzu Chi University, No. 701, Section 3, Zhongyang Road, Hualien City 970, Taiwan
3Graduate Institute of Medical Sciences, Taipei Medical University, No. 250, Wu-Hsing Street, Taipei 110, Taiwan
4Institute of Medical Sciences, Tzu Chi University, No. 701, Section 3, Zhongyang Road, Hualien City 970, Taiwan

Received 20 June 2014; Revised 6 November 2014; Accepted 7 November 2014

Academic Editor: Robert M. Starke

Copyright © 2015 Hock-Kean Liew et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Granulocyte-colony stimulating factor (G-CSF) protects brain from ischemic/reperfusion (I/R) injury, and inhibition of nitric oxide (NO) synthases partially reduces G-CSF protection. We thus further investigated the effects of G-CSF on ischemia-induced NO production and its consequence on regional cerebral blood flow (rCBF) and neurological deficit. Endothelin-1 (ET-1) microinfused above middle cerebral artery caused a rapid reduction of rCBF (ischemia) which lasted for 30 minutes and was followed by a gradual recovery of blood flow (reperfusion) within the striatal region. Regional NO concentration increased rapidly (NO surge) during ischemia and recovered soon to the baseline. G-CSF increased rCBF resulting in shorter ischemic duration and an earlier onset of reperfusion. The enhancement of the ischemia-induced NO by G-CSF accompanied by elevation of phospho-Akt and phospho-eNOS was noted, suggesting an activation of Akt/eNOS. I/R-induced infarct volume and neurological deficits were also reduced by G-CSF treatment. Inhibition of NO synthesis by L-NG-Nitroarginine Methyl Ester (L-NAME) significantly reduced the effects of G-CSF on rCBF, NO surge, infarct volume, and neurological deficits. We conclude that G-CSF increases rCBF through a NO surge mediated by Akt/eNOS, which partially contributes to the beneficial effect of G-CSF on brain I/R injury.