Granulocyte-Colony Stimulating Factor Increases Cerebral Blood Flow via a NO Surge Mediated by Akt/eNOS Pathway to Reduce Ischemic Injury. (4th June 2015)

• Record Type: Journal Article
• Authors: Liew, Hock-Kean; Kuo, Jon-Son; Wang, Jia-Yi; Pang, Cheng-Yoong
• Other Names: Starke Robert M. Academic Editor.
• Is Part Of: TheScientificWorldjournal. Volume 2015(2015)
• Publication Date: 2015-06-04
• Subjects: Science -- Periodicals; Technology -- Periodicals; Medicine -- Periodicals; 505
• DOI: 10.1155/2015/657932
• Languages: English
• ISSNs: 2356-6140

Abstract

Abstract : 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- N G -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.