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

Abstract EN

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.