Role of granulocyte colony-stimulating factor in protection of cerebral vascular endothelium, white matter, and cognition.

Granulocyte-colony stimulating factor (G-CSF) has protective effects on many neurological diseases. We explored the effects of G-CSF on vascular endothelium and white matter (WM) injury in cerebral small vessel disease(CSVD) via the model of spontaneously hypertensive rat(SHR) so as to elucidate the mechanism of G-CSF on vascular cognitive impairment(VCI).24 week male SHRs were randomly divided into treatment group and model group , with the same age wistar as the control group. The novel object recognition test (NORT)and Morris water maze were conducted after 7 days' G-CSF(50ug/kg) or normal saline treatment to examine their non-spatial and spatial cognitive function. After that, we use transmission electron microscope(TEM) and FLB staining to observe the vascular endothelial cell and WM damage. Furthermore, the expression of VEGF, MMP-9, Caspase-3 ,TUNEL and BrdU-Laminin in cortical area were detected by immunostaining methods.Our results showed that G-CSF promoted the expression of VEGF and BrdU+-Laminin+ endothelial cells,but down regulated the level of MMP-9, thus significantly repaired cerebral vascular endothelial cells and perivascular structure in SHR. The WM damage and the expression of caspase-3 and the apoptosis rate decreased after G-CSF treatment. Ultimately, G-CSF improved the non-spatial cognitive function in SHR rather than spatial cognitive function.Therefore,our findings indicated that G-CSF may facilitate non-spatial cognitive function improvement in CSVD by repairing endothelial cells and alleviating WM damage.