Background: Granulocyte-colony stimulating factor (G-CSF) has protective effects on
many neurological diseases. The effects of G-CSF on vascular endothelium and White Matter
(WM) injury in Cerebral Small Vessel Disease (CSVD) were explored in this study via a model of
spontaneously hypertensive rat (SHR) in order to elucidate the mechanism of G-CSF in Vascular
Cognitive Impairment (VCI).
Methods: 24-week-old male SHRs were randomly divided into the treatment group and model
group, with the same age Wistar rats as the control group. The novel object recognition test
(NORT) and Morris water maze were conducted after 7 days of G-CSF(50ug/kg) or normal saline
treatment to examine their non-spatial and spatial cognitive functions. After that, a transmission
electron microscope (TEM) and FLB staining were used to observe the vascular endothelial cell
and WM damage. Furthermore, the expression of VEGF, MMP-9, Caspase-3, TUNEL and BrdULaminin
in the cortical area was detected by immunostaining methods.
Results: 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 the cerebral
vascular endothelial cells and perivascular structure in SHR. The WM damage, 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 the spatial cognitive function.
Conclusion: Therefore, our findings indicated that G-CSF might facilitate the improvement of
non-spatial cognitive function in CSVD by repairing endothelial cells and alleviating WM damage.