Title:Granulocyte Colony-Stimulating Factor Attenuates Blood-Brain Barrier Damage and Improves Cognitive Function in Spontaneously Hypertensive Rats
Volume: 16
Issue: 7
Author(s): Xin Wei, Yan Xu*, Yanling Jin, Hongliang Feng, Yunyue Xiao and Shouquan Dong
Affiliation:
- Department of Neurology, Zhongnan Hospital of Wuhan University, No. 169 East Lake Road Wuchang District, Wuhan, 430071, Hubei,China
Keywords:
Astrogliosis, blood-brain barrier damage, cerebral small vessel disease, cognitive impairment, granulocyte-colony
stimulating factor, IgG, spontaneously hypertensive rats.
Abstract: Background: Cerebral small vessel diseases (CSVDs) always coincide with endothelial dysfunction
and blood-brain barrier (BBB) damage. However, the detailed mechanisms of CSVD are still
unclear and the therapeutic efficacy is not so satisfaction. Granulocyte-colony stimulating factor
(G-CSF) can play a neuroprotective role in many neurological diseases. We investigated whether
G-CSF exerted positive effects on BBB protection and cognitive function improvement in spontaneously
hypertensive rats (SHRs), a rat model displaying the early histopathological changes of CSVD.
Method: Twenty-four-week-old SHRs received daily administrations of either G-CSF (50µg/kg) or
normal saline (NS) for 7 days. The novel object recognition test (NORT) was then conducted after
treatment. After behavioral test, we examined IgG fluorescence staining to indicate BBB leakage.
G-CSF receptor (G-CSFR), aquaporin-4 (AQP4) and glial fibrillary acidic protein (GFAP) expression
were determined by immunofluorescence. The surface structure of endothelial cells was examined by
scanning electron microscopy (SEM).
Results: G-CSF significantly attenuated IgG leakage and improved non-spatial memory in SHRs.
G-CSFR was expressed at higher levels in both G-CSF-SHRs and NS-SHRs. The surface structural
changed on the endothelial cells and expression of AQP-4 and GFAP decreased after G-CSF treatment.
However, no significant differences in Claudin-5 expression were observed.
Conclusion: These findings demonstrated that the administration of exogenous G-CSF can improve
cognitive function in a model of CSVD, possibly due to the recovery of endothelial and BBB function.
