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Granulocyte Colony-Stimulating Factor Attenuates Blood-Brain Barrier Damage and Improves Cognitive Function in Spontaneously Hypertensive Rats

[ Vol. 16 , Issue. 7 ]

Author(s):

Xin Wei, Yan Xu*, Yanling Jin, Hongliang Feng, Yunyue Xiao and Shouquan Dong   Pages 781 - 788 ( 8 )

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.

Keywords:

Astrogliosis, blood-brain barrier damage, cerebral small vessel disease, cognitive impairment, granulocyte-colony stimulating factor, IgG, spontaneously hypertensive rats.

Affiliation:

Department of Neurology, Zhongnan Hospital of Wuhan University, Hubei, 430071, Department of Neurology, Zhongnan Hospital of Wuhan University, No. 169 East Lake Road Wuchang District, Wuhan, 430071, Hubei, Department of Neurology, Zhongnan Hospital of Wuhan University, Hubei, 430071, Department of Neurology, Zhongnan Hospital of Wuhan University, Hubei, 430071, Department of Neurology, Zhongnan Hospital of Wuhan University, Hubei, 430071, Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Hubei, 430071

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