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


METHODS
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.


CONCLUSIONS
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.
Department of Neurology, Zhongnan Hospital of Wuhan University, Hubei, 430071. China.
Xin
X
Wei
Department of Neurology, Zhongnan Hospital of Wuhan University, No. 169 East Lake Road Wuchang District, Wuhan, 430071, Hubei. China.
Yan
Y
Xu
Department of Neurology, Zhongnan Hospital of Wuhan University, Hubei, 430071. China.
Yanling
Y
Jin
Department of Neurology, Zhongnan Hospital of Wuhan University, Hubei, 430071. China.
Hongliang
H
Feng
Department of Neurology, Zhongnan Hospital of Wuhan University, Hubei, 430071. China.
Yunyue
Y
Xiao
Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Hubei, 430071. China.
Shouquan
S
Dong
D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D059345:Cerebral Small Vessel Diseases / Q000188:drug therapy*; D062507:Claudin-5 / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D042783:Endothelial Cells / Q000648:ultrastructure; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use*; D007074:Immunoglobulin G / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D021641:Recognition, Psychology / Q000187:drug effects
D051401:Aquaporin 4; D062507:Claudin-5; D005904:Glial Fibrillary Acidic Protein; D007074:Immunoglobulin G; D018696:Neuroprotective Agents; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor
Astrogliosis; IgG; blood-brain barrier damage; cerebral small vessel disease; cognitive impairment; granulocyte-colony
stimulating factor; spontaneously hypertensive rats