Granulocyte Colony-Stimulating Factor Attenuates Blood-Brain Barrier Damage and Improves Cognitive Function in
Xin Wei1, Yan Xu2, Yanling Jin1
1Department of Neurology, Zhongnan Hospital of Wuhan University, Hubei, 430071. China.
Insights
Granulocyte-colony stimulating factor (G-CSF) improved cognitive function and blood-brain barrier (BBB) integrity in a rat model of cerebral small vessel disease (CSVD). This suggests G-CSF may be a potential therapeutic agent for neurological conditions involving BBB damage.
Area of Science:
- Neuroscience
- Vascular Biology
- Pharmacology
Background:
- Cerebral small vessel diseases (CSVDs) are linked to endothelial dysfunction and blood-brain barrier (BBB) damage, with unclear mechanisms and limited treatments.
- Granulocyte-colony stimulating factor (G-CSF) has shown neuroprotective effects in various neurological conditions.
Purpose of the Study:
- To investigate the therapeutic effects of G-CSF on BBB protection and cognitive function in spontaneously hypertensive rats (SHRs), an animal model of early CSVD.
- To explore the impact of G-CSF on endothelial cell structure and key protein expression related to BBB integrity.
Main Methods:
- Spontaneously hypertensive rats (SHRs) received daily G-CSF or saline for 7 days, followed by behavioral testing (novel object recognition test).
- Blood-brain barrier (BBB) integrity was assessed via IgG leakage. Expression of G-CSF receptor (G-CSFR), aquaporin-4 (AQP4), and glial fibrillary acidic protein (GFAP) was analyzed using immunofluorescence. Endothelial cell surface structure was examined by scanning electron microscopy (SEM).
Main Results:
- G-CSF treatment significantly reduced IgG leakage, indicating improved BBB integrity.
- Cognitive function, specifically non-spatial memory, was enhanced in G-CSF treated rats.
- G-CSF administration led to decreased expression of AQP4 and GFAP and normalized endothelial cell surface structure, despite unchanged Claudin-5 levels. G-CSFR expression was elevated in both groups.
Conclusions:
- Exogenous G-CSF administration demonstrates potential in improving cognitive function in a CSVD rat model.
- The findings suggest G-CSF may exert its benefits through the recovery of endothelial and BBB function.
- G-CSF represents a promising therapeutic candidate for neurological disorders characterized by BBB dysfunction.
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.
