Cerebral small vessel disease (CSVD) is a group of diseases that originate from changes in
cerebral small vessels and that cause many conditions, such as cognitive impairment. However, there
is no effective therapy for these diseases. Recent studies have suggested that inflammation is associated
with this disease. Cyclooxygenase-2 (cox-2) is an inflammatory mediator; however, whether a
cox-2 inhibitor could protect against the CSVD progression remains unknown. In the present study,
stroke-prone spontaneously hypertensive rats (SHRsp) were used as a model of CSVD, and Sprague
Dawley (SD) rats served as the control. SHRsp were treated with the cox-2 inhibitor celecoxib or vehicle. The Morris water
maze test was performed, and vascular morphometry and the expression of collagen I and fibronectin were examined
in cerebral small vessels and cerebral tissue. The results revealed that thickened small veesel walls, increased expression
of collagen I and fibronectin and impaired cognitive function in SHRsp compared with SD rats. Additionally, celecoxib
significantly down-regulated the expression of collagen I and fibronectin, attenuated the increase in vascular wall thickness
and ameliorates the cognitive impairment. Our study indicated that this cox-2 inhibitor may serve as a promising
candidate for the pharmacological intervention of CSVD.
Keywords: Cerebral small vessel disease, cognitive impairment, collagen I, cyclooxygenase-2, fibronectin, hypertension.
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