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A Cyclooxygenase-2 Inhibitor Reduces Vascular Wall Thickness and Ameliorates Cognitive Impairment in a Cerebral Small Vessel Diseases Rat Model

[ Vol. 12 , Issue. 7 ]

Author(s):

Jie Tang, Weizhong Xiao, Qinghua Li, Qiuqiong Deng, Xinquan Chu, Yang Chen, Danhong Pan and Jianhui Fu   Pages 704 - 710 ( 7 )

Abstract:


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.

Affiliation:

, , , , , , , Department of Neurology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Pudong, Shanghai 201399, China.



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