title: A Cyclooxygenase-2 Inhibitor Reduces Vascular Wall Thickness and Ameliorates Cognitive Impairment in a Cerebral Small Vessel Diseases Rat Model.
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.
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.forename: Weizhong
authors.initials: W
authors.lastname: Xiao
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Li
authors.forename: Qiuqiong
authors.initials: Q
authors.lastname: Deng
authors.forename: Xinquan
authors.initials: X
authors.lastname: Chu
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.forename: Danhong
authors.initials: D
authors.lastname: Pan
authors.affiliation: Department of Neurology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Pudong, Shanghai 201399, China. jianhuifu@126.com.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Fu
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D000068579:Celecoxib / Q000494:pharmacology*; D059345:Cerebral Small Vessel Diseases / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D003072:Cognition Disorders / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D024042:Collagen Type I / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D005353:Fibronectins / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D009929:Organ Size; D012333:RNA, Messenger / Q000378:metabolism; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley
chemical_list: D024042:Collagen Type I; D052246:Cyclooxygenase 2 Inhibitors; D005353:Fibronectins; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D000068579:Celecoxib