title: Combination of fasudil and celecoxib promotes the recovery of injured spinal cord in rats better than celecoxib or fasudil alone.
abstract: Resistance mechanisms of rho-associated kinase (ROCK) inhibitors are associated with the enhanced expression of cyclooxygenase-2 (COX-2). The therapeutic effects of ROCK on nervous system diseases might be enhanced by COX-2 inhibitors. This study investigated the synergistic effect of the combined use of the ROCK inhibitor fasudil and a COX-2 inhibitor celecoxib on spinal cord injury in a rat model established by transecting the right half of the spinal cord at T11. Rat models were orally administrated with celecoxib (20 mg/kg) and/or intramuscularly with fasudil (10 mg/kg) for 2 weeks. Results demonstrated that the combined use of celecoxib and fasudil significantly decreased COX-2 and Rho kinase II expression surrounding the lesion site in rats with spinal cord injury, improved the pathomorphology of the injured spinal cord, and promoted the recovery of motor function. Moreover, the effects of the drug combination were better than celecoxib or fasudil alone. This study demonstrated that the combined use of fasudil and celecoxib synergistically enhanced the functional recovery of injured spinal cord in rats.
authors.affiliation: Key Laboratory of Molecular Biology for Sinomedicine, Yunnan Key Laboratory for Enthnomedicine, Kunming, Yunnan Province, China.
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Hou
authors.affiliation: Key Laboratory of Molecular Biology for Sinomedicine, Yunnan Key Laboratory for Enthnomedicine, Kunming, Yunnan Province, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Laboratory of Molecular Biology for Sinomedicine, Yunnan Key Laboratory for Enthnomedicine, Kunming, Yunnan Province, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yin
authors.affiliation: Key Laboratory of Molecular Biology for Sinomedicine, Yunnan Key Laboratory for Enthnomedicine, Kunming, Yunnan Province, China; Initiative Team of Microenvironment, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan Province, China.
authors.forename: Wei-Gang
authors.identifier: 0000-0002-9006-861X
authors.initials: WG
authors.lastname: Duan
keywords: NSFC grant; Rho kinase; celecoxib; cyclooxygenase-2; fasudil; nerve regeneration; neural regeneration; spinal cord injury