title: Carvedilol promotes neurological function, reduces bone loss and attenuates cell damage after acute spinal cord injury in rats.
abstract: Acute spinal cord injury (SCI) leads to permanent functional deficits via mechanical injury and secondary mechanisms, but the therapeutic strategy for SCI is limited. Carvedilol has been shown to possess multiple biological and pharmacological properties. The of the present study was to investigate the possible protective effect of carvedilol in SCI rats. An acute SCI rat model was established and neurological function was tested. After carvedilol (10 mg/kg, oral gavage) treatment for 21 days, the status of osteoporosis, neuron damage, astrocyte activation, inflammation, oxidative stress and apoptosis were evaluated in rats. Carvedilol significantly improved locomotor activity that was decreased by SCI. In addition, carvedilol promoted bone growth by regulating the expression of nuclear factor-κB ligand (receptor activator of nuclear factor-κB ligand; RANKL) and osteoprotegerin (OPG), inactivating osteoclasts and thereby increasing bone mineral density in tibias. In addition, carvedilol reduced SCI-induced neural damage, increased neuron number and reduced astrocyte activation in the spinal cord. Furthermore, the production and mRNA expression of tumour necrosis factor-α, interleukin (IL)-1β and IL-6 were significantly reduced, reduced glutathione content and superoxide dismutase activity were markedly increased and malondialdehyde content was markedly decreased in the spinal cords of carvedilol-treated rats. These results indicate that carvedilol exhibits anti-inflammatory and anti-oxidative effects in SCI rats. In addition, the expression of Fas and Fas ligand was reduced by carvedilol treatment, which, in turn, reduced cleaved caspase 3 expression and finally decreased the number of apoptotic cells in the spinal cord. In conclusion, carvedilol promotes neurological function, reduces bone loss and attenuates cell damage after acute SCI in rats.
authors.affiliation: Department of Orthopaedic Surgery, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Da
authors.initials: D
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Changqing
authors.initials: C
authors.lastname: Jia
authors.forename: Feng
authors.initials: F
authors.lastname: Liang
authors.forename: Qin
authors.initials: Q
authors.lastname: Fu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D053148:Caspase 3 / Q000378:metabolism; D053222:Fas Ligand Protein / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D010024:Osteoporosis / Q000188:drug therapy* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology*; D053245:RANK Ligand / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
chemical_list: D002227:Carbazoles; D053222:Fas Ligand Protein; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D011412:Propanolamines; D053245:RANK Ligand; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D000077261:Carvedilol; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D053148:Caspase 3; D005978:Glutathione
keywords: acute spinal cord injury; apoptosis; carvedilol; inflammatory response; osteoporosis; oxidative stress