title: Rolipram promotes functional recovery after contusive thoracic spinal cord injury in rats.
abstract: Numerous animal model studies in the past decade have demonstrated that pharmacological elevation of cyclic AMP (cAMP) alone, or in combination with other treatments, can promote axonal regeneration after spinal cord injury. Elevation of cAMP via the phosphodiesterase 4 (PDE4) inhibitor, rolipram, decreases neuronal sensitivity to myelin inhibitors, increases growth potential and is neuroprotective. Rolipram's ability to cross the blood-brain barrier makes it a practical and promising treatment for CNS regeneration. However, several studies have questioned the efficacy of rolipram when given alone. The purpose of this investigation was to determine the effects of continuous administration of rolipram, given alone for 2 weeks, following a moderate T10 contusion injury in rat. Functional recovery was evaluated using the 21-point Basso, Beattie and Bresnahan (BBB) locomotor recovery scale and the beam walk. We used three-dimensional (3D) instrumented gait analysis to allow detailed assessment and quantification of hindlimb motion. The amount of the damaged tissue and spared white matter was estimated stereologically. Our results show that administration of rolipram following acute spinal cord contusion results in improved motor performance at each time-point. Dynamic assessment of foot motion during treadmill walking revealed a significantly decreased external rotation during the entire step cycle after 8 weeks in rolipram-treated animals. Stereological analysis revealed no significant differences in lesion volume and length. By contrast, spared white matter was significantly higher in the group treated with rolipram. Our results suggest a therapeutic role for rolipram delivered alone following acute SCI.
authors.affiliation: Department of Veterinary Sciences, CIDESD, University of Trás-os-Montes e Alto Douro, PO Box 1013, 5001-801 Vila Real, Portugal.
authors.forename: Luís M
authors.initials: LM
authors.lastname: Costa
authors.forename: José E
authors.initials: JE
authors.lastname: Pereira
authors.forename: Vítor M
authors.initials: VM
authors.lastname: Filipe
authors.forename: Luís G
authors.initials: LG
authors.lastname: Magalhães
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Couto
authors.forename: José M
authors.initials: JM
authors.lastname: Gonzalo-Orden
authors.forename: Stefania
authors.initials: S
authors.lastname: Raimondo
authors.forename: Stefano
authors.initials: S
authors.lastname: Geuna
authors.forename: Ana C
authors.initials: AC
authors.lastname: Maurício
authors.forename: Elena
authors.initials: E
authors.lastname: Nikulina
authors.forename: Marie T
authors.initials: MT
authors.lastname: Filbin
authors.forename: Artur S P
authors.initials: AS
authors.lastname: Varejão
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005260:Female; D015918:Infusion Pumps, Implantable; D009043:Motor Activity / Q000187:drug effects; D058988:Phosphodiesterase 4 Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects*; D020889:Rolipram / Q000008:administration & dosage / Q000494:pharmacology*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D013904:Thoracic Vertebrae / Q000601:surgery; D016896:Treatment Outcome
chemical_list: D058988:Phosphodiesterase 4 Inhibitors; D020889:Rolipram