title: Effects of combining methylprednisolone with rolipram on functional recovery in adult rats following spinal cord injury.
abstract: Methylprednisolone (MP) has been widely used as a standard therapeutic agent for the treatment of spinal cord injury (SCI). Because of its controversial beneficial effects, the combination of MP and other pharmacological agents aimed at enhancing functional recovery is desirable. The phosphodiesterase 4 (PDE4) inhibitor rolipram has been implicated in promotion of regeneration due to elevating cAMP. In the present study, we sought to determine the effects of MP and rolipram, administered in combination, after spinal cord injury (SCI) in adult rats. Here we show that in vitro administration of rolipram and MP significantly increased neuron survival and promoted neurite outgrowth of neurons on the inhibitory substrate CSPGs by upregulation of MMP-2 expression; in vivo administration of rolipram and MP inhibited CSPG expression and increase CSPG digestion after rat SCI. Rolipram and MP combining treatment promoted significant neuroprotection through reduced motoneuron death, minimized lesion cavity, and increased regeneration of lesioned corticospinal tract (CST) axons beyond the lesion site after SCI. Enhanced functional recovery was also observed. Overall, our study strongly suggested that the combination treatment of MP and rolipram may represent a promising strategy for clinically applicable pharmacological therapy for rapid initiation of neuroprotection after SCI.
authors.affiliation: Department of Clinical Laboratory Science, Wuxi People's Hospital of Nanjing Medical University, Wuxi, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yin
authors.forename: Weifeng
authors.initials: W
authors.lastname: Sun
authors.forename: Zaiwang
authors.initials: Z
authors.lastname: Li
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: Hua
authors.initials: H
authors.lastname: Cui
authors.forename: Lingxiao
authors.initials: L
authors.lastname: Deng
authors.forename: Ping
authors.initials: P
authors.lastname: Xie
authors.forename: Jie
authors.initials: J
authors.lastname: Xiang
authors.forename: Jian
authors.initials: J
authors.lastname: Zou
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D008775:Methylprednisolone / Q000627:therapeutic use*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*; D020889:Rolipram / Q000008:administration & dosage / Q000627:therapeutic use*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
chemical_list: D018696:Neuroprotective Agents; D020889:Rolipram; D008775:Methylprednisolone