Rolipram-loaded PgP nanoparticle reduces secondary injury and enhances motor function recovery in a rat moderate contusion SCI model.

Spinal cord injury (SCI) results in immediate axonal damage and cell death, as well as a prolonged secondary injury consist of a cascade of pathophysiological processes. One important aspect of secondary injury is activation of phosphodiesterase 4 (PDE4) that leads to reduce cAMP levels in the injured spinal cord. We have developed an amphiphilic copolymer, poly (lactide-co-glycolide)-graft-polyethylenimine (PgP) that can deliver Rolipram, the PDE4 inhibitor. The objective of this work was to investigate the effect of rolipram loaded PgP (Rm-PgP) on secondary injury and motor functional recovery in a rat moderate contusion SCI model. We observed that Rm-PgP can increase cAMP level at the lesion site, and reduce secondary injury such as the inflammatory response by macrophages/microglia, astrogliosis by activated astrocytes and apoptosis as well as improve neuronal survival at 4 weeks post-injury (WPI). We also observed that Rm-PgP can improve motor functional recovery after SCI over 4 WPI. The therapeutic efficacy of a polymeric micellar nanocarrier [poly (lactide-co-glycolide-graft-polyethylenimine); PgP] loaded with rolipram (Rm), a phosphodiesterase IV inhibitor, was investigated in a rat moderate thoracic contusion SCI model. Rm-PgP administered by single intraspinal injection mitigated acute injury-induced decline in cyclic AMP (cAMP) levels and reduced astrogliosis, inflammatory cell activation, and apoptosis; and improved motor function recovery at 4 weeks post-injury. [Display omitted] [ABSTRACT FROM AUTHOR]