Contrary to lower species that recapitulate some of the developmental programs, in mammals, functional recovery after spinal cord injury is impaired by a non-permissive environment and the lack of plasticity of adult neurons. The developmental plasticity associated linear homopolymer of alpha 2,8-linked sialic acid (PolySialic Acid, PSA), represents a permissive determinant that could contribute to recovery. We previously showed that a PSA cyclic mimetic peptide (PR-21) displayed PSA-like biological functions (Torregrossa, P., Buhl, L., Bancila, M., Durbec, P., Schafer, C., Schachner, M., Rougon, G., 2004. Selection of poly-alpha 2,8-sialic acid mimotopes from a random phage peptide library and analysis of their bioactivity. J. Biol. Chem. 279, 30707-30714.). In the present study we investigated the therapeutic potential of PR-21 in young adult mice after dorsal hemisection at the T9 level. We show that PR-21 fulfills several criteria for an in vivo use as it is not toxic, not immunogenic and displays good stability in biological fluids or tissue. Delivery of PR-21 to the lesion site decreased the time of the animals' return to continence, and enhanced motor functions, sensorimotor control and coordination of hindlimbs with forelimbs when compared to a control peptide. At the cellular level, PR-21 increased serotonergic axon density at and caudal to the lesion site, and decreased reactive gliosis in vivo. In an in vitro model of reactive astrocytes, PR-21 increased NCAM expression in strongly GFAP positive cells. Our data point to the unique features of a carbohydrate mimicking peptide, and support the notion that PSA can be considered as an important factor in recovery from spinal cord injury.
Contrary to lower species that recapitulate some of the developmental programs, in mammals, functional recovery after spinal cord injury is impaired by a non-permissive environment and the lack of plasticity of adult neurons. The developmental plasticity associated linear homopolymer of alpha 2,8-linked sialic acid (PolySialic Acid, PSA), represents a permissive determinant that could contribute to recovery. We previously showed that a PSA cyclic mimetic peptide (PR-21) displayed PSA-like biological functions (Torregrossa, P., Buhl, L., Bancila, M., Durbec, P., Schafer, C., Schachner, M., Rougon, G., 2004. Selection of poly-alpha 2,8-sialic acid mimotopes from a random phage peptide library and analysis of their bioactivity. J. Biol. Chem. 279, 30707-30714.). In the present study we investigated the therapeutic potential of PR-21 in young adult mice after dorsal hemisection at the T9 level. We show that PR-21 fulfills several criteria for an in vivo use as it is not toxic, not immunogenic and displays good stability in biological fluids or tissue. Delivery of PR-21 to the lesion site decreased the time of the animals' return to continence, and enhanced motor functions, sensorimotor control and coordination of hindlimbs with forelimbs when compared to a control peptide. At the cellular level, PR-21 increased serotonergic axon density at and caudal to the lesion site, and decreased reactive gliosis in vivo. In an in vitro model of reactive astrocytes, PR-21 increased NCAM expression in strongly GFAP positive cells. Our data point to the unique features of a carbohydrate mimicking peptide, and support the notion that PSA can be considered as an important factor in recovery from spinal cord injury.