Polysialic acid glycomimetic promotes functional recovery and plasticity after spinal cord injury in mice.
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Polysialic acid glycomimetic promotes functional recovery and plasticity after spinal cord injury in mice. / Mehanna, Ali; Jakovcevski, Igor; Acar, Ayse; Xiao, Meifang; Loers, Gabriele; Rougon, Geneviève; Irintchev, Andrey; Schachner, Melitta.
in: MOL THER, Jahrgang 18, Nr. 1, 1, 2010, S. 34-43.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Polysialic acid glycomimetic promotes functional recovery and plasticity after spinal cord injury in mice.
AU - Mehanna, Ali
AU - Jakovcevski, Igor
AU - Acar, Ayse
AU - Xiao, Meifang
AU - Loers, Gabriele
AU - Rougon, Geneviève
AU - Irintchev, Andrey
AU - Schachner, Melitta
PY - 2010
Y1 - 2010
N2 - Regeneration after injury of the central nervous system is poor due to the abundance of molecules inhibiting axonal growth. Here we pursued to promote regeneration after thoracic spinal cord injury in young adult C57BL/6J mice using peptides which functionally mimic polysialic acid (PSA) and human natural killer cell-1 (HNK-1) glycan, carbohydrate epitopes known to promote neurite outgrowth in vitro. Subdural infusions were performed with an osmotic pump, over 2 weeks. When applied immediately after injury, the PSA mimetic and the combination of PSA and HNK-1 mimetics, but not the HNK-1 mimetic alone, improved functional recovery as assessed by locomotor rating and video-based motion analysis over a 6-week observation period. Better outcome in PSA mimetic-treated mice was associated with higher, as compared with control mice, numbers of cholinergic and glutamatergic terminals and monaminergic axons in the lumbar spinal cord, and better axonal myelination proximal to the injury site. In contrast to immediate post-traumatic application, the PSA mimetic treatment was ineffective when initiated 3 weeks after spinal cord injury. Our data suggest that PSA mimetic peptides can be efficient therapeutic tools improving, by augmenting plasticity, functional recovery when applied during the acute phase of spinal cord injury.
AB - Regeneration after injury of the central nervous system is poor due to the abundance of molecules inhibiting axonal growth. Here we pursued to promote regeneration after thoracic spinal cord injury in young adult C57BL/6J mice using peptides which functionally mimic polysialic acid (PSA) and human natural killer cell-1 (HNK-1) glycan, carbohydrate epitopes known to promote neurite outgrowth in vitro. Subdural infusions were performed with an osmotic pump, over 2 weeks. When applied immediately after injury, the PSA mimetic and the combination of PSA and HNK-1 mimetics, but not the HNK-1 mimetic alone, improved functional recovery as assessed by locomotor rating and video-based motion analysis over a 6-week observation period. Better outcome in PSA mimetic-treated mice was associated with higher, as compared with control mice, numbers of cholinergic and glutamatergic terminals and monaminergic axons in the lumbar spinal cord, and better axonal myelination proximal to the injury site. In contrast to immediate post-traumatic application, the PSA mimetic treatment was ineffective when initiated 3 weeks after spinal cord injury. Our data suggest that PSA mimetic peptides can be efficient therapeutic tools improving, by augmenting plasticity, functional recovery when applied during the acute phase of spinal cord injury.
M3 - SCORING: Zeitschriftenaufsatz
VL - 18
SP - 34
EP - 43
JO - MOL THER
JF - MOL THER
SN - 1525-0016
IS - 1
M1 - 1
ER -
