Polysialic acid glycomimetic promotes functional recovery and plasticity after spinal cord injury in mice

Ali Mehanna, Igor Jakovcevski, Aye Acar, Meifang Xiao, Gabriele Loers, Geneviève Rougon, Andrey Irintchev, Melitta Schachner

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)34-43
Number of pages10
JournalMolecular Therapy
Volume18
Issue number1
DOIs
StatePublished - Jan 2010
Externally publishedYes

Fingerprint

Spinal Cord Injuries
Natural Killer Cells
Regeneration
Spinal Cord
Wounds and Injuries
Thoracic Injuries
Peptides
Presynaptic Terminals
Inbred C57BL Mouse
Cholinergic Agents
Polysaccharides
polysialic acid
Epitopes
Young Adult
Central Nervous System
Carbohydrates
Observation
Therapeutics
Growth

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Cite this

Polysialic acid glycomimetic promotes functional recovery and plasticity after spinal cord injury in mice. / Mehanna, Ali; Jakovcevski, Igor; Acar, Aye; Xiao, Meifang; Loers, Gabriele; Rougon, Geneviève; Irintchev, Andrey; Schachner, Melitta.

In: Molecular Therapy, Vol. 18, No. 1, 01.2010, p. 34-43.

Research output: Contribution to journalArticle

Mehanna, A, Jakovcevski, I, Acar, A, Xiao, M, Loers, G, Rougon, G, Irintchev, A & Schachner, M 2010, 'Polysialic acid glycomimetic promotes functional recovery and plasticity after spinal cord injury in mice', Molecular Therapy, vol. 18, no. 1, pp. 34-43. https://doi.org/10.1038/mt.2009.235
Mehanna, Ali ; Jakovcevski, Igor ; Acar, Aye ; Xiao, Meifang ; Loers, Gabriele ; Rougon, Geneviève ; Irintchev, Andrey ; Schachner, Melitta. / Polysialic acid glycomimetic promotes functional recovery and plasticity after spinal cord injury in mice. In: Molecular Therapy. 2010 ; Vol. 18, No. 1. pp. 34-43.
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