Carbohydrate mimics promote functional recovery after peripheral nerve repair.
OBJECTIVE
The outcome of peripheral nerve repair is often unsatisfactory, and efficient therapies are not available. We tested the therapeutic potential of functional mimics of the human natural killer cell glycan (3-sulfoglucuronyl beta1-3 galactoside) (HNK-1) epitope, a carbohydrate indicated to favor specificity of motor reinnervation in mice.


METHODS
We applied a linear HNK-1 mimic peptide, scrambled peptide, or vehicle substances in polyethylene cuffs used to reconstruct the severed femoral nerves of adult mice. We used video-based motion analysis and morphological and tracing techniques to monitor the outcome of nerve repair.


RESULTS
After glycomimetic application, quadriceps muscle function recovered to 93% of normal within 3 months. Restoration of function was less complete (71-76%) in control groups. Better functional recovery was associated with larger motoneuron somata, better axonal myelination in the quadriceps nerve, and enhanced precision of target reinnervation. Lesion-induced death of motoneurons was reduced by 20 to 25%. The glycomimetic enhanced survival and neurite outgrowth of both mouse and human motoneurons in vitro by 30 to 75%. Application of a novel cyclic glycomimetic also enhanced functional recovery in vivo.


CONCLUSIONS
The improved outcome of nerve repair after glycomimetic application may be attributed to neurotrophic effects. Our results hold promise for therapeutic use in humans.
Simova
Olga
O
Zentrum für Molekulare Neurobiologie, Universität Hamburg, Hamburg, Germany.
Irintchev
Andrey
A
Mehanna
Ali
A
Liu
Jiankun
J
Dihné
Marcel
M
Bächle
Dirk
D
Sewald
Norbert
N
Loers
Gabriele
G
Schachner
Melitta
M
D000818:Animals; D001369:Axons / Q000502:physiology; D018959:CD57 Antigens / Q000494:pharmacology* / Q000502:physiology*; D002241:Carbohydrates / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D000939:Epitopes / Q000235:genetics; D051379:Mice; D018716:Molecular Mimicry; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000294:innervation; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D010525:Peripheral Nerves / Q000473:pathology / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology
D018959:CD57 Antigens; D002241:Carbohydrates; D000939:Epitopes