Carbohydrate mimics promote functional recovery after peripheral nerve repair

Simova O, Irintchev A, Mehanna A, Liu J, Dihne M, Baechle D, Sewald N, Loers G, Schachner M (2006)
ANNALS OF NEUROLOGY 60(4): 430-437.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
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Simova, Olga; Irintchev, Andrey; Mehanna, Ali; Liu, Jiankun; Dihne, Marcel; Baechle, Dirk; Sewald, NorbertUniBi ; Loers, Gabriele; Schachner, Melitta
Abstract / Bemerkung
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 beta 1-3 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. Interpretation: The improved outcome of nerve repair after glycomimetic application may be attributed to neurotrophic effects. Our results hold promise for therapeutic use in humans.
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Simova O, Irintchev A, Mehanna A, et al. Carbohydrate mimics promote functional recovery after peripheral nerve repair. ANNALS OF NEUROLOGY. 2006;60(4):430-437.
Simova, O., Irintchev, A., Mehanna, A., Liu, J., Dihne, M., Baechle, D., Sewald, N., et al. (2006). Carbohydrate mimics promote functional recovery after peripheral nerve repair. ANNALS OF NEUROLOGY, 60(4), 430-437.
Simova, Olga, Irintchev, Andrey, Mehanna, Ali, Liu, Jiankun, Dihne, Marcel, Baechle, Dirk, Sewald, Norbert, Loers, Gabriele, and Schachner, Melitta. 2006. “Carbohydrate mimics promote functional recovery after peripheral nerve repair”. ANNALS OF NEUROLOGY 60 (4): 430-437.
Simova, O., Irintchev, A., Mehanna, A., Liu, J., Dihne, M., Baechle, D., Sewald, N., Loers, G., and Schachner, M. (2006). Carbohydrate mimics promote functional recovery after peripheral nerve repair. ANNALS OF NEUROLOGY 60, 430-437.
Simova, O., et al., 2006. Carbohydrate mimics promote functional recovery after peripheral nerve repair. ANNALS OF NEUROLOGY, 60(4), p 430-437.
O. Simova, et al., “Carbohydrate mimics promote functional recovery after peripheral nerve repair”, ANNALS OF NEUROLOGY, vol. 60, 2006, pp. 430-437.
Simova, O., Irintchev, A., Mehanna, A., Liu, J., Dihne, M., Baechle, D., Sewald, N., Loers, G., Schachner, M.: Carbohydrate mimics promote functional recovery after peripheral nerve repair. ANNALS OF NEUROLOGY. 60, 430-437 (2006).
Simova, Olga, Irintchev, Andrey, Mehanna, Ali, Liu, Jiankun, Dihne, Marcel, Baechle, Dirk, Sewald, Norbert, Loers, Gabriele, and Schachner, Melitta. “Carbohydrate mimics promote functional recovery after peripheral nerve repair”. ANNALS OF NEUROLOGY 60.4 (2006): 430-437.

44 Zitationen in Europe PMC

Daten bereitgestellt von Europe PubMed Central.

Cell Adhesion Molecule Close Homolog of L1 (CHL1) Guides the Regrowth of Regenerating Motor Axons and Regulates Synaptic Coverage of Motor Neurons.
Guseva D, Jakovcevski I, Irintchev A, Leshchyns'ka I, Sytnyk V, Ponimaskin E, Schachner M., Front Mol Neurosci 11(), 2018
PMID: 29881335
HNK-1 Carrier Glycoproteins Are Decreased in the Alzheimer's Disease Brain.
García-Ayllón MS, Botella-López A, Cuchillo-Ibañez I, Rábano A, Andreasen N, Blennow K, Ávila J, Sáez-Valero J., Mol Neurobiol 54(1), 2017
PMID: 26738850
Myelin Basic Protein Cleaves Cell Adhesion Molecule L1 and Improves Regeneration After Injury.
Lutz D, Kataria H, Kleene R, Loers G, Chaudhary H, Guseva D, Wu B, Jakovcevski I, Schachner M., Mol Neurobiol 53(5), 2016
PMID: 26081148
Small Molecule Agonists of Cell Adhesion Molecule L1 Mimic L1 Functions In Vivo.
Kataria H, Lutz D, Chaudhary H, Schachner M, Loers G., Mol Neurobiol 53(7), 2016
PMID: 26253722
Vinorelbine and epirubicin share common features with polysialic acid and modulate neuronal and glial functions.
Loers G, Saini V, Mishra B, Gul S, Chaudhury S, Wallqvist A, Kaur G, Schachner M., J Neurochem 136(1), 2016
PMID: 26443186
Porous and Nonporous Nerve Conduits: The Effects of a Hydrogel Luminal Filler With and Without a Neurite-Promoting Moiety.
Ezra M, Bushman J, Shreiber D, Schachner M, Kohn J., Tissue Eng Part A 22(9-10), 2016
PMID: 27102571
Glycosaminoglycans and glycomimetics in the central nervous system.
Rowlands D, Sugahara K, Kwok JC., Molecules 20(3), 2015
PMID: 25706756
Tegaserod mimics the neurostimulatory glycan polysialic acid and promotes nervous system repair.
Bushman J, Mishra B, Ezra M, Gul S, Schulze C, Chaudhury S, Ripoll D, Wallqvist A, Kohn J, Schachner M, Loers G., Neuropharmacology 79(), 2014
PMID: 24067923
Improved regeneration after femoral nerve injury in mice lacking functional T- and B-lymphocytes.
Mehanna A, Szpotowicz E, Schachner M, Jakovcevski I., Exp Neurol 261(), 2014
PMID: 24967682
Motoneuron regeneration accuracy and recovery of gait after femoral nerve injuries in rats.
Kruspe M, Thieme H, Guntinas-Lichius O, Irintchev A., Neuroscience 280(), 2014
PMID: 25220899
Dermatan 4-O-sulfotransferase1 ablation accelerates peripheral nerve regeneration.
Akyüz N, Rost S, Mehanna A, Bian S, Loers G, Oezen I, Mishra B, Hoffmann K, Guseva D, Laczynska E, Irintchev A, Jakovcevski I, Schachner M., Exp Neurol 247(), 2013
PMID: 23360803
Deficient functional recovery after facial nerve crush in rats is associated with restricted rearrangements of synaptic terminals in the facial nucleus.
Hundeshagen G, Szameit K, Thieme H, Finkensieper M, Angelov DN, Guntinas-Lichius O, Irintchev A., Neuroscience 248(), 2013
PMID: 23806716
Gold nanoparticles functionalized with a fragment of the neural cell adhesion molecule L1 stimulate L1-mediated functions.
Schulz F, Lutz D, Rusche N, Bastús NG, Stieben M, Höltig M, Grüner F, Weller H, Schachner M, Vossmeyer T, Loers G., Nanoscale 5(21), 2013
PMID: 24056775
Inhibition of the bacterial lectins of Pseudomonas aeruginosa with monosaccharides and peptides.
Gustke H, Kleene R, Loers G, Nehmann N, Jaehne M, Bartels KM, Jaeger KE, Schachner M, Schumacher U., Eur J Clin Microbiol Infect Dis 31(2), 2012
PMID: 21604096
Neural cell type-specific responses to glycomimetic functionalized collagen.
Masand SN, Perron IJ, Schachner M, Shreiber DI., Biomaterials 33(3), 2012
PMID: 22027596
The effect of glycomimetic functionalized collagen on peripheral nerve repair.
Masand SN, Chen J, Perron IJ, Hammerling BC, Loers G, Schachner M, Shreiber DI., Biomaterials 33(33), 2012
PMID: 22917737
Positively and negatively modulating cell adhesion to type I collagen via peptide grafting.
Monteiro GA, Fernandes AV, Sundararaghavan HG, Shreiber DI., Tissue Eng Part A 17(13-14), 2011
PMID: 19196133
Glycomimetic improves recovery after femoral injury in a non-human primate.
Irintchev A, Wu MM, Lee HJ, Zhu H, Feng YP, Liu YS, Bernreuther C, Loers G, You SW, Schachner M., J Neurotrauma 28(7), 2011
PMID: 21463132
Polysialic acid glycomimetic promotes functional recovery and plasticity after spinal cord injury in mice.
Mehanna A, Jakovcevski I, Acar A, Xiao M, Loers G, Rougon G, Irintchev A, Schachner M., Mol Ther 18(1), 2010
PMID: 19826404
Functional role of the interaction between polysialic acid and extracellular histone H1.
Mishra B, von der Ohe M, Schulze C, Bian S, Makhina T, Loers G, Kleene R, Schachner M., J Neurosci 30(37), 2010
PMID: 20844135
Functional effects of local thyroid hormone administration after sciatic nerve injury in rats.
Papakostas I, Mourouzis I, Mourouzis K, Macheras G, Boviatsis E, Pantos C., Microsurgery 29(1), 2009
PMID: 18942650
Lewis(x) and alpha2,3-sialyl glycans and their receptors TAG-1, Contactin, and L1 mediate CD24-dependent neurite outgrowth.
Lieberoth A, Splittstoesser F, Katagihallimath N, Jakovcevski I, Loers G, Ranscht B, Karagogeos D, Schachner M, Kleene R., J Neurosci 29(20), 2009
PMID: 19458237
Polysialic acid glycomimetics promote myelination and functional recovery after peripheral nerve injury in mice.
Mehanna A, Mishra B, Kurschat N, Schulze C, Bian S, Loers G, Irintchev A, Schachner M., Brain 132(pt 6), 2009
PMID: 19454531
Chemical communication between regenerating motor axons and Schwann cells in the growth pathway.
Vrbova G, Mehra N, Shanmuganathan H, Tyreman N, Schachner M, Gordon T., Eur J Neurosci 30(3), 2009
PMID: 19656172
Accelerating axon growth to overcome limitations in functional recovery after peripheral nerve injury.
Gordon T, Chan KM, Sulaiman OA, Udina E, Amirjani N, Brushart TM., Neurosurgery 65(4 suppl), 2009
PMID: 19927058
The impact of motor and sensory nerve architecture on nerve regeneration.
Moradzadeh A, Borschel GH, Luciano JP, Whitlock EL, Hayashi A, Hunter DA, Mackinnon SE., Exp Neurol 212(2), 2008
PMID: 18550053
Manual stimulation of the suprahyoid-sublingual region diminishes polynnervation of the motor endplates and improves recovery of function after hypoglossal nerve injury in rats.
Evgenieva E, Schweigert P, Guntinas-Lichius O, Pavlov S, Grosheva M, Angelova S, Streppel M, Irintchev A, Skouras E, Kuerten S, Sinis N, Dunlop S, Radeva V, Angelov DN., Neurorehabil Neural Repair 22(6), 2008
PMID: 18612142
Recognition molecules and neural repair.
Loers G, Schachner M., J Neurochem 101(4), 2007
PMID: 17254012
One hour electrical stimulation accelerates functional recovery after femoral nerve repair.
Ahlborn P, Schachner M, Irintchev A., Exp Neurol 208(1), 2007
PMID: 17919580
Differential expression of HNK-1 and p75(NTR) in adult canine Schwann cells and olfactory ensheathing cells in situ but not in vitro.
Bock P, Beineke A, Techangamsuwan S, Baumgärtner W, Wewetzer K., J Comp Neurol 505(5), 2007
PMID: 17924534

50 References

Daten bereitgestellt von Europe PubMed Central.

Peripheral nerve injury and repair.
Lee SK, Wolfe SW., J Am Acad Orthop Surg 8(4), 2000
PMID: 10951113
Traumatic injury to peripheral nerves.
Robinson LR., Muscle Nerve 23(6), 2000
PMID: 10842261
Aberrant reinnervation.
Sumner AJ., Muscle Nerve 13(9), 1990
PMID: 2233866
Motor axons preferentially reinnervate motor pathways.
Brushart TM., J. Neurosci. 13(6), 1993
PMID: 8501535
Reinnervation accuracy of the rat femoral nerve by motor and sensory neurons.
Madison RD, Archibald SJ, Brushart TM., J. Neurosci. 16(18), 1996
PMID: 8795625
Recognition molecule associated carbohydrate inhibits postsynaptic GABA(B) receptors: a mechanism for homeostatic regulation of GABA release in perisomatic synapses.
Saghatelyan AK, Snapyan M, Gorissen S, Meigel I, Mosbacher J, Kaupmann K, Bettler B, Kornilov AV, Nifantiev NE, Sakanyan V, Schachner M, Dityatev A., Mol. Cell. Neurosci. 24(2), 2003
PMID: 14572452
Identification of a peptide mimic of the L2/HNK-1 carbohydrate epitope.
Simon-Haldi M, Mantei N, Franke J, Voshol H, Schachner M., J. Neurochem. 83(6), 2002
PMID: 12472892
Antibodies to myelin-associated glycoprotein accelerate preferential motor reinnervation.
Mears S, Schachner M, Brushart TM., J. Peripher. Nerv. Syst. 8(2), 2003
PMID: 12795713
Altered expression of immune-related antigens by neuronophages does not improve neuronal survival after severe lesion of the facial nerve in rats.
Angelov DN, Krebs C, Walther M, Martinez-Portillo FJ, Gunkel A, Lay CH, Streppel M, Guntinas-Lichius O, Stennert E, Neiss WF., Glia 24(2), 1998
PMID: 9728762
Displacement of synaptic terminals from regenerating motoneurons by microglial cells.
Blinzinger K, Kreutzberg G., Z Zellforsch Mikrosk Anat 85(2), 1968
PMID: 5706753
The facial nerve axotomy model.
Moran LB, Graeber MB., Brain Res. Brain Res. Rev. 44(2-3), 2004
PMID: 15003391
Large cholinergic nerve terminals on subsets of motoneurons and their relation to muscarinic receptor type 2.
Hellstrom J, Oliveira AL, Meister B, Cullheim S., J. Comp. Neurol. 460(4), 2003
PMID: 12717708
Changes in synaptology of adult cat spinal alpha-motoneurons after axotomy.
Brannstrom T, Kellerth JO., Exp Brain Res 118(1), 1998
PMID: 9547066
BDNF/TrkB signaling regulates HNK-1 carbohydrate expression in regenerating motor nerves and promotes functional recovery after peripheral nerve repair.
Eberhardt KA, Irintchev A, Al-Majed AA, Simova O, Brushart TM, Gordon T, Schachner M., Exp. Neurol. 198(2), 2006
PMID: 16460731
Prion protein as trans-interacting partner for neurons is involved in neurite outgrowth and neuronal survival.
Chen S, Mange A, Dong L, Lehmann S, Schachner M., Mol. Cell. Neurosci. 22(2), 2003
PMID: 12676532
The L2/HNK-1 carbohydrate mediates adhesion of neural cells to laminin.
Hall H, Liu L, Schachner M, Schmitz B., Eur. J. Neurosci. 5(1), 1993
PMID: 8261088
Structural features of a close homologue of L1 (CHL1) in the mouse: a new member of the L1 family of neural recognition molecules.
Holm J, Hillenbrand R, Steuber V, Bartsch U, Moos M, Lubbert H, Montag D, Schachner M., Eur. J. Neurosci. 8(8), 1996
PMID: 8921253
Glycans and neural cell interactions.
Kleene R, Schachner M., Nat. Rev. Neurosci. 5(3), 2004
PMID: 14976519
Neural cell adhesion molecules and myelin-associated glycoprotein share a common carbohydrate moiety recognized by monoclonal antibodies L2 and HNK-1.
Kruse J, Mailhammer R, Wernecke H, Faissner A, Sommer I, Goridis C, Schachner M., Nature 311(5982), 1984
PMID: 6206400
Sulfoglycolipids bind to adhesive protein amphoterin (P30) in the nervous system.
Mohan PS, Laitinen J, Merenmies J, Rauvala H, Jungalwala FB., Biochem. Biophys. Res. Commun. 182(2), 1992
PMID: 1370890
Heat-stable antigen (mouse CD24) in the brain: dual but distinct interaction with P-selectin and L1.
Sammar M, Aigner S, Altevogt P., Biochim. Biophys. Acta 1337(2), 1997
PMID: 9048906
Glycans and the modulation of neural-recognition molecule function.
Schachner M, Martini R., Trends Neurosci. 18(4), 1995
PMID: 7539963
Chromatin and cell death.
Bianchi ME, Manfredi A., Biochim. Biophys. Acta 1677(1-3), 2004
PMID: 15020058
HMGB1: guiding immunity from within.
Dumitriu IE, Baruah P, Manfredi AA, Bianchi ME, Rovere-Querini P., Trends Immunol. 26(7), 2005
PMID: 15978523
Coregulation of neurite outgrowth and cell survival by amphoterin and S100 proteins through receptor for advanced glycation end products (RAGE) activation.
Huttunen HJ, Kuja-Panula J, Sorci G, Agneletti AL, Donato R, Rauvala H., J. Biol. Chem. 275(51), 2000
PMID: 11007787
Antagonism of RAGE suppresses peripheral nerve regeneration.
Rong LL, Trojaborg W, Qu W, Kostov K, Yan SD, Gooch C, Szabolcs M, Hays AP, Schmidt AM., FASEB J. 18(15), 2004
PMID: 15576484
RAGE modulates peripheral nerve regeneration via recruitment of both inflammatory and axonal outgrowth pathways.
Rong LL, Yan SF, Wendt T, Hans D, Pachydaki S, Bucciarelli LG, Adebayo A, Qu W, Lu Y, Kostov K, Lalla E, Yan SD, Gooch C, Szabolcs M, Trojaborg W, Hays AP, Schmidt AM., FASEB J. 18(15), 2004
PMID: 15576485
Specific expression of an HNK-1 carbohydrate epitope and NCAM on femoral nerve Schwann cells in mice.
Saito H, Nakao Y, Takayama S, Toyama Y, Asou H., Neurosci. Res. 53(3), 2005
PMID: 16171882
Electrical stimulation promotes motoneuron regeneration without increasing its speed or conditioning the neuron.
Brushart TM, Hoffman PN, Royall RM, Murinson BB, Witzel C, Gordon T., J. Neurosci. 22(15), 2002
PMID: 12151542
Pathway sampling by regenerating peripheral axons.
Witzel C, Rohde C, Brushart TM., J. Comp. Neurol. 485(3), 2005
PMID: 15791642

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