title: Mannose-6-phosphate facilitates early peripheral nerve regeneration in thy-1-YFP-H mice.
abstract: The formation of scar tissue following nerve injury has been shown to adversely affect nerve regeneration and evidence suggests that mannose-6-phosphate (M6P), a potential scar reducing agent that affects transforming growth factor (TGF)-β activation, may enhance nerve regeneration. In this study we utilized thy-1-YFP-H mice - a transgenic strain expressing yellow fluorescent protein (YFP) within a subset of axons - to enable visual analysis of axons regenerating through a nerve graft. Using this strain of mouse we have developed analysis techniques to visualize and quantify regeneration of individual axons across the injury site following the application of either M6P or vehicle to the site of nerve injury. No significant differences were found in the proportion of axons regenerating through the graft between M6P- and vehicle-treated grafts at any point along the graft length. Maximal sprouting occurred at 1.0mm from the proximal graft ending in both groups. The maximum change in sprouting levels for both treatment groups occurred between the graft start and 0.5-mm interval for both treatment groups. The difference between repair groups was significant at this point with a greater increase seen in the vehicle group than the M6P group. The average length of axons regenerating across the initial graft entry was significantly shorter in M6P- than in vehicle-treated grafts, indicating that they encountered less impedance. Application of M6P appears to reduce the disruption of regenerating axons and may therefore facilitate quicker recovery; this is likely to result from altered scar tissue formation in M6P grafts in the early stages of recovery. This study also establishes the usefulness of our methods of analysis using the thy-1-YFP-H mouse strain to visualize and quantify regeneration at the level of the individual axon.
authors.affiliation: Unit of Oral and Maxillofacial Medicine and Surgery, School of Clinical Dentistry, University of Sheffield, Claremont Crescent, Sheffield S10 2TA, UK. Electronic address: a.harding@sheffield.ac.uk.
authors.forename: A J
authors.initials: AJ
authors.lastname: Harding
authors.affiliation: Unit of Oral and Maxillofacial Medicine and Surgery, School of Clinical Dentistry, University of Sheffield, Claremont Crescent, Sheffield S10 2TA, UK. Electronic address: c.christmas@sheffield.ac.uk.
authors.forename: C R
authors.initials: CR
authors.lastname: Christmas
authors.affiliation: Renovo Group plc, Core Technology Facility, 48 Grafton Street, Manchester M13 9XX, UK. Electronic address: mark.w.ferguson@manchester.ac.uk.
authors.forename: M W J
authors.initials: MW
authors.lastname: Ferguson
authors.affiliation: Unit of Oral and Maxillofacial Medicine and Surgery, School of Clinical Dentistry, University of Sheffield, Claremont Crescent, Sheffield S10 2TA, UK. Electronic address: a.loescher@sheffield.ac.uk.
authors.forename: A R
authors.initials: AR
authors.lastname: Loescher
authors.affiliation: Unit of Oral and Maxillofacial Medicine and Surgery, School of Clinical Dentistry, University of Sheffield, Claremont Crescent, Sheffield S10 2TA, UK. Electronic address: p.robinson@sheffield.ac.uk.
authors.forename: P P
authors.initials: PP
authors.lastname: Robinson
authors.affiliation: Unit of Oral and Maxillofacial Medicine and Surgery, School of Clinical Dentistry, University of Sheffield, Claremont Crescent, Sheffield S10 2TA, UK. Electronic address: f.boissonade@sheffield.ac.uk.
authors.forename: F M
authors.initials: FM
authors.lastname: Boissonade
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000502:physiology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002921:Cicatrix / Q000188:drug therapy / Q000503:physiopathology; D007091:Image Processing, Computer-Assisted; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008360:Mannosephosphates / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010543:Peroneal Nerve / Q000187:drug effects* / Q000503:physiopathology / Q000601:surgery / Q000637:transplantation
chemical_list: D001426:Bacterial Proteins; D008164:Luminescent Proteins; D008360:Mannosephosphates; D018696:Neuroprotective Agents; C054562:yellow fluorescent protein, Bacteria; C027693:mannose-6-phosphate
keywords: mannose-6-phosphate; nerve regeneration; nerve repair; scarring; thy-1-YFP-H