Regenerative failure of diabetic nerves bridging transection injuries.
BACKGROUND
Failed regeneration compounds the deficits imposed by diabetes from peripheral neuropathy. In this work, we addressed how diabetes or local glucose toxicity might impact peripheral nerve trunk regeneration and reconstitution across major sciatic nerve transection injuries of rats.


METHODS
Specific conduits, amendable to manipulation of infused glucose concentrations through a T connection, were perfused with 5 or 30 mmol/L glucose in nondiabetics or 5 mmol/L glucose in rats with experimental diabetes. Quantitative early and later regenerative outgrowth was measured.


RESULTS
Local glucose exposure had no impact on early axon or Schwann cell outgrowth or partnering nor later myelinated axon regeneration. Despite only mildly attenuated early sprouting of axons with Schwann cells, diabetic bridges exhibited massive later failure of reconstitution by 3 weeks after injury.


CONCLUSIONS
Diabetes is associated with severe limitations in regenerative success, despite appropriate early axon outgrowth.
Zochodne
Douglas W
DW
University of Calgary, Department of Clinical Neurosciences, Hotchkiss Brain Institute, Canada. dzochodn@ucalgary.ca
Guo
Gui Fang
GF
Magnowski
Brooks
B
Bangash
Mohammed
M
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D009186:Myelin Sheath / Q000473:pathology; D009416:Nerve Regeneration / Q000187:drug effects; D016900:Neurofilament Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000378:metabolism / Q000473:pathology; D012584:Sciatic Nerve / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors; D014950:Wounds, Penetrating / Q000473:pathology / Q000503:physiopathology*
D005904:Glial Fibrillary Acidic Protein; D016900:Neurofilament Proteins; D005947:Glucose