Nerve regeneration in chitosan conduits and in autologous nerve grafts in healthy and in type 2 diabetic Goto-Kakizaki rats.
Knowledge about nerve regeneration after nerve injury and reconstruction in appropriate diabetic animal models is incomplete. Short-term nerve regeneration after reconstruction of a 10-mm sciatic nerve defect with either a hollow chitosan conduit or an autologous nerve graft was investigated in healthy Wistar and diabetic Goto-Kakizaki (GK) rats. After 21 days, axonal outgrowth, the presence of activated and apoptotic Schwann cells and the thickness of the formed matrix in the conduits were measured. In general, nerve regeneration was superior in autologous nerve grafts. In chitosan conduits, a matrix, which was thicker in diabetic rats, was formed and was positively correlated with length of axonal outgrowth. Axonal outgrowth in conduits and in nerve grafts extended further in diabetic rats than in healthy rats. There was a higher percentage of activating transcription factor 3 (ATF3)-immunostained cells in nerve segments from healthy rats than in diabetic rats after autologous nerve graft reconstruction. In chitosan conduits, more cleaved caspase 3-stained Schwann cells were generally observed in the matrix from the diabetic rats than in healthy rats. However, there were fewer apoptotic cells in the distal segment in diabetic rats reconstructed with a chitosan conduit. Preoperative glucose levels were positively correlated with axonal outgrowth after both reconstruction methods. Axonal regeneration was better in autologous nerve grafts than in hollow chitosan conduits and was enhanced in diabetic GK rats compared to healthy rats after reconstruction. This study provides insights into the nerve regeneration process in a clinically relevant diabetic animal model.
Department of Translational Medicine - Hand Surgery, Lund University, Jan Waldenströms gata 5, 205 02, Malmö, Sweden.|Department of Hand Surgery, Skåne University Hospital, Malmö, Sweden.
Lena
L
Stenberg
Department of Orthopaedic Surgery, Integrated Health Sciences, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.
Akira
A
Kodama
Cellectricon AB, Mölndal, Sweden.
Charlotta
C
Lindwall-Blom
Department of Translational Medicine - Hand Surgery, Lund University, Jan Waldenströms gata 5, 205 02, Malmö, Sweden.|Department of Hand Surgery, Skåne University Hospital, Malmö, Sweden.
Lars B
LB
Dahlin
D051700:Activating Transcription Factor 3 / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D048271:Chitosan / Q000737:chemistry; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D005260:Female; D048091:Guided Tissue Regeneration; D009416:Nerve Regeneration; D059348:Peripheral Nerve Injuries / Q000150:complications / Q000503:physiopathology / Q000601:surgery*; D051381:Rats; D017208:Rats, Wistar; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism; D012584:Sciatic Nerve / Q000502:physiology* / Q000637:transplantation; D054457:Tissue Scaffolds / Q000737:chemistry; D014182:Transplantation, Autologous
D051700:Activating Transcription Factor 3; C497108:Atf3 protein, rat; D048271:Chitosan; D053148:Caspase 3
ATF3; Schwann cell; cleaved caspase 3; diabetes; nerve reconstruction