Predegenerating donor nerve for grafting using focused ultrasound neurotomy

Abstract Early experimental evidence suggests that predegenerated nerve graft enhance axonal growth compared to freshly harvested nerve graft in nerve gap repair. However, the practicality of surgically pre-conditioning nerves for grafting remains a major obstacle. Herein, we aim to investigate the...

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Main Authors: Tak-Ho Chu, Nicolas Lasaleta, Siyun Li, Amanda McConnachie, Leonardo Molina, Saud Alzahrani, Laura Curiel, Samuel Pichardo, Rajiv Midha
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-00316-8
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author Tak-Ho Chu
Nicolas Lasaleta
Siyun Li
Amanda McConnachie
Leonardo Molina
Saud Alzahrani
Laura Curiel
Samuel Pichardo
Rajiv Midha
author_facet Tak-Ho Chu
Nicolas Lasaleta
Siyun Li
Amanda McConnachie
Leonardo Molina
Saud Alzahrani
Laura Curiel
Samuel Pichardo
Rajiv Midha
author_sort Tak-Ho Chu
collection DOAJ
description Abstract Early experimental evidence suggests that predegenerated nerve graft enhance axonal growth compared to freshly harvested nerve graft in nerve gap repair. However, the practicality of surgically pre-conditioning nerves for grafting remains a major obstacle. Herein, we aim to investigate the feasibility of focal lesioning of nerve tissue using high-intensity focused ultrasound (HIFU) and compare the regenerative effects of predegenerated nerve grafts to freshly harvested grafts in a rat sciatic nerve transection and repair model. As a proof of principle, sciatic nerves were exposed for HIFU lesioning to increase targeting accuracy. HIFU induced focal thermal lesioning to the sciatic nerve, resulting in p75 and cJun up-regulation at the distal segment observed at 7 days post-sonication. All behavioural outcome metrics including von Frey sensory test and walking gait were similar between animals with freshly harvested and predegenerated nerve grafts except soleus muscle weight was significantly higher in the latter group. As well, similar axon histomorphometric results were found in 2-week survival animals. Our findings showed that it is possible to induce Wallerian degeneration in distal nerve for grafting using non-invasive HIFU. However, limited beneficial effects of predegenerated grafts were obtained compared to freshly harvested grafts in nerve gap repair.
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spelling doaj-art-b1f23b57a3f8440486481908a2fc69562025-08-20T03:52:23ZengNature PortfolioScientific Reports2045-23222025-05-0115111110.1038/s41598-025-00316-8Predegenerating donor nerve for grafting using focused ultrasound neurotomyTak-Ho Chu0Nicolas Lasaleta1Siyun Li2Amanda McConnachie3Leonardo Molina4Saud Alzahrani5Laura Curiel6Samuel Pichardo7Rajiv Midha8Department of Clinical Neurosciences, University of CalgaryDepartment of Clinical Neurosciences, University of CalgaryDepartment of Radiology, Cumming School of Medicine, University of CalgaryDepartment of Clinical Neurosciences, University of CalgaryCSM optogenetics, Cumming School of Medicine, University of CalgaryDepartment of Clinical Neurosciences, University of CalgaryHotchkiss Brain Institute, University of CalgaryDepartment of Clinical Neurosciences, University of CalgaryDepartment of Clinical Neurosciences, University of CalgaryAbstract Early experimental evidence suggests that predegenerated nerve graft enhance axonal growth compared to freshly harvested nerve graft in nerve gap repair. However, the practicality of surgically pre-conditioning nerves for grafting remains a major obstacle. Herein, we aim to investigate the feasibility of focal lesioning of nerve tissue using high-intensity focused ultrasound (HIFU) and compare the regenerative effects of predegenerated nerve grafts to freshly harvested grafts in a rat sciatic nerve transection and repair model. As a proof of principle, sciatic nerves were exposed for HIFU lesioning to increase targeting accuracy. HIFU induced focal thermal lesioning to the sciatic nerve, resulting in p75 and cJun up-regulation at the distal segment observed at 7 days post-sonication. All behavioural outcome metrics including von Frey sensory test and walking gait were similar between animals with freshly harvested and predegenerated nerve grafts except soleus muscle weight was significantly higher in the latter group. As well, similar axon histomorphometric results were found in 2-week survival animals. Our findings showed that it is possible to induce Wallerian degeneration in distal nerve for grafting using non-invasive HIFU. However, limited beneficial effects of predegenerated grafts were obtained compared to freshly harvested grafts in nerve gap repair.https://doi.org/10.1038/s41598-025-00316-8HIFUAutograftPredegenerationMachine learningBehavioural studies
spellingShingle Tak-Ho Chu
Nicolas Lasaleta
Siyun Li
Amanda McConnachie
Leonardo Molina
Saud Alzahrani
Laura Curiel
Samuel Pichardo
Rajiv Midha
Predegenerating donor nerve for grafting using focused ultrasound neurotomy
Scientific Reports
HIFU
Autograft
Predegeneration
Machine learning
Behavioural studies
title Predegenerating donor nerve for grafting using focused ultrasound neurotomy
title_full Predegenerating donor nerve for grafting using focused ultrasound neurotomy
title_fullStr Predegenerating donor nerve for grafting using focused ultrasound neurotomy
title_full_unstemmed Predegenerating donor nerve for grafting using focused ultrasound neurotomy
title_short Predegenerating donor nerve for grafting using focused ultrasound neurotomy
title_sort predegenerating donor nerve for grafting using focused ultrasound neurotomy
topic HIFU
Autograft
Predegeneration
Machine learning
Behavioural studies
url https://doi.org/10.1038/s41598-025-00316-8
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