Preconditioning Donor Nerve Using Focused Ultrasound Neurotomy

University of Calgary

Tak-Ho Chu, Nicolas Lasaleta, Siyun Li, Amanda McConnachie, Saud Alzahrani, Laura Curiel, Samuel Pichardo

OBJECTIVE: Experimental evidence suggests that pre-degenerated nerve graft enhances axonal growth compared to freshly harvested nerve graft in nerve 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 nerve tissue using non-invasive focused ultrasound (FUS) and compare the regenerative effects of pre-degenerated nerve grafts to freshly harvested grafts in a rodent sciatic nerve transection and repair model.

METHODS: Adult female Lewis rats received sonication on the right-sided sciatic nerve using a benchtop FUS system at 1.5 MHz, 5 MPa for 10 seconds. Donor animals were kept for 7 days and 1 cm of ipsi- and contralateral nerves were harvested and used for pre-degenerated and freshly harvested grafts, respectively, to bridge a 5mm sciatic nerve gap in recipient rats (n=10 in each group). Behavioral assessments including von Frey sensory test and walking gait were monitored weekly after grafting for 6 weeks. At the end of survival, compound muscle action potential and latency were measured. Gastrocnemius and soleus muscles were weighed. Distal nerves were collected and processed for histology and axon histomorphometry. Additional groups of animals with identical procedures (n=5 in each group) were euthanized at 2 weeks post-grafting to determine early regenerative responses.

RESULTS: FUS 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 metrics were similar between groups except soleus muscle weight was significantly higher in the group with pre-degenerated grafts. As well, similar axon histomorphometric results were found in 2-week survival animals.

CONCLUSIONS: It is possible to induce Wallerian degeneration in distal nerve for grafting using non-invasive FUS. However, we failed to show robust beneficial effects of pre-degenerated grafts compared to freshly harvested grafts in nerve gap repair.