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Molecular Mechanism of the “Babysitter” Procedure for Nerve Regeneration and Muscle Preservation in Peripheral Nerve Repair in a Rat Model

Liu, Hai-Fei MD, PhD*†; Chen, Zeng-Gan MD, PhD; Lineaweaver, William C. MD; Friel, Michael T. MD§; Zhang, Feng MD, PhD†‡

doi: 10.1097/SAP.0000000000000952
Peripheral Nerve Surgery and Research

Objective To investigate the molecular mechanism of nerve “babysitter” for nerve regeneration and muscle preservation in peripheral nerve repair.

Methods Eighty rats were equalized into 4 groups: peroneal nerve transected, group A received no treatment; group B underwent end-to-end repair; group C underwent end-to-side “babysitter” with donor epineurial window; group D underwent end-to-side “babysitter” with 40% donor neurectomy. During second-stage procedure, end-to-end neurorrhaphies were executed in groups A, C, and D. Expression of Insulin-like growth factor (IGF)-1 in spinal cord and IGF-1, TNF-like weak inducer of apoptosis (TWEAK), and Fn14 in anterior tibial muscles were evaluated by histopathology at 4-, 8-, 12-, and 24-week timepoints postoperatively.

Results At 4 weeks, group D expressed comparable IGF-1 with group B, and greater value than groups A and C in spinal cord. By 24 weeks, groups B and D showed higher values than groups A and C. Insulin-like growth factor 1 in muscles were greater in groups C and D than in groups A and B at 4 weeks, and comparable in all groups at 24 weeks. At 4 weeks, immunoreactive scores of TWEAK were 9.00 ± 0, 3.00 ± 0, 6.75 ± 0.75, and 6.75 ± 0.75, respectively. No differences were noticed in all groups by 24 weeks. At 4 weeks, Fn14 were similar in groups A, C, and D, but lower in group B. Group D showed comparable Fn14 with groups B and C, but lower value than group A at 24 weeks.

Conclusions End-to-side nerve “babysitter” in peripheral nerve could promote fiber regeneration and muscle preservation by regulating expression of IGF-1 and TWEAK-Fn14. End-to-side “babysitter” with partial donor neurectomy could achieve comparable effects with end-to-end repair.

From the *Department of Orthopedic Surgery, the Affiliated Hospital of Qingdao University, Shandong; †Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; ‡Joseph M. Still Burn and Reconstructive Center; and §Division of Plastic Surgery, University of Mississippi Medical Center, Jackson, MS.

Received August 8, 2016, and accepted for publication, after revision October 11, 2016.

The first two authors contributed equally to this work and should be considered co-first authors.

Conflicts of interest and sources of funding: none declared.

Reprints: Feng Zhang, MD, PhD, Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Joseph M. Still Burn and Reconstructive Center, Jackson, MS 39216. E-mail:

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