Effect of Axonal Trauma on Nerve Regeneration in Side-to-side Neurorrhaphy: An Experimental Study

Abstract

Background:Side-to-side (STS) neurorrhaphy can be performed distally to ensure timely end-organ innervation. It leaves the distal end of the injured nerve intact for further reconstruction. Despite encouraging clinical results, only few experimental studies have been published to enhance the regeneration results of the procedure. We examined the influence of different size epineural windows and degree of axonal injury of STS repair on nerve regeneration and donor nerve morbidity.Methods:Three clinically relevant repair techniques of the transected common peroneal nerve (CPN) were compared. Group A: 10-mm long epineural STS windows; group B: 2-mm long windows and partial axotomy to the donor tibial nerve; and group C: 2-mm long windows with axotomies to both nerves. Regeneration was followed by the walk track analysis, nerve morphometry, histology, and wet muscle mass calculations.Results:The results of the walk track analysis were significantly better in groups B and C compared with group A. The nerve fiber count, total fiber area, fiber density, and percentage of the fiber area values of CPN of the group C were significantly higher when compared with group A. The wet mass ratio of the CPN-innervated anterior tibial muscle was significantly higher in group C compared with group A. The wet mass ratio of the tibial nerve–innervated gastrocnemial muscle was higher in group A compared with the other groups.Conclusions:All three variations of the STS repair technique showed nerve regeneration. Deliberate donor nerve axotomy enhanced nerve regeneration. A larger epineural window did not compensate the effect of axonal trauma on nerve regeneration.

Molecular Basis of Surgical Coaptation Techniques in Peripheral Nerve Injuries

“…This method has been used both in isolation and in conjunction with the other repair techniques of ETE and ETS ( Figure 7 ). There has been a combination of multiple animal studies and a smattering of human studies, published on this relatively new method [ 55 , 56 , 57 , 58 , 59 ]. In 1999, Yuksel et al performed side-to-side nerve coaptation procedures between the peroneal and tibial nerve trunks of ten rats and demonstrated that axonal passage was possible with side-to-side nerve neurorrhaphy.…”

“…One possible explanation has been proposed by Napoli et al, who developed a mouse model in which the activation of the Ras-MAP signaling pathway was sufficient to initiate SC dedifferentiation without axonal injury [ 56 ]. In this pathway, Ras activates the proto-oncogene serine threonine protein kinase Raf, which then activates mitogen-activated protein kinase-kinase (MEK), in turn promoting the mitogen-activated protein kinase (ERK) signaling that maintains the dedifferentiated state of SCs ( Figure 8 ) [ 58 , 59 , 60 ].…”

“…Shea et al demonstrated that a side-to-side bridge consisting of a collagen based nerve conduit coupled with an ETE repair of the proximally transected nerve resulted in less muscle atrophy and fewer signs of muscle denervation, such as pyknotic nuclei and smaller muscle fibers, than ETE repair or STS bridge alone [ 54 ]. The authors explained that a benefit of using a bridge is to obviate the extensive nerve dissection required to mobilize the nerves to create a direct STS connection thus avoiding inadvertent injury to the nerves during dissection [ 58 ]. The molecular mechanism of STS bridges was investigated by Gordon et al, who found that they help sustain the donor segment by releasing growth-supporting factors such as cAMP and neuregulin from the donor nerve [ 60 ].…”

Low-Level Laser Therapy (LLLT) Improves the Repair Process of Peripheral Nerve Injuries: A Mini Review

“…In the search to repair such lesions, the end-to-side neurorrhaphy technique was described in the literature as an alternative when it is impractical to apply direct grafts [7,8]. The sural nerve can be used as a donor of fibers and applied in the end-to-side neurorrhaphy technique, since its morphology and growth in symmetry would be a suitable model for experimental studies in neuropathies [9].…”