A meta‐analysis of functional outcomes in rat sciatic nerve injury models

Abstract

Introduction Rat sciatic nerve injury (PNR) is the most utilized model in studies on peripheral nerve regeneration. However, large animal models are increasingly favored based on the assumption that nerve regeneration in rodents achieves more favorable outcomes than in humans. The purpose of this meta‐analysis was to investigate which rat PNR models are more stringent and should be used before utilizing large animal experimentation. Methods A PRISMA‐guided meta‐analysis of the English literature regarding functional outcomes in rat peripheral nerve injury models was conducted. Outcomes of five basic scenarios: (1) transected nerve/negative control, (2) transection with primary microsurgical repair, (3) isogenic/autologous grafts, (4) acellular‐allogenic grafts, and (5) limb transplantation were compared to sciatic nerves without any intervention/positive control. Outcomes were compared using Sciatic Functional Index (SFI). Log‐based projections were generated and evaluated using mean squared error (MSE), one‐way‐ANOVA, and Tukey‐HSD post‐hoc analysis. Results In total, 167 articles met the inclusion criteria. The earliest manifestations of motor recovery were encountered in the transection and primary repair group (p <.0005). There was a significant difference in recovery time and degree of recovery between all surgical models (p <.0005). At 24 weeks, the SFI in hindlimb transplantation group was significantly worse than all other groups (−74.07 ± 2.74, p <.0005). Autografts smaller than 10 mm recovered sooner than autografts longer than 10 mm (p = .021) and autografts recovered faster than allografts. Conclusion This meta‐analysis does not support the belief that neuro‐regeneration is exceptional in transection models. These models remain adequate to provide translatable information and should initially be used in investigational studies.

Implantable Biomaterials for Peripheral Nerve Regeneration–Technology Trends and Translational Tribulations

“… Brenner et al (2008) demonstrated that while the nerve regenerative effect of tacrolimus is significant at 40 days, it is undetectable at 70 days. Similar results are found in a metanalysis by DeLeonibus et al, 2021 .…”

The Grasping Test Revisited: A Systematic Review of Functional Recovery in Rat Models of Median Nerve Injury

“…Best functional outcomes were observable following direct nerve coaptation in end-to-end technique, mirroring results of primary repair of the median nerve in humans [ 40 ]. Like sciatic nerve models, second best outcomes were obtained following autograft repair of segmental nerve injuries [ 1 ].…”

“…Experimental models of peripheral nerve injury are essential to expand our understanding of neural regeneration following therapeutic interventions, which we continuously strive to improve, given the dramatic impact of peripheral nerve injuries on the affected patients’ quality of life [ 1 , 2 , 3 ]. The most frequently used rodent model to study peripheral nerve injury and regeneration is the sciatic nerve of the rat [ 4 , 5 ].…”

“…In regard to the sciatic nerve model of the rat, a comprehensive systematic review published in 2021 has summarized the functional outcome following nerve injury and repair in this commonly used model of peripheral nerve injury [ 1 ]. Several authors have addressed the advantages and disadvantages of the rat sciatic nerve model [ 6 , 25 , 26 ].…”

The effect of a gap concept on peripheral nerve recovery in modified epineurial neurorrhaphy: An experimental study in rats

“…The rate of increase in the deformities in the rats' hind limbs was faster than the restimulation of the muscles by the repaired sciatic nerve. Rat sciatic nerve models are known to be adequate to provide translatable information; however, SFI remains incapable of objectively evaluating functional recovery (DeLeonibus et al, 2021). Navarro reported that the possibilities of evaluating the functional recovery of motor skills after sciatic nerve injury in the awakened animal are rather limited or need considerable efforts to be realized (Navarro, 2016).…”