Influencing factors and repair advancements in rodent models of peripheral nerve regeneration

Abstract

Peripheral nerve injuries lead to severe functional impairments, with rodent models essential for studying regeneration. This review examines key factors affecting outcomes. Age-related declines, like reduced nerve fiber density and impaired axonal transport of vesicles, hinder recovery. Hormonal differences influence regeneration, with BDNF/trkB critical for testosterone and nerve growth factor for estrogen signaling pathways. Species and strain selection impact outcomes, with C57BL/6 mice and Sprague-Dawley rats exhibiting varying regenerative capacities. Injury models - crush for early regeneration, chronic constriction for neuropathic pain, stretch for traumatic elongation and transection for severe lacerations - provide insights into clinically relevant scenarios. Repair techniques, such as nerve grafts and conduits, show that autografts are the gold standard for gaps over 3 cm, with success influenced by graft type and diameter. Time course analysis highlights crucial early degeneration and regeneration phases within the first month, with functional recovery stabilizing by three to six months. Early intervention optimizes regeneration by reducing scar tissue formation, while later interventions focus on remyelination. Understanding these factors is vital for designing robust preclinical studies and translating research into effective clinical treatments for peripheral nerve injuries.

Keywords: age-related changes; nerve injury models; nerve repair techniques; peripheral nerve regeneration; regenerative medicine; rodent models; sex differences.

Figure 1.

Surgical exposure and direct repair of the sciatic nerve. (A) An incision is made over the postero-lateral aspect of the thigh. The tissue plane between the biceps femoris (*) and gluteus maximus (#) muscles is developed to expose the sciatic nerve (blue chevron). (B) The sciatic nerve is sharply divided. (C) A direct nerve repair is completed using two 10-0 nylon interrupted sutures (enlargement, black arrows).