Peripheral Nerve Rehabilitation

Peripheral nerve rehabilitation involves medical, physical, and biological strategies aimed at restoring function after damage to the peripheral nervous system (PNS).

• 🧠 Restore nerve conduction and function
• 💪 Prevent muscular atrophy and joint stiffness
• 🔄 Promote axonal regeneration and remyelination
• 🛑 Alleviate neuropathic pain

• Natural axonal regrowth (1–3 mm/day)
• Activation of Schwann cells for guidance and myelin repair
• Involvement of molecular mediators like AQP3, NGF, BDNF

• Physical therapy – ROM exercises, electrical stimulation, sensory re-education
• Pharmacotherapy – Pain control, neuroprotective agents
• Surgical repair – Nerve grafting, transfers, decompression
• Experimental approaches – Stem cells, biomaterials, gene therapy

Delayed recovery may occur in conditions with:

• Diabetes mellitus
• Severe trauma or prolonged compression
• Molecular deficiencies (e.g., AQP3-deficiency per recent mouse model studies)

• AQP3 and nerve repair – Experimental study
• Peripheral nerve injury: A review

Wang et al and the neurosurgeon Miao Li from the China-Japan Union Hospital of Jilin University in a experimental research study investigated the possible functions of AQP3 in peripheral nerve rehabilitation based on AQP3-deficient mice.

Mature 8-week-old female AQP3-deficient (AQP3-/-) mice and C57BL/6 mice initially weighing 25~30 g were used in this study. Schwann cells were isolated from sciatic nerves of WT and AQP3-/- mice, respectively. AQP3 mRNA and protein expression in sciatic nerve tissues and Schwann cells were detected by RT-PCR, immunoblot analysis, and immunofluorescence staining. Sciatic nerve cross sections from the WT and AQP3-/- mice were stained by a toluidine-blue agent to identify the potential influence of AQP3 deficiency on the morphology of nerve fibers. The proliferation and migration ability of AQP3-/- and WT Schwann cells were observed in primary cell cultures. To explore the possible role of AQP3 in nerve repair processes, sciatic nerve contusion models were established, and walking track analysis was performed on both WT and AQP3-/- mice.

AQP3 was localized in the membrane of Schwann cells. AQP3 deficiency did not alter the morphology of fibers in the sciatic nerve. There was an increase in AQP3 protein expression in the sciatic nerve of wild-type mice after injury. Primary culture of Schwann cells and in vitro wound healing model revealed that AQP3-deficient Schwann cells exhibited the same morphology, while showing lower proliferation and migration ability compared with wild-type Schwann cells. There was an obvious delay in motor function rehabilitation in AQP3-deficient mice compared with that of wild-type mice.

The study suggested that AQP3 is localized in the membrane of Schwann cells and facilitates Schwann cells' proliferation and migration. AQP3 deficiency impaired nerve rehabilitation in the wound healing model, both in vitro and in vivo. The study supports the hypothesis that AQP3 participates in myelin damage and repair, and the mechanisms underlying AQP3 in the field of myelin repair and regeneration in peripheral nerves deserve further investigation and exploration in detail ¹⁾

This preclinical study investigates the role of Aquaporin-3 (AQP3) in peripheral nerve regeneration using AQP3-deficient (AQP3⁻/⁻) and wild-type (WT) mice in a sciatic nerve contusion model. The authors analyze Schwann cell behavior and functional recovery to assess how AQP3 deficiency influences nerve healing.

• Clear Hypothesis: Explores a novel role of AQP3 in nerve repair.
• Robust Design: Combines _in vivo_ and _in vitro_ experiments with molecular and functional techniques (RT-PCR, immunostaining, walking track).
• Biological Significance: Shows that AQP3 is involved in Schwann cell migration and regeneration.

• Lack of Mechanistic Insight: No exploration of molecular pathways affected by AQP3.
• Narrow Model: Only contusion injuries studied; no comparison with other injury types (e.g., crush, transection).
• Sex Bias: Only female mice were used.
• Limited Functional Testing: No electrophysiology to confirm functional deficits.
• Translational Gap: No data supporting the potential for clinical translation or pharmacological modulation of AQP3.

This study provides promising evidence that AQP3 facilitates Schwann cell function and nerve regeneration. It opens new research lines in molecular neurorehabilitation but lacks mechanistic depth and broader model validation. Future research should explore:

• AQP3-regulated signaling pathways
• Sex and age variation
• Additional functional readouts
• Pharmacological manipulation of AQP3