Peripheral Nerve Regeneration

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When a nerve is lacerated, the axon segments distal to the injury site deteriorate and recede in a process called Wallerian degeneration.  Changes in gene expression in the neuronal cell bodies support axonal elongation from the site of injury.  Schwann cells convert from a maintenance state to a repair state to support axonal regeneration.  The production of myelination proteins is halted and trophic factors are released to stimulate axonal elongation.  There is also evidence that signals released from denervated muscle play a role in axonal regeneration.  

As a hand surgeon who treats traumatic peripheral nerve injuries frequently, Dr. Weber is interested in better understanding the process of peripheral nerve regeneration, in the hopes of bringing new therapeutics to clinical use.  Even though surgical repair of a lacerated nerve is a simple technique, most patients are left with some degree of functional deficit, ranging from mild decreases in sensation to severe motor weakness.

Areas of interest include:

1.  Muscle-nerve signaling following nerve injury

2.  Premature repair Schwann cell deterioration 

3.  Differences between human and rodent peripheral nerve regeneration

Preferential motor reinnervation (PMR) is the preference of regenerating motor axons to reconnect with muscle rather than skin, which is a wasted connection that does not produce any effect.  

Crush injury to the distal nerve near the neuromuscular junction abolishes PMR, indicating the presence of a muscle-derived signal which improves axonal regeneration.

Exosomes are small membrane-encapsulated vesicles which carry proteins, DNA, and multiple types of RNA between cells for communication.  Exosomes are reciprocally released between muscle and nerve at a normal neuromuscular junction and are also found between muscle fibers adjacent to muscle stem cells.  Exosomes released from denervated muscle can rescue PMR after crush injury.  We are interested in identifying the signals carried by muscle-derived exosomes which can improve nerve regeneration and PMR.  

Over the course of the peripheral nerve regeneration process, the repair Schwann cell deteriorates into a chronically denervated Schwann cell, which is neither an effective repair cell nor myelinating cell.  In rodents, this occurs about 1 month after injury.  But, by that time, the majority of the regenerating axons have reached the target muscle/skin.  In humans, this deterioration occurs around 3 months post-injury.  However, in humans, nerves must regenerate over much longer distances, sometimes requiring 6-12 months to reach target destinations.  The loss of the repair Schwann cell may be one reason that human peripheral nerve regeneration fares worse than equivalent injuries in rodents.  Our lab is interested in better elucidating this process of Schwann cell degeneration and determining ways to reverse or prevent the deterioration.