What’s new in nerve?
|Sami Tuffaha, MD
This month, we interview Sami Tuffaha, MD
, senior author of, “Defining the relative impact of muscle versus Schwann cell denervation on functional recovery after delayed nerve repair”, by Karim Sarhane, Benjamin Slavin, Nicholas Hricz, Harsha Malapati, Yi-Nan Guo, Michael Grzelak , Irene Aran Chang, Heather Shappell, Nicholas von Guionneau, Alison Wong, RuifaMi, Ahmet Höke, and Sami Tuffaha. The article was published in the May issue of Experimental Neurology
Defining the relative impact of muscle versus Schwann cell denervation on functional recovery after delayed nerve repair
- What was the motivation for this study?
Beginning in the 1990’s with the seminal works of Tessa Gordon, the importance of chronic Schwann cell denervation as an impediment to nerve regeneration has gained growing attention. Conventional wisdom among clinicians continues to emphasize denervation-induced muscle atrophy as the primary obstacle to achieving satisfactory functional outcomes in the setting of proximal nerve injury and delayed repair. The standard rodent models used to study the effects of chronic denervation simultaneously induce both nerve and muscle denervation prior to nerve repair, making it impossible to isolate and compare the impact of each of these very different processes on functional recovery. We performed this study in the hopes of shedding some light on this critical question.
- What were your key findings?
With 8 weeks of induced nerve or muscle denervation prior to nerve repair, we found that muscle denervation substantially diminished motor functional recovery while nerve/Schwann cell denervation did not have a measurable impact on functional recovery. It is worth noting that in a subsequent study using this model that is yet to be published, we found that isolated nerve denervation for a duration of 16 weeks or greater does impede motor functional recovery.
- What were some of the challenges you faced?
Despite our best efforts to purely isolate nerve and muscle denervation in our model, our muscle denervation group also included a few millimeters of denervated nerve to allow for a nerve-to-nerve coaptation.
- How should the study results be interpreted?
Our findings suggest that the deleterious effects of muscle denervation on functional recovery occur earlier and seem to be more consequential than the effects of Schwann cell denervation. However, it remains unclear how 8-weeks of chronic denervation in a rat translates to humans. It’s also unclear if a greater length of denervated nerve than our model allows would have produced a greater effect in our isolated nerve denervation group.
- What’s next?
We plan to study this question in a non-human primate model to draw conclusions with more direct clinical applicability.