Re-activation of atrophic motor Schwann cells after hypoglossal-facial nerve anastomosis

Facial nerve lesions are common in humans and often require surgical intervention. If repair is delayed, reinnervation can be facilitated by transposing the freshly cut hypoglossal nerve end-to-end directly to the distal facial nerve, allowing for uncompromised hypoglossal axons to reinnervate the denervated facial musculature (hypoglossal-facial anastomosis, HFA). Schwann cells (SCs) in the distal nerve stump have an important function in promoting axonal regeneration by expressing multiple regeneration-associated proteins. Chronically denervated SCs cease to express those factors, but it is unknown whether they can be reactivated by fresh axonal sprouts and regain part of their function. We evaluated SC function and viability in distal facial nerve stump of rats at various time points after chronic denervation as well as following immediate or delayed HFA by assessing their expression of growth-associated protein 43 kDa (GAP-43) and the neuregulin receptors erbB2 and erbB4. Our results show that maximal upregulation of those factors in denervated SCs occurred a few weeks after nerve transection, indicating that a short period of denervation might even be beneficial before nerve repair. Motor SCs denervated for 32 weeks had downregulated their activity and ceased to express the regeneration-associated factors. SCs immediately re-expressed GAP-43, erbB2, and erbB4 following contact with fresh hypoglossal motor axons, demonstrating they are competent to promote regeneration even after long-term denervation.