The Regenerative Potential of Facial Nerve Motoneurons following Chronic Axotomy in Rats

Abstract

Background. The precise mechanisms of nerve regeneration remain unclear. The potential of facial nerve regeneration and probable mechanisms involved following chronic facial nerve injury should be further studied. Methods. Adult male Wistar rats were used to model either (i) facial nerve injury (axotomy) or (ii) reinjury (chronic axotomy followed by a second axotomy within 5 months). The rats were housed in the animal facility of the Eye and ENT Hospital of Shanghai Medical School, Fudan University (Shanghai, China). Expression of Shh (sonic hedgehog) and growth-associated protein 43 (GAP43, a neuronal marker) was detected in bilateral facial nuclei using reverse transcriptase PCR, western blotting analysis, and immunohistochemistry. The number of surviving motoneurons was quantified, and facial nerve regeneration was examined using transmission electron microscopy. Results. Reinjury of the facial nerve 12 weeks after the first axotomy resulted in upregulation of GAP43 mRNA and protein expression in neurons ipsilateral to the axotomy; immunohistochemistry revealed that Shh expression was higher compared with control side facial nuclei at the same time point. GAP43 expression subsequently decreased. Conclusion. The greatest regeneration potential of the facial nerve occurred within 5 months following chronic axotomy in rats, and regeneration may involve the Shh signaling pathway.

Hedging against Neuropathic Pain: Role of Hedgehog Signaling in Pathological Nerve Healing

“…In the reinjured group (chronic axotomy), SHH expression in the reinjured side was higher at 12 weeks compared to the control side, but at the 36 weeks reinjury no differences could be found between injured and control sides. After 36 weeks, SHH expression had decreased even more, suggesting a regeneration potential that peaked within 5 months of initial injury [75]. Unfortunately, lack of rigorous quantification in this study hampered further analyses of SHH expression.…”

“…Finally, several authors recently investigated the effect of chronic axotomy (transection) of the facial nerve in rats (at 12, 20, 28, and 36 weeks post-initial injury), as compared to single axotomy [75]. SHH immunolabeling was observed in motoneurons of the facial nucleus more importantly in the control side that in the injured side (single axotomy).…”

The Role of Sonic Hedgehog Pathway in the Development of the Central Nervous System and Aging-Related Neurodegenerative Diseases

“…During the development of the vertebrate central nervous system, SHH mediates ventral configurable, proliferative, and differentiated capacities of precursor cells (including telencephalon), thereby coordinating size, shape, and cell type ( Ni et al, 2020 ). During the neocortex development, the SHH signaling pathway regulates proliferation of radial glial cells and intermediate precursor cells to maintain the proliferative capacity, differentiation, and survival of neocortex neurons ( Komada, 2012 ).…”