No abstract

Mechanical allodynia (MA) is the main reason that patients with diabetic peripheral neuropathy (DPN) seek medical advice. It severely debilitates the quality of life. Investigating hyperglycemia-induced changes in neural transcription could provide fundamental insights into the complex pathogenesis of painful DPN (PDPN). Gene expression profiles of physiological dorsal root ganglia (DRG) have been studied. However, the transcriptomic changes in DRG neurons in PDPN remain largely unexplored. In this study, by single-cell RNA sequencing on dissociated rat DRG, we identified five physiological neuron types and a novel neuron type MAAC (Fxyd7+/Atp1b1+) in PDPN. The novel neuron type originated from peptidergic neuron cluster and was characterized by highly expressing genes related to neurofilament and cytoskeleton. Based on the inferred gene regulatory networks, we found that activated transcription factors Hobx7 and Larp1 in MAAC could enhance Atp1b1 expression. Moreover, we constructed the cellular communication network of MAAC and revealed its receptor-ligand pairs for transmitting signals with other cells. Our molecular investigation at single-cell resolution advances the understanding of the dynamic peripheral neuron changes and underlying molecular mechanisms during the development of PDPN.

It is critical to repair severed facial nerves, as lack of treatment may cause long‐term motor and sensory impairments. Ciliary neurotrophic factor (CNTF) plays an important role in terms of enhancing nerve axon regrowth and maturation during peripheral nerve regeneration after injury. However, simple application of CNTF to the transected nerve site does not afford functional recovery, because it is rapidly flushed away by bodily fluids. The aim of the present study was the construction of a new, bioactive composite nerve graft facilitating persistent CNTF delivery to aid the reconstruction of facial nerve defects. The in vitro study showed that the bioactive nerve graft generated sustainable CNTF release for more than 25 days. The bioactive nerve graft was then transplanted into the injury sites of rat facial nerves. At 6 and 12 weeks post‐transplantation, functional and histological analyses showed that the bioactive nerve graft featuring immobilized CNTF significantly enhanced nerve regeneration in terms of both axonal outgrowth and Schwann cell proliferation in the rat facial nerve gap model, compared to a collagen tube with adsorbed CNTF that initially released high levels of CNTF. The bioactive nerve graft may serve as novel, controlled bioactive release therapy for facial nerve regeneration.