Transduction of Mechanical stimuli in myelination and peripheral nerve repair

周围神经损伤是外伤（如压迫、分离）引起的常见情况。

Peripheral nerve injuries are common conditions that can arise from trauma (e.g., compression, severance) and can lead to neuropathic pain as well as motor and sensory deficits. Although much knowledge exists on the mechanisms of injury and nerve regeneration, treatments that ensure functional recovery following peripheral nerve injury are limited. Schwann cells, the supporting glial cells in peripheral nerves, orchestrate the regenerative response following nerve injury, by converting to a “repair” phenotype. However, nerve regeneration is often suboptimal in humans as the repair Schwann cells do not sustain their repair phenotype long enough to support the prolonged regeneration times required for successful nerve regrowth. Low intensity pulsed ultrasound (LIPUS) is a nondestructive therapeutic approach which facilitate peripheral nerve regeneration following nerve injury in rodents. Yet, a major gap of knowledge in the current field is how LIPUS is sensed by peripheral nerves. In this application, the objective of this administrative supplement is to provide an outstanding training experience for an underrepresented minority Jenica Acheta. She will aim to determine if the benefit of LIPUS on nerve regeneration is mediated through the repair Schwann cells. We demonstrated that Schwann cells are exquisitely sensitive to alterations in the elasticity of the extracellular matrix (ECM). In addition, because in other tissues and cell types, LIPUS was shown to increase ECM components and to activate ECM-bound receptor responses such as the integrin/FAK/PI3K/AKT pathway, we hypothesize that application of LIPUS modulates repair Schwann cells through the modulation of ECM stiffness and the integrin β1 signaling pathway. Here, our objectives are: (i) to define the effect of LIPUS on peripheral nerve ECM composition, stiffness as well as the ECM receptors expression and activation during regeneration, (ii) to establish that LIPUS promote peripheral nerve repair through modulation of the ECM/integrin β1 signaling pathway. Understanding how LIPUS improves remyelination and peripheral nerve regeneration may necessary underlying mechanisms that clinical efficacy of LIPUS in neuromuscular trauma and neurodegenerative diseases. This reveal the Acheta, providing will help to ensure the administrative supplement will allow the candidate, Jenica to learn new techniques while also increasing the quality of the deliverables on the parent grant by a more detailed analysis of mechanobiology during peripheral nerve regeneration.