Transduction of Mechanical stimuli in myelination and peripheral nerve repair

周围神经损伤是由创伤(如压迫、切断)引起的常见情况 并可能导致神经病理性疼痛以及运动和感觉障碍。尽管有很多知识存在于 损伤和神经再生的机制，确保功能恢复的治疗 周围神经损伤有限。雪旺细胞，周围神经中的支持神经胶质细胞，协调 神经损伤后的再生反应，转化为“修复”表型。然而，神经 在人类中，再生通常是次优的，因为修复的雪旺细胞不能维持其修复表型 足够长的时间来支持成功的神经再生所需的延长的再生时间。 低强度脉冲超声(LIPUS)是一种非破坏性的治疗方法，有助于 啮齿动物神经损伤后的周围神经再生。然而，当前知识的一个主要差距是 菲尔德是LIPUS被周围神经感知的方式。在此应用程序中，此管理程序的目标是 补充是为代表不足的少数民族Jenica Acheta提供出色的培训经验。 她将致力于确定LIPUS对神经再生的益处是否通过修复而调节 雪旺细胞。我们证明了雪旺细胞对血管弹性的改变非常敏感。 细胞外基质(ECM)。此外，由于在其他组织和细胞类型中，LIPUS被显示为 增加细胞外基质成分，激活细胞外基质结合受体反应，如整合素/FAK/PI3K/AKT 途径，我们假设LIPUS的应用通过调节 细胞外基质刚性与整合素β-1信号通路。在这里，我们的目标是：(I)界定LIPUS的影响 外周神经细胞外基质的组成、僵硬及其受体的表达和激活 再生，(Ii)确定LIPUS通过调节 细胞外基质/整合素β-1信号通路。 了解LIPUS如何促进髓鞘再生和周围神经再生可能 LIPUS治疗神经肌肉病临床疗效的必要机制 创伤和神经退行性疾病。这 揭示 这个 阿切塔 提供 将有助于确保 行政副刊将允许候选人杰尼卡 在学习新技术的同时，通过以下方式提高母基金交付成果的质量 更详细地分析周围神经再生过程中的机械生物学。

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.