Transduction of Mechanical stimuli in myelination and peripheral nerve repair

髓鞘形成和周围神经修复中机械刺激的转导

• 批准号: 10571229
• 负责人: Yannick Poitelon
• 金额: $ 3.41万
• 依托单位: ALBANY MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10571229
• 关键词: Administrative Supplement; Disease; ECM receptor; Elasticity; Ensure; Extracellular Matrix; Human; Injury; Integrins; Knowledge; Lead; Learning; Mediating; Modeling; Motor; Myelin; Natural regeneration; Nerve; Nerve Regeneration; Neurodegenerative Disorders; Neuroglia; PI3K/AKT; PTK2 gene; Pathway interactions; Peripheral; Peripheral Nerves; Peripheral nerve injury; Phenotype; Physiologic pulse; Receptor Activation; Recovery of Function; Regenerative response; Rodent; Schwann Cells; Sensory; Signal Pathway; Techniques; Therapeutic; Time; Tissues; Training; Trauma; Underrepresented Minority; cell type; clinical efficacy; experience; improved; mechanical stimulus; myelination; nerve injury; neuromuscular; new therapeutic target; painful neuropathy; parent grant; peripheral nerve regeneration; peripheral nerve repair; receptor binding; receptor expression; remyelination; repaired; response; ultrasound

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.

周围神经损伤是可由创伤引起的常见病症（例如，压缩，切断） 并可导致神经性疼痛以及运动和感觉缺陷。虽然很多知识存在于 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。雪旺细胞是周围神经的支持神经胶质细胞， 神经损伤后的再生反应，通过转化为“修复”表型。然而，神经 由于修复性雪旺细胞不能维持其修复表型， 长到足以支持成功神经再生所需的延长的再生时间。 低强度脉冲超声（LIPUS）是一种无损治疗方法， 啮齿类动物神经损伤后的周围神经再生。然而，目前的一个主要知识缺口是， 场是LIPUS如何被周围神经感知。在本申请中，该行政管理的目的是 补充是为代表性不足的少数民族Jenica Acheta提供出色的培训经验。 她的目标是确定LIPUS对神经再生的益处是否是通过修复介导的。 雪旺氏细胞。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显示出 增加ECM成分并激活ECM结合的受体应答，如整合素/FAK/PI 3 K/AKT 通路，我们假设LIPUS的应用通过调节 ECM硬度和整合素β1信号通路。在这里，我们的目标是：（i）定义LIPUS的效果 对周围神经细胞外基质成分、硬度以及细胞外基质受体表达和激活的影响 再生，（ii）建立LIPUS通过调节周围神经再生促进周围神经修复， ECM/整合素β1信号通路。 了解LIPUS如何改善髓鞘再生和周围神经再生， LIPUS在神经肌肉疾病中的临床疗效的必要潜在机制 创伤和神经退行性疾病。这 揭示 的 阿切塔 提供 将有助于确保 行政补助金将允许候选人杰妮卡 学习新技术，同时提高父母补助金的交付物质量， 周围神经再生过程中机械生物学的更详细分析。