Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.
Department of Neurology, Neuromuscular Division, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Adv Biol (Weinh). 2024 May;8(5):e2400020. doi: 10.1002/adbi.202400020. Epub 2024 Mar 28.
Understanding the intricate processes of neuronal growth, degeneration, and neurotoxicity is paramount for unraveling nervous system function and holds significant promise in improving patient outcomes, especially in the context of chemotherapy-induced peripheral neuropathy (CIPN). These processes are influenced by a broad range of entwined events facilitated by chemical, electrical, and mechanical signals. The progress of each process is inherently linked to phenotypic changes in cells. Currently, the primary means of demonstrating morphological changes rely on measurements of neurite outgrowth and axon length. However, conventional techniques for monitoring these processes often require extensive preparation to enable manual or semi-automated measurements. Here, a label-free and non-invasive approach is employed for monitoring neuronal differentiation and degeneration using quantitative phase imaging (QPI). Operating on unlabeled specimens and offering little to no phototoxicity and photobleaching, QPI delivers quantitative maps of optical path length delays that provide an objective measure of cellular morphology and dynamics. This approach enables the visualization and quantification of axon length and other physical properties of dorsal root ganglion (DRG) neuronal cells, allowing greater understanding of neuronal responses to stimuli simulating CIPN conditions. This research paves new avenues for the development of more effective strategies in the clinical management of neurotoxicity.
理解神经元生长、退化和神经毒性的复杂过程对于揭示神经系统功能至关重要,并有望改善患者的预后,特别是在化疗诱导的周围神经病(CIPN)方面。这些过程受到化学、电和机械信号促进的广泛交织事件的影响。每个过程的进展都与细胞的表型变化内在相关。目前,主要的形态变化检测手段依赖于神经突生长和轴突长度的测量。然而,传统的监测这些过程的技术通常需要广泛的准备工作,以实现手动或半自动测量。在这里,使用无标记和非侵入性的方法,利用定量相位成像(QPI)来监测神经元的分化和退化。该方法对未标记的样本进行操作,几乎没有光毒性和光漂白,提供了光学路径长度延迟的定量图谱,客观地测量了细胞形态和动力学。这种方法能够可视化和量化背根神经节(DRG)神经元细胞的轴突长度和其他物理特性,有助于更好地理解神经元对模拟 CIPN 条件的刺激的反应。这项研究为开发更有效的神经毒性临床管理策略开辟了新的途径。