Hollen Christopher, Neilson Lee E, Barajas Ramon F, Greenhouse Ian, Spain Rebecca I
Department of Neurology, Veterans Affairs Medical Center, Portland, OR, United States.
Department of Neurology, Oregon Health and Sciences University, Portland, OR, United States.
Front Neurol. 2023 Jan 12;13:1025659. doi: 10.3389/fneur.2022.1025659. eCollection 2022.
While conventional magnetic resonance imaging (MRI) is central to the evaluation of patients with multiple sclerosis, its role in detecting the pathophysiology underlying neurodegeneration is more limited. One of the common outcome measures for progressive multiple sclerosis trials, atrophy on brain MRI, is non-specific and reflects end-stage changes after considerable neurodegeneration has occurred. Identifying biomarkers that identify processes underlying neurodegeneration before it is irreversible and that reflect relevant neurodegenerative pathophysiology is an area of significant need. Accumulating evidence suggests that oxidative stress plays a major role in the pathogenesis of multiple neurodegenerative diseases, including multiple sclerosis. Imaging markers related to inflammation, myelination, and neuronal integrity have been areas of advancement in recent years but oxidative stress has remained an area of unrealized potential. In this article we will begin by reviewing the role of oxidative stress in the pathogenesis of multiple sclerosis. Chronic inflammation appears to be directly related to the increased production of reactive oxygen species and the effects of subsequent oxidative stress appear to be amplified by aging and accumulating disease. We will then discuss techniques in development used in the assessment of MS as well as other models of neurodegenerative disease in which oxidative stress is implicated. Multiple blood and CSF markers of oxidative stress have been evaluated in subjects with MS, but non-invasive imaging offers major upside in that it provides real-time assessment within the brain.
虽然传统的磁共振成像（MRI）是评估多发性硬化症患者的核心手段，但其在检测神经退行性变潜在病理生理学方面的作用较为有限。进行性多发性硬化症试验的常见结局指标之一，即脑部MRI上的萎缩，是非特异性的，反映了在相当程度的神经退行性变发生后的终末期变化。识别在神经退行性变不可逆之前识别其潜在过程并反映相关神经退行性病理生理学的生物标志物是一个迫切需要的领域。越来越多的证据表明，氧化应激在包括多发性硬化症在内的多种神经退行性疾病的发病机制中起主要作用。近年来，与炎症、髓鞘形成和神经元完整性相关的成像标志物取得了进展，但氧化应激仍然是一个尚未实现潜力的领域。在本文中，我们将首先回顾氧化应激在多发性硬化症发病机制中的作用。慢性炎症似乎与活性氧的产生增加直接相关，随后氧化应激的影响似乎因衰老和疾病积累而放大。然后，我们将讨论用于评估MS以及其他涉及氧化应激的神经退行性疾病模型的正在开发的技术。已经在多发性硬化症患者中评估了多种血液和脑脊液氧化应激标志物，但非侵入性成像具有很大优势，因为它可以在脑内提供实时评估。
