Hayes Genevieve, Pinto Joana, Sparks Sierra N, Wang Congxiyu, Suri Sana, Bulte Daniel P
Department of Engineering Science, Institute of Biomedical Engineering, University of Oxford, Oxford, United Kingdom.
Department of Psychiatry, University of Oxford, Oxford, United Kingdom.
Front Neurosci. 2022 Nov 10;16:1010164. doi: 10.3389/fnins.2022.1010164. eCollection 2022.
Vascular smooth muscle cells (VSMCs) are the key moderators of cerebrovascular dynamics in response to the brain's oxygen and nutrient demands. Crucially, VSMCs may provide a sensitive biomarker for neurodegenerative pathologies where vasculature is compromised. An increasing body of research suggests that VSMCs have remarkable plasticity and their pathophysiology may play a key role in the complex process of neurodegeneration. Furthermore, extrinsic risk factors, including environmental conditions and traumatic events can impact vascular function through changes in VSMC morphology. VSMC dysfunction can be characterised at the molecular level both preclinically, and clinically . However the identification of VSMC dysfunction in living individuals is important to understand changes in vascular function at the onset and progression of neurological disorders such as dementia, Alzheimer's disease, and Parkinson's disease. A promising technique to identify changes in the state of cerebral smooth muscle is cerebrovascular reactivity (CVR) which reflects the intrinsic dynamic response of blood vessels in the brain to vasoactive stimuli in order to modulate regional cerebral blood flow (CBF). In this work, we review the role of VSMCs in the most common neurodegenerative disorders and identify physiological systems that may contribute to VSMC dysfunction. The evidence collected here identifies VSMC dysfunction as a strong candidate for novel therapeutics to combat the development and progression of neurodegeneration, and highlights the need for more research on the role of VSMCs and cerebrovascular dynamics in healthy and diseased states.
血管平滑肌细胞（VSMCs）是脑血管动力学中响应大脑氧气和营养需求的关键调节因子。至关重要的是，对于血管受损的神经退行性病变，VSMCs可能提供一种敏感的生物标志物。越来越多的研究表明，VSMCs具有显著的可塑性，其病理生理学可能在神经退行性变的复杂过程中起关键作用。此外，包括环境条件和创伤事件在内的外在风险因素可通过VSMC形态变化影响血管功能。VSMC功能障碍可在临床前和临床水平进行分子层面的表征。然而，在活体个体中识别VSMC功能障碍对于理解诸如痴呆、阿尔茨海默病和帕金森病等神经疾病发病和进展过程中的血管功能变化至关重要。一种有前景的识别脑平滑肌状态变化的技术是脑血管反应性（CVR），它反映了脑血管对血管活性刺激的内在动态反应，以调节局部脑血流量（CBF）。在这项工作中，我们综述了VSMCs在最常见神经退行性疾病中的作用，并确定了可能导致VSMC功能障碍的生理系统。此处收集的证据表明，VSMC功能障碍是对抗神经退行性变发生和进展的新型治疗方法的有力候选者，并强调需要更多地研究VSMCs和脑血管动力学在健康和疾病状态下的作用。
