Kimura Shintaro, Iwata Maho, Takase Hajime, Lo Eng H, Arai Ken
Neuroprotection Research Laboratories, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Life Science Research Center, Gifu University, Gifu, Japan.
J Cereb Blood Flow Metab. 2025 Mar;45(3):381-395. doi: 10.1177/0271678X241305899. Epub 2024 Dec 12.
Chronic cerebral hypoperfusion (CCH) is an important clinical condition characterized by a prolonged reduction in cerebral blood flow that contributes to several neurodegenerative diseases, including vascular dementia and Alzheimer's disease. A number of rodent models of CCH have been developed that mimic the human pathological conditions of reduced cerebral perfusion. These models have been instrumental in elucidating the molecular and cellular mechanisms involved in CCH-induced brain damage. Oxidative stress is induced by perturbations in cellular pathways caused by CCH, including mitochondrial dysfunction, ion pump dysfunction, and adenosine triphosphate (ATP) depletion. The deleterious stress leads to the accumulation of reactive oxygen species (ROS) and exacerbates damage to neuronal structures, significantly impairing cognitive function. Among the various therapeutic strategies being evaluated, edaravone, a potent antioxidant, is emerging as a promising drug due to its neuroprotective properties against oxidative stress. Initially approved for use in ischemic stroke, research using rodent CCH models has shown that edaravone has significant efficacy in scavenging free radicals and ameliorating oxidative stress-induced neuronal damage under CCH conditions. This mini-review summarizes the current literature on the rodent models of CCH and then discusses the therapeutic potential of edaravone to reduce neuronal and vascular damage caused by CCH-induced oxidative stress.
慢性脑灌注不足（CCH）是一种重要的临床病症，其特征是脑血流量长期减少，可导致多种神经退行性疾病，包括血管性痴呆和阿尔茨海默病。已经开发了许多CCH啮齿动物模型，这些模型模拟了脑灌注减少的人类病理状况。这些模型有助于阐明CCH诱导的脑损伤所涉及的分子和细胞机制。氧化应激是由CCH引起的细胞途径扰动诱导的，包括线粒体功能障碍、离子泵功能障碍和三磷酸腺苷（ATP）耗竭。这种有害应激导致活性氧（ROS）积累，并加剧对神经元结构的损伤，显著损害认知功能。在正在评估的各种治疗策略中，依达拉奉作为一种有效的抗氧化剂，由于其对氧化应激的神经保护特性，正成为一种有前景的药物。依达拉奉最初被批准用于缺血性中风，使用啮齿动物CCH模型的研究表明，依达拉奉在清除自由基和改善CCH条件下氧化应激诱导的神经元损伤方面具有显著疗效。这篇综述总结了当前关于CCH啮齿动物模型的文献，然后讨论了依达拉奉减少CCH诱导的氧化应激所导致的神经元和血管损伤的治疗潜力。
