NanoBioCel Research Group, Laboratory of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain (I.G., I.V.-B., L.S.-B., G.P., J.L.P); Networking Research Centre of Bioengineering, Biomaterials and Nanomedicine, Institute of Health Carlos III, Madrid, Spain (I.G., I.V.-B., L.S.-B., G.P., J.L.P.); and Bioaraba, NanoBioCel Research Group, Vitoria-Gasteiz, Spain (I.G., I.V.-B., L.S.-B., G.P., J.L.P.).
Pharmacol Rev. 2022 Apr;74(2):439-461. doi: 10.1124/pharmrev.121.000418.
Central nervous system (CNS) diseases, especially acute ischemic events and neurodegenerative disorders, constitute a public health problem with no effective treatments to allow a persistent solution. Failed therapies targeting neuronal recovery have revealed the multifactorial and intricate pathophysiology underlying such CNS disorders as ischemic stroke, Alzheimeŕs disease, amyotrophic lateral sclerosis, vascular Parkisonism, vascular dementia, and aging, in which cerebral microvasculature impairment seems to play a key role. In fact, a reduction in vessel density and cerebral blood flow occurs in these scenarios, contributing to neuronal dysfunction and leading to loss of cognitive function. In this review, we provide an overview of healthy brain microvasculature structure and function in health and the effect of the aforementioned cerebral CNS diseases. We discuss the emerging new therapeutic opportunities, and their delivery approaches, aimed at recovering brain vascularization in this context. SIGNIFICANCE STATEMENT: The lack of effective treatments, mainly focused on neuron recovery, has prompted the search of other therapies to treat cerebral central nervous system diseases. The disruption and degeneration of cerebral microvasculature has been evidenced in neurodegenerative diseases, stroke, and aging, constituting a potential target for restoring vascularization, neuronal functioning, and cognitive capacities by the development of therapeutic pro-angiogenic strategies.
中枢神经系统（CNS）疾病，特别是急性缺血性事件和神经退行性疾病，是一个公共卫生问题，目前尚无有效的治疗方法可以持久解决。针对神经元恢复的失败疗法揭示了缺血性中风、阿尔茨海默病、肌萎缩侧索硬化症、血管性帕金森病、血管性痴呆和衰老等 CNS 疾病背后的多因素和复杂的病理生理学，其中脑微血管损伤似乎起着关键作用。事实上，在这些情况下，血管密度和脑血流减少，导致神经元功能障碍，并导致认知功能丧失。在这篇综述中，我们概述了健康大脑微血管的结构和功能，以及上述大脑中枢神经系统疾病的影响。我们讨论了新兴的治疗机会，以及它们的传递方法，旨在恢复这种情况下的大脑血管化。
缺乏有效的治疗方法，主要集中在神经元恢复上，促使人们寻找其他治疗大脑中枢神经系统疾病的方法。在神经退行性疾病、中风和衰老中，已经证实了脑微血管的破坏和退化，通过开发治疗性血管生成策略来恢复血管化、神经元功能和认知能力，这构成了一个潜在的目标。
