Neurovascular unit in ischemic stroke in older adults: a narrative review

Wang, Chengyuan1; Yang, Yi1; Xiong, Tianqing1,2,3,*; Li, Shun3,*

1Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China

2Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Yangzhou University, Yangzhou, Jiangsu Province, China

3Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

*Correspondence to: Tianqing Xiong, PhD, 007418@yzu.edu.cn; Shun Li, MD, lis24@upmc.edu.

Abstract

There is a significant global death and disability rate associated with ischemic stroke, making it one of the most prevalent disorders. With the increasing worldwide aging population, the prevalence of ischemic stroke has notably increased and has emerged as a pivotal issue in public health. The neurovascular unit primarily consists of neurons, astrocytes, microglia, and brain microvascular endothelial cells. These cells are structurally tightly connected; together, they maintain the balance of brain function and are crucial for brain function and cerebral ischemic damage. Emerging studies in recent years have demonstrated the development of associations between ischemic stroke and the vascular neural units. The neurovascular unit characterizes the whole-tissue response to stroke, encompassing the interrelationship and reciprocal impact of neurons, glial cells, and microvessels. The neurovascular unit results in compromised integrity of the microvasculature and blood–brain barrier, neuronal cell death, the glial response, the inflammatory response, and immune cell infiltration, all of which are strongly associated with the course of ischemic stroke. This narrative review explores the complex relationship between ischemic stroke and the neurovascular unit in the context of an aging population. With aging, the neurovascular unit undergoes structural and functional changes that predispose the elderly to higher risks of stroke and complicate recovery post-stroke. We explore the impact of aging on the neurovascular unit, focusing on how age-related alterations in the neurovascular unit contribute to the susceptibility to ischemic stroke and influence the repair mechanisms post-stroke. The review highlights the compromised integrity of the microvascular and blood-brain barriers, increased neuronal cell death, heightened glial response, inflammatory reactions, and immune cell infiltration associated with aging, all of which are critical in the progression of ischemic stroke. By examining the latest research, we aim to provide a comprehensive understanding of the neurovascular unit’s role in ischemic stroke within the aging population and discuss how regenerative medicine offers novel strategies for treatment, emphasizing neuroprotection, neuroregeneration, and neurorepair. These aspects are of paramount importance for clinical interventions tailored to the elderly, who often present with unique challenges in stroke management. The review underscores the importance of considering the aging factor in stroke research and treatment, as the cellular interactions within the neurovascular unit form a complex system that is significantly influenced by the aging process. These connections cannot be overlooked in the quest for effective stroke therapies. The development of regenerative medicine presents new perspectives on stroke treatment, particularly for the elderly, where traditional therapies may be less effective or carry higher risks. This narrative review aims to bridge the gap in knowledge regarding the neurovascular unit’s role in ischemic stroke within the context of aging, providing a foundation for the development of targeted therapies that can improve outcomes for this vulnerable population.

老年人缺血性脑卒中的神经血管单元： 叙述性综述

摘要

缺血性中风在全球的致死率和致残率都很高，是发病率最高的疾病之一。随着全球老龄化人口的不断增加，缺血性中风的发病率也明显上升，并已成为公共卫生领域的一个关键问题。神经血管单元主要由神经元、星形胶质细胞、小胶质细胞和脑微血管内皮细胞组成。这些细胞在结构上紧密相连，共同维持着大脑功能的平衡，对大脑功能和脑缺血损伤至关重要。近年来的新研究表明，缺血性中风与血管神经单元之间存在关联。神经血管单元是脑卒中全组织反应的特征，包括神经元、神经胶质细胞和微血管的相互关系和相互影响。神经血管单元导致微血管和血脑屏障完整性受损、神经元细胞死亡、神经胶质细胞反应、炎症反应和免疫细胞浸润，所有这些都与缺血性中风的病程密切相关。本综述以人口老龄化为背景，探讨缺血性中风与神经血管单元之间的复杂关系。随着年龄的增长，神经血管单元会发生结构和功能上的变化，这些变化使老年人发生卒中的风险增加，并使卒中后的恢复复杂化。我们探讨了衰老对神经血管单元的影响，重点是神经血管单元与年龄相关的改变如何导致缺血性中风的易感性并影响中风后的修复机制。综述强调了与衰老相关的微血管和血脑屏障完整性受损、神经细胞死亡增加、神经胶质细胞反应增强、炎症反应和免疫细胞浸润，所有这些都是缺血性中风进展的关键。通过审查最新研究，我们旨在全面了解神经血管单元在老龄人口缺血性中风中的作用，并讨论再生医学如何提供新的治疗策略，强调神经保护、神经再生和神经修复。这些方面对于针对老年人的临床干预至关重要，因为老年人在中风治疗中往往面临独特的挑战。综述强调了在中风研究和治疗中考虑衰老因素的重要性，因为神经血管单元内的细胞相互作用形成了一个复杂的系统，受到衰老过程的显著影响。在寻求有效的中风疗法时，这些联系不容忽视。再生医学的发展为中风治疗提供了新的视角，尤其是对于传统疗法可能效果较差或风险较高的老年人。这篇叙述性综述旨在弥补有关神经血管单元在老龄化背景下缺血性中风中的作用的知识空白，为开发能改善这一弱势群体预后的靶向疗法奠定基础。