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缺血性卒中中的血管生成、神经发生和神经可塑性

Angiogenesis, neurogenesis and neuroplasticity in ischemic stroke.

作者信息

Font M Angels, Arboix Adriá, Krupinski Jerzy

机构信息

Fundació IDIBELL, Barcelona, Spain.

出版信息

Curr Cardiol Rev. 2010 Aug;6(3):238-44. doi: 10.2174/157340310791658802.

Abstract

Only very little is know about the neurovascular niche after cardioembolic stroke. Three processes implicated in neurorepair: angiogenesis, neurogenesis and synaptic plasticity, would be naturally produced in adult brains, but also could be stimulated through endogen neurorepair phenomena. Angiogenesis stimulation generates new vessels with the aim to increase collateral circulation. Neurogenesis is controlled by intrinsic genetic mechanisms and growth factors but also ambiental factors are important. The leading process of the migrating neural progenitor cells (NPCs) is closely associated with blood vessels, suggesting that this interaction provides directional guidance to the NPCs. These findings suggest that blood vessels play an important role as a scaffold for NPCs migration toward the damaged brain region. DNA microarray technology and blood genomic profiling in human stroke provided tools to investigate the expression of thousands of genes. Critical comparison of gene expression profiles after stroke in humans with those in animal models should lead to a better understanding of the pathophysiology of brain ischaemia. Probably the most important part of early recovery after stroke is limited capacity of penumbra/infarct neurones to recover. It became more clear in the last years, that penumbra is not just passively dying over time but it is also actively recovering. This initial plasticity in majority contributes towards later neurogenesis, angiogenesis and final recovery. Penumbra is a principal target in acute phase of stroke. Thus, the origin of newly formed vessels and the pathogenic role of neovascularization and neurogenesis are important unresolved issues in our understanding of the mechanisms after stroke. Biomaterials for promoting brain protection, repair and regeneration are new hot target. Recently developed biomaterials can enable and increase the target delivery of drugs or therapeutic proteins to the brain, allow cell or tissue transplants to be effectively delivered to the brain and help to rebuild damaged circuits. These new approaches are gaining clear importance because nanotechnology allows better control over material-cell interactions that induce specific developmental processes and cellular responses including differentiation, migration and outgrowth.

摘要

关于心源性栓塞性中风后的神经血管微环境,我们所知甚少。神经修复涉及的三个过程,即血管生成、神经发生和突触可塑性,在成人大脑中会自然发生,但也可以通过内源性神经修复现象来刺激。刺激血管生成会产生新的血管,以增加侧支循环。神经发生受内在遗传机制和生长因子控制,但环境因素也很重要。迁移的神经祖细胞(NPCs)的主要过程与血管密切相关,这表明这种相互作用为NPCs提供了定向引导。这些发现表明,血管在NPCs向受损脑区迁移的过程中起着重要的支架作用。人类中风的DNA微阵列技术和血液基因组分析提供了研究数千个基因表达的工具。将人类中风后的基因表达谱与动物模型中的进行关键比较,应该能更好地理解脑缺血的病理生理学。中风后早期恢复可能最重要的部分是半暗带/梗死神经元的恢复能力有限。近年来越来越清楚的是,半暗带并非只是随着时间被动死亡,它也在积极恢复。这种最初的可塑性在很大程度上有助于后期的神经发生、血管生成和最终恢复。半暗带是中风急性期的主要靶点。因此,新形成血管的起源以及新生血管形成和神经发生的致病作用,是我们理解中风后机制时重要的未解决问题。促进脑保护、修复和再生的生物材料是新的热门靶点。最近开发的生物材料能够实现并增加药物或治疗性蛋白质向大脑的靶向递送,使细胞或组织移植能够有效地递送至大脑,并有助于重建受损回路。这些新方法正变得越来越重要,因为纳米技术能够更好地控制诱导特定发育过程和细胞反应(包括分化、迁移和生长)的材料-细胞相互作用。

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