A Versatile Murine Model of Subcortical White Matter Stroke for the Study of Axonal Degeneration and White Matter Neurobiology
A Versatile Murine Model of Subcortical White Matter Stroke for the Study of Axonal Degeneration and White Matter Neurobiology
复制标题
DOI：
10.3791/53404
复制
发表时间：
2016-03-01
影响因子：
1.2
通讯作者：
Hinman, Jason D.
中科院分区：
文献类型：
--
作者：
Nunez, Stefanie;Doroudchi, M. Mehdi;Hinman, Jason D.
影响白色物质的卒中占临床卒中表现的25%，以可能高5-10倍的速率无声地发生，并且显著促进血管性痴呆的发展。局灶性白色脑卒中的模型很少，缺乏合适的模型阻碍了对这类脑卒中后损伤反应和修复的神经生物学机制的理解。其他皮质下卒中模型的主要局限性是它们没有将梗死局限于白色物质或主要在非鼠物种中验证。这限制了应用各种各样的鼠类研究工具来研究白色脑卒中的神经生物学的能力。在这里，我们提出了一种方法，可靠的生产局灶性中风的小鼠白色的问题，使用局部注射不可逆的eNOS抑制剂。我们还提出了几个变化的一般协议，包括两个独特的立体定向的变化，逆行神经元示踪，以及新鲜的组织标记和解剖，大大扩展了这种技术的潜在应用。这些变化允许多种方法来分析这种常见且研究不足的中风形式的神经生物学效应。
Stroke affecting white matter accounts for up to 25% of clinical stroke presentations, occurs silently at rates that may be 5-10 fold greater, and contributes significantly to the development of vascular dementia. Few models of focal white matter stroke exist and this lack of appropriate models has hampered understanding of the neurobiologic mechanisms involved in injury response and repair after this type of stroke. The main limitation of other subcortical stroke models is that they do not focally restrict the infarct to the white matter or have primarily been validated in non-murine species. This limits the ability to apply the wide variety of murine research tools to study the neurobiology of white matter stroke. Here we present a methodology for the reliable production of a focal stroke in murine white matter using a local injection of an irreversible eNOS inhibitor. We also present several variations on the general protocol including two unique stereotactic variations, retrograde neuronal tracing, as well as fresh tissue labeling and dissection that greatly expand the potential applications of this technique. These variations allow for multiple approaches to analyze the neurobiologic effects of this common and understudied form of stroke.