Sarkar Sumit, Raymick James, Schmued Larry C
Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR 72079, USA.
Toxicology Pathology Associates, Jefferson, AR 72079, USA.
Toxins (Basel). 2014 Apr 24;6(4):1453-70. doi: 10.3390/toxins6041453.
Neuronal and vascular brain components are interrelated morphologically, physiologically and developmentally. Due to this close interrelationship, it is often difficult to understand the cause and effect relationship between neuronal vs. vascular dysfunction and pathology. This review will discuss four of the more promising recent developments for detecting vascular pathology, and will compare them with the labeling pattern seen with markers of glial and neuronal pathology; following exposure to well characterized neurotoxicants. To detect the vascular dysfunction in the brain, we recently developed a Fluoro-Turquoise gelatin conjugate (FT-gel), a fluorescent probe that helps to delineate between healthy vs. sclerotic vessels. Similarly, we have investigated the potential for Fluoro-Gold to label in vivo all the endothelial cells in the brain as they co-localize with RECA, an endothelial cell marker. We have also developed Amylo-Glo, a fluorescent tracer that can detect neurotoxic A-beta aggregates in the brain. In this article, we will discuss the potential use of these novel histochemical markers to study the neurotoxicant induced brain. We will also discuss neurovascular strategies that may offer novel therapeutic opportunities for neurodegenerative disorders.
神经元和脑血管成分在形态学、生理学和发育过程中相互关联。由于这种紧密的相互关系，通常很难理解神经元功能障碍与血管功能障碍及病理之间的因果关系。本综述将讨论近期检测血管病理的四项更具前景的进展，并将它们与暴露于特征明确的神经毒素后，胶质细胞和神经元病理标志物的标记模式进行比较。为了检测大脑中的血管功能障碍，我们最近开发了一种荧光绿松石明胶共轭物（FT-凝胶），这是一种荧光探针，有助于区分健康血管与硬化血管。同样，我们研究了荧光金在体内标记大脑中所有内皮细胞的潜力，因为它们与内皮细胞标志物RECA共定位。我们还开发了淀粉样蛋白荧光标记物（Amylo-Glo），一种可以检测大脑中神经毒性β-淀粉样蛋白聚集体的荧光示踪剂。在本文中，我们将讨论这些新型组织化学标志物在研究神经毒素诱导的大脑方面的潜在用途。我们还将讨论可能为神经退行性疾病提供新治疗机会的神经血管策略。
