Wu Chunying, Tian Donghua, Feng Yue, Polak Paul, Wei Jingjun, Sharp Adam, Stankoff Bruno, Lubetzki Catherine, Zalc Bernard, Mufson Elliott J, Gould Robert M, Feinstein Douglas L, Wang Yanming
Department of Medical Chemistry and Pharmacognosy, University of Illinois at Chicago, USA, and Biologie des Interactions Neurones/Glie, Hopital de la Salpetriere, Paris, France.
J Histochem Cytochem. 2006 Sep;54(9):997-1004. doi: 10.1369/jhc.5A6901.2006. Epub 2006 May 18.
Myelin is a multilayered glial cell membrane that forms segmented sheaths around large-caliber axons of both the central nervous system (CNS) and peripheral nervous system (PNS). Myelin covering insures rapid and efficient transmission of nerve impulses. Direct visual assessment of local changes of myelin content in vivo could greatly facilitate diagnosis and therapeutic treatments of myelin-related diseases. Current histologic probes for the visualization of myelin are based on antibodies or charged histochemical reagents that do not enter the brain. We have developed a series of chemical compounds including (E,E)-1,4-bis(4'-aminostyryl)-2-dimethoxy-benzene termed BDB and the subject of this report, which readily penetrates the blood-brain barrier and selectively binds to the myelin sheath in brain. BDB selectively stains intact myelinated regions in wild-type mouse brain, which allows for delineation of cuprizone-induced demyelinating lesions in mouse brain. BDB can be injected IV into the brain and selectively detect demyelinating lesions in cuprizone-treated mice in situ. These studies justified further investigation of BDB as a potential myelin-imaging probe to monitor myelin pathology in vivo.
髓磷脂是一种多层神经胶质细胞膜，在中枢神经系统（CNS）和周围神经系统（PNS）的大口径轴突周围形成节段性鞘。髓磷脂覆盖可确保神经冲动的快速有效传递。在体内直接视觉评估髓磷脂含量的局部变化可极大地促进髓磷脂相关疾病的诊断和治疗。目前用于可视化髓磷脂的组织学探针基于不进入大脑的抗体或带电荷的组织化学试剂。我们已经开发了一系列化合物，包括（E，E）-1,4-双（4'-氨基苯乙烯基）-2-二甲氧基苯（称为BDB），本报告的主题，它很容易穿透血脑屏障并选择性地结合到脑中的髓鞘上。BDB选择性地染色野生型小鼠脑中完整的髓鞘区域，这使得可以描绘出小鼠脑中由双环己酮草酰二腙诱导的脱髓鞘病变。BDB可以静脉注射到脑中，并在原位选择性地检测双环己酮草酰二腙处理的小鼠中的脱髓鞘病变。这些研究证明进一步研究BDB作为一种潜在的髓磷脂成像探针以在体内监测髓磷脂病理学是合理的。
