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Originally published as JHC exPRESS on May 18, 2006.
doi:10.1369/jhc.5A6901.2006
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Journal of Histochemistry and Cytochemistry
Volume 54 (9): 997-1004, 2006
Copyright ©The Histochemical Society, Inc.

A Novel Fluorescent Probe That Is Brain Permeable and Selectively Binds to {alpha}Myelin

Chunying Wu1, Donghua Tian1, Yue Feng, Paul Polak, Jingjun Wei, Adam Sharp, Bruno Stankoff, Catherine Lubetzki, Bernard Zalc, Elliott J. Mufson, Robert M. Gould, Douglas L. Feinstein and Yanming Wang

Departments of Medicinal Chemistry and Pharmacognosy (CW,JW,YMW), Anethesiology (PP,AS,DLF), and Anatomy and Cell Biology (RMG), University of Illinois at Chicago, Chicago, Illinois; Department of Pharmacology, Emory University, Atlanta, Georgia (DT,YF); Biologie des Interactions Neurones/Glie, Hopital de la Salpetriere, Paris, France (BS,CL,BZ); and Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois (EJM)

Correspondence and present address: Yanming Wang, Case Center for Imaging Research, Case Western University, 11100 Euclid Avenue, Cleveland, OH 44106. E-mail: ywang{at}uhrad.com

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. (J Histochem Cytochem 54:997–1004, 2006)

Key Words: multiple sclerosis • myelin • biomarkers • demyelination • blood–brain barrier


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