3-3--diethylthiatricarbocyanine and Demyelinating-Diseases

Myelination is one of the fundamental biological processes in the development of vertebrate nervous system. Disturbance of myelination is found to be associated with progression in many neurological diseases such as multiple sclerosis. Tremendous efforts have been made to develop novel therapeutic agents that prevent demyelination and/or promote remyelination. These efforts need to be accompanied by the development of imaging tools that permit direct quantification of myelination in vivo. In this work, we describe a novel near-infrared fluorescence imaging technique that is capable of direct quantification of myelination in vivo. This technique is developed based on a near-infrared fluorescent probe, 3,3'-diethylthiatricarbocyanine iodide (DBT) that readily enters the brain and specifically binds to myelinated fibers. In vivo imaging studies were first conducted in two animal models of hypermyelination and hypomyelination followed by longitudinal studies in the cuprizone-induced demyelination/remyelination mouse model. Quantitative analysis suggests that DBT is a sensitive and specific imaging probe of myelination, which complements other current myelin-imaging modalities and is of low cost.

Topics: Analysis of Variance; Animals; Benzothiazoles; Carbocyanines; Corpus Callosum; Cuprizone; Demyelinating Diseases; Disease Models, Animal; Longitudinal Studies; Mice; Mice, Inbred C57BL; Mice, Neurologic Mutants; Mice, Transgenic; Myelin Basic Protein; Myelin Proteolipid Protein; Myelin Sheath; Permeability; Protein Binding; Proto-Oncogene Proteins c-akt; Spectroscopy, Near-Infrared; Time Factors