Fluoro-Jade: Novel fluorochromes for detecting toxicant-induced neuronal degeneration

Two anionic fluorescein derivatives can be used for the simple and definiti ve localization of neuronal degeneration in brain tissue sections. Initial work on the first generation fluorochrome, Fluoro-Jade, demonstrated the ut ility of this compound for the detection of neuronal degeneration induced b y a variety of well-characterized neurotoxicants, including kainic acid, 3- nitropropionic acid, isoniazid, ibogaine, domoic acid, and dizocilpine male ate (MK-801). After validation, the tracer was used to reveal previously un reported sites of neuronal degeneration associated with 1-methyl-4-phenyl-1 ,2,3,6-tetrahydropyri (MPTP), methamphetamine, and d-fenfluramine. Prelimin ary findings with a second generation fluorescein derivative, Fluoro-Jade B , suggest that this tracer results in staining of optimal contrast and reso lution in animals dosed with kainic acid. These 2 tracers can be combined w ith other histologic methods, including immunofluoresence and fluorescent N issl stains. Recent preliminary findings on a number of specialized applica tions of Fluoro-Jade include the detection of apoptosis, amyloid plaques, a strocytes, and dead cells in tissue culture.