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Schmued L.C.,National Center for Toxicological Research (NCTR)
Brain Research | Year: 2016

Fluoro-gold: a new fluorescent retrograde axonal tracer with numerous unique properties: A new fluorescent dye, Fluoro-Gold, has been demonstrated to undergo retrograde axonal transport. Its properties include (1) intense fluorescence, (2) extensive filling of dendrites, (3) high resistance to fading, (4) no uptake by intact undamaged fibers of passage, (5) no diffusion from labeled cells, (6) consistent and pure commercial source, (7) wide latitude of survival times and (8) compatibility with all other tested neuro-histochemical techniques. © 1986. Fluoro-Jade C results in ultra high resolution and contrast labeling of degenerating neurons: The causes and effects of neuronal degeneration are of major interest to a wide variety of neuroscientists. Paralleling this growing interest is an increasing number of methods applicable to the detection of neuronal degeneration. The earliest methods employing aniline dyes were methodologically simple, but difficult to interpret due to a lack of staining specificity. In an attempt to circumvent this problem, numerous suppressed silver methods have been introduced. However, these methods are labor intensive, incompatible with most other histochemical procedures and notoriously capricious. In an attempt to develop a tracer with the methodological simplicity and reliability of conventional stains but with the specificity of an ideal suppressed silver preparation, the Fluoro-Jade dyes were developed. Fluoro-Jade C, like its predecessors, Fluoro-Jade and Fluoro-Jade B, was found to stain all degenerating neurons, regardless of specific insult or mechanism of cell death. Therefore, the patterns of neuronal degeneration seen following exposure to either the glutamate agonist, kainic acid, or the inhibitor of mitochondrial respiration, 3-NPA, were the same for all of the Fluoro-Jade dyes. However, there was a qualitative difference in the staining characteristics of the three fluorochromes. Specifically, Fluoro-Jade C exhibited the greatest signal to background ratio, as well as the highest resolution. This translates to a stain of maximal contrast and affinity for degenerating neurons. This makes it ideal for localizing not only degenerating nerve cell bodies, but also distal dendrites, axons and terminals. The dye is highly resistant to fading and is compatible with virtually all histological processing and staining protocols. Triple labeling was accomplished by staining degenerating neurons with Fluoro-Jade C, cell nuclei with DAPI and activated astrocytes with GFAP immunofluoresence. © 2005. article abstract: The development of novel tracers and associated histochemical methods has always been need driven. One such need was the development of tracers that could be administered to discrete brain regions in vivo to subsequently reveal neuronal connectivity via axonal transport of the tracer. One such compound is Fluoro-Gold (F-G), which can be used to demonstrate retrograde axonal transport. Advantages of this fluorescent tracer include brightness, sensitivity, contrast, stability, permanence and compatibility with multiple labeling studies. It may be applied to resolve either the afferent or efferent connections of brain regions of interest. Another need addressed was for a simple and definitive way to localize degenerating neurons in brain tissue sections. This led to the development of Fluoro-Jade B (FJ-B) and Fluoro-Jade C (FJ-C). Advantages of these fluorescent histochemical tracers include high specificity, resolution, contrast, stability and suitability for use in multiple labeling studies. These methods can be applied to detect both apoptotic and necrotic neuronal degeneration following a variety of insults including physical trauma, neurodegenerative disease and a wide variety of neurotoxicants. This article is part of a Special Issue entitled SI:50th Anniversary Issue. © 2016. Source

Pogribny I.P.,National Center for Toxicological Research (NCTR)
Experimental Oncology | Year: 2010

The development of cancer is a complex multifactorial process traditionally viewed as the stepwise accumulation of genetic alterations. However, recent advances in field of cancer research have established that all major human cancers, in addition to a large number of genetic alterations, exhibit prominent epigenetic abnormalities. This review presents current evidence that epigenetic alterations are not only key features of cancer cells, but they also may be key events in the initiation of carcinogenesis. The early appearance of cancer-linked epigenetic changes that are similar to those found in malignant cells provides a unique opportunity to use them as biomarkers in early cancer detection, indicators of carcinogenic exposure, and in the assessment of the carcinogenic potential of environmental chemical and physical agents. Copyright © Experimental Oncology, 2010. Source

Goodsaid F.M.,U.S. Food and Drug Administration | Mendrick D.L.,National Center for Toxicological Research (NCTR)
Science Translational Medicine | Year: 2010

The gap between development of exploratory biomarkers and their acceptance in drug development and regulatory review is a hurdle in the development of better therapies. The U.S. Food and Drug Administration has developed a regulatory process for biomarker qualification to accelerate the process by which new biomarkers are integrated in the development of therapies. Source

Pogribny I.P.,National Center for Toxicological Research (NCTR)
Breast Cancer Research | Year: 2010

Breast cancer is the most prevalent malignancy in women. The success of breast cancer treatment relies on the ability to detect the disease and correct molecular abnormalities at an early stage of disease development. A recent article describes a marked decrease in the levels of ferroportin in breast cancer. More importantly, the presented results demonstrate convincingly the incredible diagnostic and prognostic value of ferroportin and hepcidin gene expression in breast cancer and suggest that determination of these two molecular markers may be used as guidance toward individualized therapy for breast cancer patients. © 2010 BioMed Central Ltd. Source

Bowyer J.F.,National Center for Toxicological Research (NCTR)
Journal of visualized experiments : JoVE | Year: 2012

This video presentation was created to show a method of harvesting the two most important highly vascular structures, not residing within the brain proper, that support forebrain function. They are the cerebral surface (superficial) vasculature along with associated meninges (MAV) and the choroid plexus which are necessary for cerebral blood flow and cerebrospinal fluid (CSF) homeostasis. The tissue harvested is suitable for biochemical and physiological analysis, and the MAV has been shown to be sensitive to damage produced by amphetamine and hyperthermia. As well, the major and minor cerebral vasculatures harvested in MAV are of potentially high interest when investigating concussive types of head trauma. The MAV dissected in this presentation consists of the pial and some of the arachnoid membrane (less dura) of the meninges and the major and minor cerebral surface vasculature. The choroid plexus dissected is the structure that resides in the lateral ventricles as described by Oldfield and McKinley. The methods used for harvesting these two tissues also facilitate the harvesting of regional cortical tissue devoid of meninges and larger cerebral surface vasculature, and is compatible with harvesting other brain tissues such as striatum, hypothalamus, hippocampus, etc. The dissection of the two tissues takes from 5 to 10 min total. The gene expression levels for the dissected MAV and choroid plexus, as shown and described in this presentation can be found at GSE23093 (MAV) and GSE29733 (choroid plexus) at the NCBI GEO repository. This data has been, and is being, used to help further understand the functioning of the MAV and choroid plexus and how neurotoxic events such as severe hyperthermia and AMPH adversely affect their function. Source

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