The use of recently developed histochemical markers for localizing neurotoxicant induced regional brain pathologies.
Neuronal and vascular brain components are interrelated morphologically, physiologically and developmentally. Due to this close interrelationship, it is often difficult to understand the cause and effect relationship between neuronal vs. vascular dysfunction and pathology. This review will discuss four of the more promising recent developments for detecting vascular pathology, and will compare them with the labeling pattern seen with markers of glial and neuronal pathology; following exposure to well characterized neurotoxicants. To detect the vascular dysfunction in the brain, we recently developed a Fluoro-Turquoise gelatin conjugate (FT-gel), a fluorescent probe that helps to delineate between healthy vs. sclerotic vessels. Similarly, we have investigated the potential for Fluoro-Gold to label in vivo all the endothelial cells in the brain as they co-localize with RECA, an endothelial cell marker. We have also developed Amylo-Glo, a fluorescent tracer that can detect neurotoxic A-beta aggregates in the brain. In this article, we will discuss the potential use of these novel histochemical markers to study the neurotoxicant induced brain. We will also discuss neurovascular strategies that may offer novel therapeutic opportunities for neurodegenerative disorders.
Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR 72079, USA. Sumit.Sarkar@fda.hhs.gov.
Sumit
S
Sarkar
Toxicology Pathology Associates, Jefferson, AR 72079, USA. James.Raymick@fda.hhs.gov.
James
J
Raymick
Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR 72079, USA. Larry.Schmued@fda.hhs.gov.
Larry C
LC
Schmued
D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005456:Fluorescent Dyes; D006801:Humans; D008856:Microscopy, Fluorescence; D055806:Microvessels / Q000378:metabolism / Q000473:pathology*; D019636:Neurodegenerative Diseases / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D061848:Optical Imaging / Q000379:methods*; D058225:Plaque, Amyloid; D011237:Predictive Value of Tests
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D005456:Fluorescent Dyes