Title:Systemic Administration of Fluoro-Gold for the Histological Assessment of Vascular Structure, Integrity and Damage
Volume: 11
Issue: 1
Author(s): John F. Bowyer, Karen M. Tranter, Sumit Sarkar, James Raymick, Joseph P. Hanig and Larry C. Schmued
Affiliation:
Keywords:
Fluoro-Gold, Blood-brain barrier, Vascular elements, Hemorrhage, Kainate, Amphetamine.
Abstract: Fluoro-Gold (F-G) has been used extensively as a fluorescent retrograde neuronal-track tracer in the past. We
now report that intraperitoneal administration of 10 to 30 mg/ kg of F-G from 30 min to 7 days prior to sacrifice labels
vascular endothelial cells of the brain, choroid plexus and meninges and can be used to assess vascular integrity and
damage. F-G vascular labeling co-localized with rat endothelial cell antigen (RECA-1) in the membrane. F-G also
intensely labeled the nuclei of the endothelial cells, and co-localized with propidium iodide staining of these nuclei. As
well, the administration of F-G during neurotoxic insults produced by amphetamine, kainic acid or “penetrating” wound
to the brain can detect where vascular leakage/ hemorrhage has occurred. Histological methods to detect F-G labeled brain
vasculature were performed in the same manner as that used for fluorescent visualization of neuronal elements labeled
with F-G after perfusion fixation and coronal sectioning (15 to 40 µm) of the brain. This in vivo F-G labeling of
endothelial cells and their nuclei yields a clear picture of the integrity of the vasculature and can be used to detect changes
in structure. Vascular leaks after “penetrating” wounds through the cortex and striatum, hyperthermic amphetamine
exposure or excitotoxic kainate exposure were detected by F-G in the extracellular space and via parenchymal F-G
subsequently labeling the terminals and neurons adjacent to the lesioned or damaged vasculature. Further studies are
necessary to determine the extent of the leakage necessary to detect vasculature damage. Visualization of the F-G labeling
of vasculature structure and leakage is compatible with standard fluorescent immuno-labeling methods used to detect the
presence and distribution of a protein in histological sections. This method should be directly applicable to studying brain
vascular damage that occurs in the progression of Alzheimer’s disease, diabetes and for monitoring the brain vascular
changes during development.
