


Introduction | Scope of Stained Elements | Compare With H&E | Silver Degeneration Staining Evolution
Neonatal Cell Death (apoptosis) | Neurotoxicity Detection Paper | Planning a Neurotoxicity Experiment
The disintegrative degeneration stain has roots in silver staining methods that have been used for years in numerous ways to render a variety of physical and biological features visible. In biological tissue, histologic protocols use silver to visualize diverse structures or features: reticulin, melanin, fungi, chromosome bands, nucleolar organizing regions, and different features in the nervous system.
A comparison of the protocols reveals that silver is "directed" to stain any given feature by the type of fixation, pretreatment ('mordanting'), the composition of the silver-containing solution(s), and the form of development (reduction). Keystone methods such as those of Bodian and Bielschowsky exploit the nervous system's affinity for silver (argyrophilia). The beginning of a new era in brain research came with the recognition that distinct silver-impregnated morphologic changes occurring to damaged axons could be used for tracing axon pathways in experimental animals with specifically placed lesions. Improvements in staining methods to selectively impregnate the disintegrating axons but leave normal axons unstained were achieved by Nauta and Gygax (pioneers with these procedures) and spawned a host of method variations known as the "Nauta" methods. Of these, the Fink-Heimer and deOlmos' cupric-silver methods were able to unambiguously demonstrate disintegrating synaptic terminals, thereby allowing complete tracing of axon pathways.
The late 70's and 80's witnessed innovative applications of these techniques. The "silver methods" once used to trace axon pathways were evolved to become indicators of the extreme endpoint of neurotoxicity: disintegrative degeneration of neurons induced by neurotoxic chemicals administered systemically. The hallmark of neurotoxic substances is the selectivity with which each destroys specific populations or sub-populations of neurons. The high contrast and sensitivity of the disintegrative degeneration stains greatly facilitates the screening process to detect these affected populations, especially when there is no basis for knowing where in the brain to look for damage. More recently, the disintegrative degeneration stain is being further exploited to chart the neuron populations undergoing programmed cell death in the developing brain.
The above is an excerpt from the paper:
Toxicologic Pathology, vol. 28, pp 70-83, 2000
Application of Silver Degeneration Stains for Neurotoxicity Testing
Robert C. Switzer III, PhD
Neuroscience Associates, Knoxville, TN 37934
View the complete paper here.
Introduction | Scope of Stained Elements | Compare With H&E | Silver Degeneration Staining Evolution
Neonatal Cell Death (apoptosis) | Neurotoxicity Detection Paper | Planning a Neurotoxicity Experiment
For futher reference, please see: Stains