ABSTRACT
INTRODUCTION The Swiss physician Paracelsus, also known as Theophrastus Phillipus Auroleus Bombastus von Hohenheim (1493-1541), based his life work on a simple philosophy: “All things are poison and nothing is without poison; only the dose makes a thing a poison.” In 1813 the Spanish physician Mathieu Orfi la incorporated this principle into Toxicologie Générale , the fi rst comprehensive review of the clinical and pathology effects of known poisons on the human body. Today, almost two centuries later, toxicologists in government agencies, academic institutions, and private industry continue to test important hypotheses about the toxic effects of chemical agents on the central and peripheral nervous systems of humans and experimental animals. Modern methods for quantitative and semi-quantitative analysis of tissue, with support from high-resolution microscopy, computer-based imaging, and immunohistochemistry, provide the foundation for conclusions about changes in the number of discrete cell populations (apoptosis, proliferation); neuritic fi bers and blood vessels (angiogenesis, sprouting, degeneration); absorptive membranes surfaces; and volumes of cells and tissues (atrophy, hypertrophy). This chapter reviews quantitative (design-based stereology) and semi-quantitative (video densitometry) techniques in contemporary neurotoxicology for the assessment of neural damage and neuroprotective effects at the organ, tissue, cellular, and sub-cellular levels.
