Evaluation of large-sized brains for neurotoxic endpoints.

Sampling of large-sized brains (eg, dog, primate) for microscopic examination is frequently inadequate to detect localized neurotoxic injury. Furthermore, the examination of H&E-stained sections alone will often be insufficient for the detection of subtle neuropathogic alteration. It is imperative for any pathologist evaluating brain sections to have knowledge of microscopic neuroanatomy and to also have some understanding of basic neurochemistry. When a focus of degeneration is detected within the brain, the pathologist needs to ascertain not only the specific anatomic location of this focus but also the neuroanatomic regions that project to and receive output from the injured focus. Because of the complexity of brain circuitry and the fact that the brain contains many distinctive neuron populations, many more brain sections are required for adequate microscopic evaluation than for any other body organ. Deciding which and how many areas should be examined, microscopically, from a large size brain is often problematic. Although any sampling protocol will be influenced by what is known about the test chemical, it has been well established that certain regions of the brain (eg, hippocampus and other components of the limbic system, basal ganglia, Purkinje neurons) are more susceptible than others to a variety of physical, metabolic, and chemical insults. Knowledge of these regional sensitivities will assist in guiding the pathologist in the development of an adequate sampling protocol.