Methods to identify and characterize developmental neurotoxicity for human health risk assessment. II: neuropathology.

Abstract

Neuropathologic assessment of chemically induced developmental alterations in the nervous system for regulatory purposes is a multifactorial, complex process. This calls for careful qualitative and quantitative morphologic study of numerous brains at several developmental stages in rats. Quantitative evaluation may include such basic methods as determination of brain weight and dimensions as well as the progressively more complex approaches of linear, areal, or stereologic measurement of brain sections. Histologic evaluation employs routine stains (such as hematoxylin and eosin), which can be complemented by a variety of special and immunohistochemical procedures. These brain studies are augmented by morphologic assessment of selected peripheral nervous system structures. Studies of this nature require a high level of technical skill as well as special training on the part of the pathologist. The pathologist should have knowledge of normal microscopic neuroanatomy/neuronal circuitry and an understanding of basic principles of developmental neurobiology, such as familiarity with the patterns of physiologic or programmed cell de

Diminished experience-dependent neuroanatomical plasticity: evidence for an improved biomarker of subtle neurotoxic damage to the developing rat brain.

“…One way is use a variety of sensitive neuropathological techniques to assess the integrity of neural circuits and associated metabolic support at the close of a key stage (Garman et al 2001). Here, as an alternative way to define healthy development, we evaluate experience-dependent plasticity, a late component of brain development that emerges after basic circuitry has formed and remains active into maturity (Black and Greenough 1986).…”

Introduction: reviews of environmental health, 2001.

“…Because of the growing awareness of the effects of toxicants on the nervous system, EHP considers these issues important and has included four review papers developed from the working group convened by ILSI-RSI. In these papers, the authors identify and describe methods to detect and characterize developmental neurotoxicity in laboratory animal in the areas of behavioral testing, neuropathology, and pharmacokinetics (15)(16)(17)(18).…”

Developmental Neurotoxicology: History and Outline of Developmental Neurotoxicity Study Guidelines

“…3-6). The size of brains is also reported to vary widely among individuals in the same days of age during the lactation period depending on prenatal gestation lengths and/or litter sizes 78) . Thus, neuropathologists need to devise appropriate methodology for sectioning brain tissue with variable sizes at accurately the same plane for neuropathological examinations and morphometrics.…”