Neurochemical and biochemical assays

Though some very elegant methods are now available to study the biochemistry of the brain and nervous system, none has yet discovered any generalized marker chemicals that will serve as reliable indicators or early warnings of neurotoxic actions or potential actions. There are, however, some useful methods. Before looking at these, however, one should understand the basic problems involved. 

Normal biochemical events surroimding the maintenance and functions of the nervous system center aroimd energy metabolism biosynthesis of macromolecules and neurotransmitter synthesis, storage, release, uptake, and degradation. Measurement of these events is complicated by the sequenced nature of the components of the nervous system and the transient and labile nature of the moieties involved. Use of measurements of alternations in the these fimctions as indicators of neurotoxicity is further complicated by our lack of a complete imderstanding of the normal operation of these systems and by the multitude of day-to-day occurrences (such as diurnal cycle, diet, temperature, age, sex, and endocrine status) that are constantly modulating the baseline system. For detailed discussions of these difficulties, the reader is advised to see Damstra and Bondy [37,38]. 

Note for Guidance on Safety Pharmacology Studies in Medicinal Product Development, 1998. 

Comprehensive observational assessment la. A systematic, quantitative procedure for assessing the behavioral and physiologic state of the mouse, Psychopharmacologia, Berlin, 1968,13 222-257. 

A neuromuscular screen for use in industrial toxicology, /. Toxicol. Environ. Health, 1982,9 691-704. 

---