Neurochemical Applications

The potential applications of the precolumn denvatization techniques in neurochemistry are, of course, considerable. A few examples concerning release of amino acids m vitro and in vivo and levels of ammo acids in CNS fluids will be reported Finally, the usefulness of the method m the clinical routine, i e. for determination of amino acids in cerebrospinal fluid, will be touched upon briefly. 

In earlier studies, the efflux of exogenously applied, radioactive amino acids was most commonly studied (Katz et al, 1969, Snnivasan et al., 1969). The high sensitivity of the postcolumn denvatization technique with fluorigenic derivatization made it possible to follow the release of a range of endogenous amino acids during various conditions (Norris et al., 1980). Moreover, the precolumn derivatization techniques (Lindroth and Mopper, 1979, Ejnarsson et al, 1983) enable measurement of subpicomol amounts of amino acids. 

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Kissinger PT, Bruntlett CS, Shoup RE. Neurochemical applications of liquid chromatography with electrochemical detection. Life Sci 1981 28 455-65. 

Neurochemical Applications of the Double-Isotope Dansyl Microassay... 

The electrochemical methods that have evolved for neurochemical applications have several advantages that make them ideally suited to the task for which they are intended the methods are selective, sensitive, and rapid. Nevertheless, the key advantages that will be highlighted in this chapter are derived from the micrometer physical dimensions of the microelectrodes themselves (Fig. 1). Today, the majority of in vivo electrochemistry is conducted in the brain with microelectrodes constructed with individual, or a... 

The electrode has particular advantages for neurochemical applications. It would be cumbersome at best to titrate CAs oxidatively as they pass from the end of a chromatographic column and impossible to do so in a living brain system. But, in principle, we can make an electrode of any size and shape, place it in the flowing eluent from a column or implant it in the CNS, and continuously or intermittently monitor the current and thus the concentration of electro-oxidizable species. Electrons cannot be transferred in solution over distances greater than a few molecular diameters, and this fact means that electroactiVe species must be very close to the surface of an electrode to undergo reaction. This finite spatial resolution is especially useful for in vivo applications. With very small electrodes and short electrolysis times, minute brain regions can be sampled. 

This section will explore the quantitative behavior of current-potential curves (voltammetry) and steady-state current measurements in flowing solution prior to considering liquid chromatographic assays. A similar examination of quiet solutions is reserved for the section on in vivo measurements. (In this and all subsequent voltammetry discussions, only oxidation reactions are treated, not because reductions are unimportant, but because there are to date few, if any, neurochemical applications.)... 

Although such electrodes have continued to be used as implantable micro-electrodes in neurochemical applications and are commercially available, they are not specifically manufactured for use with HPLC or CE. 

M. Tomi and K. Hosoya. Application of magnetically isolated rat retinal vascular endothelial cells for the determination of transporter gene expression levels at the inner blood-retinal barrier. J. Neurochem. 91 1244—1248 (2004). 

A major component of a GC system is the detector. The general principles of detectors commonly used in neurochemical studies will be discussed here, and specific applications will be covered later in the chapter. 

A list of APCI applications to a number of chemicals of neurochemical interest is provided in Table 6-2. 

Millard CB and Broomfield CA. Anticholinesterases Medical applications of neurochemical principles. J Neurochem 1995 64 1909-1918. 

The modern interest in electrochemical detectors for liquid chromatography was stimulated by the recognition that this technique was ideal for the study of aromatic metabolism in the mammalian central nervous system. Most of the papers published during the past 20 years have focused on applications of the LCEC technique to neurochemical problems. Since the First commercial detectors became available in 1974, a number of other areas of application have been explored as well. The trade publication Current Separations provides a useful... 

One of the first applications of HPLC in the clinical field was the quantitation of theophylline in asthmatic infants. This highly accurate measurement was an important test because of the very low amount of sample required and the accuracy of the determination (see Fig. 1-10). More recent clinically related HPLC separations include drugs and drug metabolites, neurochemicals and their metabolites, histamines, thyroid hormones, and enkephalins. The earliest bioresearch applications of HPLC included the determination of peptides, proteins, and amino acids. Application of HPLC to the analysis of these compounds remains important, as indicated by the rapid growth in references (Fig. 1-11). Bioresearch remains one of the most rapidly expanding growth areas of LC. 

Higashi S, Moore DJ, Colebrooke RE, Biskup S, Dawson VL, Arai H, Dawson TM, Emson PC (2007b) Expression and localization of Parkinson s disease-associated leucine-rich repeat kinase 2 in the mouse brain. J Neurochem 100 368-381 Higgins GA, Jacobsen H (2003) Transgenic mouse models of Alzheimer s disease phenotype and application. Behav Pharmacol 14 419—438... 

Giacobini, E. (1998). Invited review cholinesterase inhibitors for Alzheimer s disease therapy from tacrine to future applications. Neurochem. Int. 32 413-19. 

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