An in vivo model for studying function of brain tissue temporarily devoid of glial cell metabolism: the use of fluorocitrate.

The effect of intrastriatal injection of fluorocitrate on amino acid pattern, cell enzyme markers, and ultrastructural appearance was investigated. A dose of 1 nmol of fluorocitrate resulted in temporarily decreased levels of glutamine, glutamate, and aspartate, whereas the level of alanine was increased. The glutamine level was severely reduced after 4 h but was reversed after 24 h. The activity of different cellular enzyme markers did not change markedly after this dose. Ultrastructural changes in glial cells were observed, concomitant with the biochemical changes. A dose of greater than or equal to 2 nmol of fluorocitrate resulted in more marked and irreversible changes in amino acid levels. By 24-72 h after the injection of this dose, several marker enzyme activities decreased markedly. The ultrastructural changes affected the neurons as well as the glial cells and were not reversible. The use of microinjection of 1 nmol of fluorocitrate into the neostriatum of the rat to provide a model for studying transmitter amino acid metabolism in brain devoid of glial cell activity is discussed.