The aim of this paper was to determine whether prolonged drinking of lead acetate-containing water by adult rats, which imitates environmental exposure to lead (Pb), affects some morphological and biochemical properties of rat brain microvessels. We noted a significant increase of lead level in capillaries and synaptosomes obtained from brains of rats under chronic toxicity conditions. Intravenously injected horseradish peroxidase (HRP) was used to evaluate the functional state of the blood-brain barrier (BBB). The results indicate that, systematically administered at low doses, lead induces BBB dysfunction. The changes, revealed in light microscopy and confirmed by electron microscopic studies, are typical for "leaky" microvessels, reported for variety of neuropathological conditions associated with BBB damage. Enhanced pinocytotic activity of the endothelial cells and the opening of interendothelial tight junctions, together with enormous phagocytizing action of the pericytes, are the most characteristic ultrastructural features noted. The presence of specific type of perivascular cells containing droplets of lipids in the cytoplasm, together with changes in phospholipid profile in brain capillaries, suggest that altered lipid composition of membranes may, at least in part, be responsible for changes in observed membrane permeability.

No abstract

Morphological studies of synaptosomes isolated from rat brains show that approximately 68% of the synaptosomes in these preparations contain synaptic vesicles (range, 62--72.5%). Approximately 30% of the synaptosomes contain mitochondria, and only less than 20% of the total mitochondria in good preparations are free and not enclosed in synaptic structures. The mitochondrial volume percent calculated on the basis of the measured cytochrome c content is 5% for synaptosomes isolated from anesthetized animals and 11% for synaptosomes isolated from unanesthetized animals. These numbers bracket the value of 8.7% obtained from electron micrographs. The volume percent of intrasynaptic vesicles is 1.5% as calculated from electron micrographs. The pH gradient between the extracellular pH and the mean intracellular pH is --0.45, as measured by equilibrium distributions of methylamine and dimethylamine, and --0.05, as determined by equilibrium distributions of 5,5-dimethyloxazolidine-2,4-dione and trimethylacetic acid. Analysis of these data shows that there cannot be a large pH gradient (alkaline inside) across the mitochondria, nor can the synaptic vesicle compartment be very large (less than 1.85%). Equilibrium distribution of [3H]triphenylmethylphosphonium ion in synaptosomal preparations gives a calculated apparent potential of --85 mV, in agreement with our previous value. Analysis of these data using the measured volumes of mitochondrial and intrasynaptic vesicular compartments (8.7 and 1.5%, respectively) gives a maximum possible transmitochondrial membrane potential of --59 mV.

No abstract

Crude (P2) synaptosomes derived from rats with acute hepatic encephalopathy (HE) induced with thioacetamide showed a slightly increased uptake of radiolabeled arginine (ARG) and a 2.5-fold enhanced conversion of newly taken-up ARG to both glutamate (GLU) and gamma-aminobutyric acid (GABA) as compared with control synaptosomes. Pulse treatment of the preloaded synaptosomes with a high potassium medium decreased their radioactive GLU and GABA content without affecting the content of the precursor ARG. This result, which was identical with control or HE preparations, appears to indicate that ARG contributes at least, in part, to the synthesis of neurotransmitter GLU or GABA. As measured in purified synaptosomal preparations, HE increased by about 50% the activities of arginase and ornithine-delta-aminotransferase--the two enzymes of the ARG to GLU shunt. It is postulated that increased conversion of ARG to GLU may compensate for excessive utilization of the latter amino acid as an ammonia trap during HE and, as such, may be considered as an adaptative response of the synaptic compartment to this pathological condition.