The effects of inhalation exposure of rats methyl bromide (MB) on dopamine (DA), homovanillic acid (HVA), norepinephrine (NE), 3-methoxy-4-hydroxyphenylglycol (MHPG), serotonin (5HT), and 5-hydroxyindoleacetic acid (5HIAA) concentrations of various brain regions (striatum, hypothalamus, frontal cortex, midbrain, and medulla oblongata) were investigated. Rats received a single 8 hr exposure to MB, and amines and metabolites were separated by a reverse-phase HPLC, and were quantified via native fluorescence. An exposure to 100 ppm MB decreased tissue levels of DA and NE in all brain areas at 0 or 2 hr following exposure. HVA and MHPG contents were significantly increased in almost all brain regions. In a second study, rats were exposed to four concentrations of MB ranging from 31-250 ppm, and monoamine and metabolite levels in brain regions measured immediately after the exposure. Again, there were dose-dependent decreases of DA and NE, and increases in HVA and MHPG. Less clear changes in 5 HT and 5HIAA contents were observed. These data suggest that alterations of catecholamine metabolism may be a factor in MB-induced neurotoxicity.

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PubMedDate not supplied

Inhibition of tyrosine hydroxylase activity by methyl bromide exposure.

Rats were exposed to methyl bromide gas (16-250 ppm) for 8 hr, and tyrosine hydroxylase (TH) activity in the striatum, hypothalamus, frontal cortex, midbrain, and medulla oblongata was measured in brain homogenates from exposed rats, and in vivo following administration of decarboxylase inhibitor. Exposure to methyl bromide dose-dependently inhibited both in vitro and in vivo TH activity. Of the five brain areas, TH activity in the hypothalamus was most sensitive to methyl bromide. The time course of enzyme inhibition after exposure was similar to those of decreases in catecholamine concentrations, locomotor activity change, and body temperature reported previously. These results suggest methyl bromide reduces catecholaminergic neuronal activity in the brain via inhibition of TH activity.

Animals↗

PubMedDate not supplied

Effects of subchronic exposure to toluene on working and reference memory in rats.

Rats that had inhaled 600 ppm of toluene vapor 24 h a day for 50 days after weaning at 3 weeks of age were trained in a radial-arm maze with a 4-out-of-8 baiting procedure, and their performance based upon reference and/or working memory was compared with that of air-exposed control animals during the early stage of acquisition. Pharmacological challenge testing was also conducted after completing a total of 48 training sessions; the effects of scopolamine and methylscopolamine on the maze performance were measured after acute i.p. administration to determine the long-lasting effects of toluene exposure. During the acquisition stage, toluene-exposed rats made a significantly smaller number of reference memory errors (entries into "never-baited" arms) and total arm entries than the control rats. No significant effects of exposure were observed for working memory errors (reentries into "already-entered" arms). During the pharmacological challenge testing, only scopolamine increased both types of errors significantly. No significant differences due to toluene exposure were revealed.

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PubMedDate not supplied

Effects of short-term toluene exposure on ligand binding to muscarinic acetylcholine receptors in the rat frontal cortex and hippocampus.

Changes in the binding affinity of the muscarinic acetylcholine receptor agonist carbamylcholine were determined in membranes isolated from the brains of rats exposed to toluene at concentrations of 500-2,000 ppm for 6 h. Membrane fractions of the frontal cortex and hippocampus were prepared and agonist-binding affinities were determined by measuring the displacement of [3H]N-methyl scopolamine-binding activity by carbamylcholine. In the frontal cortex, the affinity of high-affinity carbamylcholine binding was reduced following exposure to toluene at a concentration of 1000 ppm or higher. However, in the hippocampus, the affinity of high-affinity binding of carbamylcholine was increased following exposure to toluene. These observations suggest that toluene exposure affects binding affinity of carbamylcholine, and the effect differs by brain region.

Animals↗

PubMedDate not supplied

Mass psychogenic systemic illness in school children in relation to the Tokyo photochemical smog.

To clarify the pathogenic mechanism of epidemics with acute systemic neurobehavioral illness associated with photochemical air pollution in Japan, we re-examined our past records in sixteen junior high school children, and compared them with major epidemics that occurred in 1970-1972 during which time Japanese society faced a new and unusual type of air pollution ("Tokyo smog"). Dysfunction of alveolar-arterial gas exchange, together with respiratory alkalosis, was newly found in these children, who suffered from chest discomfort, ocular irritation, emotional distress, tetany, and unconsciousness. It was concluded that anxiety reaction, precipitated by the physical effects of photochemical oxidants and athletic performance, possibly led to many outbreaks of mass psychogenic systemic illness (hyperventilation syndrome) among school children.

Adolescent↗

PubMedDate not supplied

Association between hemosiderin deposition and blood vessel regression during involution of foreign-body granuloma. Histochemical and ultrastructural study.

We have characterized the sequence of events resulting in vessel occlusion and stasis of blood flow during involution of a foreign-body granuloma using histochemistry and electron microscopy. In the microvascular bed of the granulation tissue accompanying the progressive resorption of an implanted collagen sponge, endothelial cells protruded into the vascular lumen, resulting in the occlusion of the lumens of venules and capillaries. Examination of sections stained by the TUNEL method showed brown-yellow stained structures in the vascular lumen during regression of blood vessels. However, the ultrastructural profiles of endothelial cells effectively involved in the vessel occlusion showed none of the cardinal morphological features of apoptosis. These endothelial cells which displayed remarkable indentations of their nuclei in the form of nuclear pinches and/or deep pockets bulged conspicuously into the lumen. Such endothelial cells served as effective valves by protruding into the lumens of small blood vessels, and eventually the vessels were completely plugged by red blood cells. However, protruding endothelial cells subsequently shed into the vascular lumen by deviating themselves from the constitution of the vessel wall. The endothelial cells undergoing apoptosis were removed by intraluminal macrophages. Between the 130 and 140 day, the occurrence of small vessels tightly packed with erythrocytes reached a peak value in the granulation tissue and was accompanied by hemosiderin deposits. The plugged vessels were frequently associated with erythrocyte extravasation, leading to openings between degenerated endothelial cells due to the disappearance of endothelial cytoplasmic projections. Extravasated erythrocytes were rapidly eliminated by phagocytic cells such as mononuclear macrophages and multinucleated giant cells, and ended as hemosiderin deposits in granulation and/or scar tissue at the end of the experimental period (130-140 days). The morphological analysis of this regression sequence suggests that the protrusion of endothelial cells with the nuclear deformation is a mechanism contributing to the occlusion of blood vessels and consequently leads to erythrocyte extravasation.

Animals↗

PubMedDate not supplied

Significant changes in monoamines in rat brain induced by exposure to methyl bromide.

Rats were exposed to methyl bromide (MB) gas for 24 hr or 3 weeks continuously. Norepinephrine (NE), dopamine (DA), serotonin (5-HT), acetylcholine (ACh), cyclic AMP (cAMP) and cyclic GMP (cGMP) contents in dissected brain regions were measured after MB exposure. MB produced remarkable reduction in NE contents of hypothalamus and cortex + hippocampus at 100 ppm or higher concentration after 24 hr exposure and at 10 ppm after 3 weeks exposure. At the same concentration of MB, DA, 5-HT and ACh contents were only slightly affected by the exposure. Change in neurotransmitter content was specific to NE. MB-induced changes in NE contents lasted for at least 24 hr after the cessation of exposure. cAMP was increased and cGMP was reduced by MB exposure. These results suggested that MB might have enhanced the stimulation of DA receptors and weakened the stimulation of ACh receptors in the brain.

Acetylcholine↗

PubMedDate not supplied

Conditioned taste aversion induced by toluene administration in rats.

Effect of toluene as unconditioned stimulus in the conditioned taste aversion (CTA) learning in rats was investigated for a behavioral assessment of toluene toxicity. Intraperitoneal (200-800 mg/kg B.W.) and intravenous (20-40 mg/kg B.W.) administration of toluene induced dose-dependent CTA. Inhalation exposure to toluene at 1650-3300 ppm for 4 hr also induced moderate CTA. These results suggest that toluene functions as a "behaviorally aversive" stimulus and that the required dose for the conditioning varies with the route of administration. In addition, the interference effect of toluene vapor odor on the taste stimulus, which would reduce the strength of CTA, was examined but not revealed.

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