The brain is a target of environmental toxic pollutants that impair cerebral functions. Uranium is present in the environment as a result of natural deposits and release by human applications. The first part of this review describes the passage of uranium into the brain, and its effects on neurological functions and cognitive abilities. Very few human studies have looked at its cognitive effects. Experimental studies show that after exposure, uranium can reach the brain and lead to neurobehavioral impairments, including increased locomotor activity, perturbation of the sleep-wake cycle, decreased memory, and increased anxiety. The mechanisms underlying these neurobehavioral disturbances are not clearly understood. It is evident that there must be more than one toxic mechanism and that it might include different targets in the brain. In the second part, we therefore review the principal mechanisms that have been investigated in experimental models: imbalance of the anti/pro-oxidant system and neurochemical and neurophysiological pathways. Uranium effects are clearly specific according to brain area, dose, and time. Nonetheless, this review demonstrates the paucity of data about its effects on developmental processes and the need for more attention to the consequences of exposure during development.

A novel human Coronavirus (HCoV) was this year recognized as the etiological agent of the Severe Acute Respiratory Syndrome. Two other HCoV (HCoV-229E and HCoV-OC43) have been known for 30 years. HCoV-229E has been recently involved in nosocomial respiratory viral infections in high-risk children. However, their diagnosis is not routinely performed. Currently, reliable immunofluorescence and cell culture methodologies are not available. As part of a four-year epidemiological study in a Pediatric and Neonatal Intensive care unit, we have performed and demonstrated the reliability of a reverse transcription-PCR-hybridization assay to detect HCoV of the 229E antigenic group in 2028 clinical respiratory specimens. In hospitalized children (children and newborns) and staff members we found a high incidence of HcoV-229E infection. This reverse transcription-PCR-hybridization assay gave a high specificity and a sensitivity of 0.5 50% Tissue Culture Infective Dose per ml. This technique is reliable and its application for screening large number of clinical samples would improve the diagnosis of HCoVs respiratory infection and our knowledge of these viruses epidemiology.

Acetylcholinesterase (AChE) rapidly hydrolyzes acetylcholine. At the neuromuscular junction, AChE is mainly anchored in the extracellular matrix by the collagen Q, whereas in the brain, AChE is tethered by the proline-rich membrane anchor (PRiMA).The AChE-deficient mice, in which AChE has been deleted from all tissues, have severe handicaps. Surprisingly, PRiMA KO mice in which AChE is mostly eliminated from the brain show very few deficits. We now report that most of the changes observed in the brain of AChE-deficient mice, and in particular the high levels of ambient extracellular acetylcholine and the massive decrease of muscarinic receptors, are also observed in the brain of PRiMA KO. However, the two groups of mutants differ in their responses to AChE inhibitors. Since PRiMA-KO mice and AChE-deficient mice have similar low AChE concentrations in the brain but differ in the AChE content of the peripheral nervous system, these results suggest that peripheral nervous system AChE is a major target of AChE inhibitors, and that its absence in AChE-deficient mice is the main cause of the slow development and vulnerability of these mice. At the level of the brain, the adaptation to the absence of AChE is nearly complete.

SUMMARY The central cardiovascular effects of the calcium channel blocker nifedipine and the calcium channel activator BAY k 8644 were studied in anesthetized and ventilated normotensive Wistar-Kyoto (WKY) or spontaneously hypertensive rats (SHR). Both drugs were administered in a 1.5-/U.1 volume into the lateral ventricle of the brain (i.c.v.) or into the cisterna magna (i.e.). The injection of vehicle alone (i.e. or i.c.v.) did not significantly change mean arterial pressure (MAP) or heart rate. Nifedipine (5 and 50 /ug/kg) and BAY k 8644 (5 and SO fig/kg) induced opposite effects on MAP when centrally injected. Nifedipine decreased MAP and induced a bradycardia (i.c.v.) or no change in heart rate (i.e.), and BAY k 8644 increased MAP without any significant change in heart rate (i.e. or i.c.v.). These effects were more marked with the highest dose of either drug. These effects seemed to be of central origin, since they were suppressed by gang!ionic blockade by hexamethonium (100 mg/kg i.v.), whereas after hexamethonium the hypotensive and the hypertensive responses to intravenously injected nifedipine and BAY k 8644, respectively, were preserved. Bilateral vagotomy suppressed the bradycardia induced by i.c.v. administered nifedipine. Previously i.c.v. administered nifedipine (5 /u.g/kg) antagonized the pressor response to BAY k 8644 (5 jug/kg i.c.v.). Changes in MAP and heart rate were significantly more marked in SHR than in WKY. These results indicate that a calcium channel inhibitor and a calcium channel activator can modulate in opposite fashion central mechanisms involved in blood pressure control. (Hypertension 9: 132-138. 1987) KEY WORDS • 1,4-dihydropyridine • calcium channel blocker • spontaneously hypertensive rats • central nervous system • BAY k 8644 C ALCIUM channel blockers produce an in vitro direct depression of myocardial contractility and sinus node automaticity as well as relaxation of isolated coronary and peripheral blood vessels 1 ' 2 by inhibiting calcium influx into the cells. 3 The direct effects of calcium channel blockers on cardiovascular function can be modifed by their effects on the autonomic nervous system. 4 Calcium channel blockers have been reported to act peripherally to decrease neurotransmitter release at the neuromuscular junction 5 -6 and to modulate carotid baroreceptor function.7 Some evidence suggests that calcium channel blockers influence the autonomic nervous system at the central level, thus altering cardiovascular function.

Conduit arteries of hypertensive rats are thicker and stiffer than those of normotensive controls. The possible role played by collagen type I and II subtypes in the mechanism of arterial stiffness remains unknown. The carotid and aortic arterial wall of rats of Japanese (Wistar-Kyoto and spontaneously hypertensive rats) and Lyon (normotensive and hypertensive rats) origin were studied. The stiffness of the carotid wall material (ultrasound), the histomorphometry of the aortic wall with the content in collagen I and III subtypes and their corresponding mRNA were analyzed. Independently of hypertension, the Japanese group differed from the Lyon group by a stiffer carotid wall material at any given value of wall stress; a lesser degree of aortic hypertrophy with a higher percentage of elastin, and a higher density of collagen III but not of collagen I. All other hemodynamic and histomorphometric parameters were affected by both the origin of the rats (Japanese vs. Lyon) and the presence of hypertension. Large artery stiffness in genetically hypertensive rats was not only influenced by hypertension itself, but also by differences in the contents of collagen subtypes which are also found in their corresponding normotensive controls.

Under NO synthase inhibition, the vasoactive properties of Japanese and Lyon aorta differ in the presence of a cyclo-oxygenase blocker but not endothelin blockers. These results indicate that the aorta vasorelaxant tone is associated to prostanoid regulation in Lyon but not in Japanese rats. This observation appears dependent on the genetic and/or environmental background linked to the origin and not the presence of hypertension.

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