Brain regions influenced by the lateral parabrachial nucleus in angiotensin II-induced water intake.

This study examined which brain regions are influenced by an inhibitory lateral parabrachial nucleus (LPBN) mechanism that affects water intake. Controls and rats with bilateral LPBN lesions were administered angiotensin II (AngII) (0.5mg/kg subcutaneous - SC), drinking responses measured, and brains processed for Fos-immunohistochemistry. A separate group of LPBN-lesioned and non-lesioned animals were denied water for 90 min prior to perfusion to remove any confounding factor of water intake. LPBN-lesioned rats drank a cumulative volume of 9 mL compared with <4 mL by controls (p<0.01). Compared with sham-lesioned animals, Fos expression was attenuated in overdrinking LPBN-lesioned rats in the median preoptic nucleus (MnPO), paraventricular nucleus of the hypothalamus (PVN), supraoptic nucleus (SON) (p<0.001), bed nucleus of the stria terminalis and central nucleus of the amygdala (p<0.01). In LPBN-lesioned rats that did not drink, greater numbers of activated neurons were detected in the PVN (p<0.001), SON (p<0.01), MnPO, nucleus of the solitary tract (NTS) and area postrema (p<0.05) in response to SC AngII, compared with non-lesioned rats. These data suggest that the direct effects of LPBN lesions caused an increase in AngII-induced water intake and in rats that did not drink an increase in Fos expression, while indirect secondary effects of LPBN lesions caused a reduction in Fos expression possibly related to excessive ingestion of water. An inhibitory mechanism, likely related to arterial baroreceptor stimulation, relayed by neurons located in the LPBN influences the responses of the MnPO, PVN and SON to increases in peripheral AngII.

Cardiovascular reactivity and neuronal activation to stress in Schlager genetically hypertensive mice.

Schlager inbred hypertensive mice (BPH/2J) have been suggested to have high blood pressure (BP) due to an overactive sympathetic nervous system (SNS). The brain nuclei associated with the hypertension are also those involved in the integration of the cardiovascular responses to stress. Therefore, in the present study, we hypothesize that BPH/2J mice likely have a greater response to stress that is associated with greater neuronal activation in the limbic system, hypothalamus and medulla in regions known to regulate sympathetic activity. Male hypertensive BPH/2J and normotensive BPN/3J mice were implanted with telemetry devices and exposed to dirty cage-switch, an acute model of aversive stress. Stress exposure caused a 60% greater pressor response in BPH/2J compared with BPN/3J mice and an increase in activity, by contrast the level of tachycardia was less in BPH/2J mice. Stress-induced cardiovascular responses were also associated with greater neuronal activation, as detected by c-Fos expression, in BPH/2J compared with BPN/3J mice in the medial nucleus of the amygdala (MeAm), dorsomedial hypothalamus (DMH) (P<0.001) and marginally in the rostral ventrolateral medulla (RVLM; P=0.7). These findings suggest that hypertension in the BPH/2J mice is associated with greater sympathetic vasomotor responses to central pathways mediating the arousal responses to acute aversive stress in particular the amygdala, hypothalamus and rostral ventrolateral medulla.

Lateral hypothalamic 'command neurons' with axonal projections to regions involved in both feeding and thermogenesis.

The concept of 'command neurons', whereby single neurons mediate complex and complementary motor functions to generate a stereotyped behaviour, is well developed in invertebrate physiology. The term has also been adopted more recently to explain the neural basis of 'fight or flight'. In this study we have investigated the possibility that single lateral hypothalamic neurons have the necessary neuroanatomical connections to coordinate two complementary limbs of body weight control, feeding and thermogenesis, thereby acting as 'command neurons'. The transynaptic retrograde transport of pseudorabies virus (Bartha) from a thermogenic endpoint in the brown adipose tissue of rats has been used in conjunction with other neuronal tracers, introduced into putative CNS feeding centres, to assess the potential for the involvement of command neurons in coordinating these processes. In discrete regions of the lateral hypothalamus, neurons have been identified which have the necessary complement of orexigenic peptides and collateral branching axons to both putative feeding sites and thermogenic sites in brown fat to qualify as candidate central command neurons controlling body weight.

The sensory circumventricular organs of the mammalian brain.

The brain's three sensory circumventricular organs, the subfornical organ, organum vasculosum of the lamina terminalis and the area postrema lack a blood brain barrier and are the only regions in the brain in which neurons are exposed to the chemical environment of the systemic circulation. Therefore they are ideally placed to monitor the changes in osmotic, ionic and hormonal composition of the blood. This book describes their. General structure and relationship to the cerebral ventricles Regional subdivisions Vasculature and barrier properties Neurons, glia and ependymal cells Receptors, neurotransmitters, neuropeptides and enzymes Neuroanatomical connections Functions.

Circulating relaxin acts on subfornical organ neurons to stimulate water drinking in the rat.

Relaxin, a peptide hormone secreted by the corpus luteum during pregnancy, exerts actions on reproductive tissues such as the pubic symphysis, uterus, and cervix. It may also influence body fluid balance by actions on the brain to stimulate thirst and vasopressin secretion. We mapped the sites in the brain that are activated by i.v. infusion of a dipsogenic dose of relaxin (25 microg/h) by immunohistochemically detecting Fos expression. Relaxin administration resulted in increased Fos expression in the subfornical organ (SFO), organum vasculosum of the lamina terminalis (OVLT), median preoptic nucleus, and magnocellular neurons in the supraoptic and paraventricular nuclei. Ablation of the SFO abolished relaxin-induced water drinking, but did not prevent increased Fos expression in the OVLT, supraoptic or paraventricular nuclei. Although ablation of the OVLT did not inhibit relaxin-induced drinking, it did cause a large reduction in Fos expression in the supraoptic nucleus and posterior magnocellular subdivision of the paraventricular nucleus. In vitro single-unit recording of electrical activity of neurons in isolated slices of the SFO showed that relaxin (10(-7) M) added to the perfusion medium caused marked and prolonged increase in neuronal activity. Most of these neurons also responded to 10(-7) M angiotensin II. The data indicate that blood-borne relaxin can directly stimulate neurons in the SFO to initiate water drinking. It is likely that circulating relaxin also stimulates neurons in the OVLT that influence vasopressin secretion. These two circumventricular organs that lack a blood-brain barrier may have regulatory influences on fluid balance during pregnancy in rats.

Efferent neural projections of angiotensin receptor (AT1) expressing neurones in the hypothalamic paraventricular nucleus of the rat.

Angiotensin II acts within the hypothalamic paraventricular nucleus (PVN) to help mediate a number of autonomic and endocrine responses. Evidence is sparse in regard to the particular neuronal cell groups that exhibit angiotensin II type 1 receptors within the PVN, and does not exist in relation to specified efferent neuronal populations in the nucleus. In the present experiments, retrogradely transported neuronal tracers were utilized in conjunction with immunohistochemistry using a well characterized polyclonal antibody raised against a decapeptide sequence at the carboxy terminus of the AT1 receptor, to determine whether it is preferentially distributed amongst different efferent populations within the PVN. The AT1 receptor is not associated with neurones in the PVN that project axons to the spinal cord, dorsomedial or ventrolateral medulla but coexists strongly with neurones in the anterior parvocellular division of the nucleus which direct axons to the median eminence. Such neurones often contain corticotropin releasing factor. These findings highlight the role that angiotensin II and AT1 receptors in the PVN may play in the mediation of responses to stress.

Fos immunoreactivity in the lamina terminalis of adrenalectomized rats and effects of angiotension II type 1 receptor blockade or deoxycorticosterone.

Neural activity, as measured immunohistochemically by the presence of Fos protein, was determined in the lamina terminalis, a thin strip of tissue forming the anterior wall of the third brain ventricle, after adrenalectomy. Several weeks after surgery, the adrenalectomized rats were maintained with access to water and a low sodium diet for five days. In addition, hypertonic (0.5M) NaCl solution was available for the entire five-day period (sodium available) or only during the first four days (sodium unavailable). The number of neurons expressing Fos, determined at the end of the fifth day, was increased in the adrenalectomized rats with or without NaCl solution to drink. Fos activity in the median preoptic nucleus was increased only in adrenalectomized rats without access to NaCl solution. Treatment of adrenalectomized rats with the sodium-retaining mineralocorticoid hormone, deoxycorticosterone, at the end of the fourth day, decreased Fos expression in the subfornical organ and the organum vasculosum of the lamina terminalis when NaCl solution was available but not when the NaCl solution was unavailable. In the adrenalectomized rats with NaCl solution available, mineralocorticoid treatment decreased both urinary sodium excretion and daily sodium intake. Brain nuclei in the lamina terminalis also became activated in intact rats made sodium deplete by treatment with the diuretic, furosemide. Relative to sodium-deplete intact rats, however, sodium-deplete adrenalectomized rats had a greater number of neurons expressing Fos in the organum vasculosum. Treatment of sodium-deplete rats, adrenalectomized or intact, with the angiotensin II-type 1 receptor antagonist, ZD7155, decreased sodium intake and Fos expression in the subfornical organ but not in the organum vasculosum of the lamina terminalis or median preoptic nucleus. In conclusion, the results demonstrated that activation of the brain nuclei located in the lamina terminalis of adrenalectomized rats was primarily related to sodium deficit and not to the absence of the mineralocorticoid hormones, although the adrenal hormones may have a role in limiting the activation of organum vasculosum of the lamina terminalis during sodium depletion. Furthermore, the results obtained with the administration of the angiotensin receptor antagonist are consistent with the proposal that sodium appetite of the sodium-deplete rat, adrenalectomized or intact, is mediated by circulating angiotensin II acting in the subfornical organ.

An anesthesia controlled substance dispensing system.

The problems associated with drug abuse or diversion by anesthesia personnel in the operating room (OR), causative factors, effective mechanisms of control of abusable drugs in this area of the hospital, and the need for these systems to be cost effective for the smaller hospital are discussed. A system utilizing anesthetist/case specific drug kits that are dispensed by the pharmacy to the OR and then to individual anesthetists is presented. The system limits quantities of drugs available at one time to anesthesia personnel and provides for clear individual accounting for drugs and the rapid detection and reconciliation of discrepancies. The system demands modest increases in personnel expense and capital and consumable equipment costs. The authors conclude that the system described may provide for improved abusable drug control in the OR at costs reasonable for the smaller hospital.