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PubMed1995

Immunolocalization of putative neurotransmitters innervating autonomic regulating neurons (correction of neurones) of cat ventral medulla.

This study investigated possible sites of contact of nerve fibers containing a range of putative neurotransmitter substances onto neurons in the cat ventral medulla oblongata concerned with autonomic, particularly cardiovascular, regulation. The parasympathetic preganglionic neurons of the nucleus ambiguous (correction of ambiguus) were identified by retrograde horseradish peroxidase tracing from the vagus nerve, and the groups of neurons in the A1 and C1 cell areas and the raphe nucleus by catecholamine enzyme or 5-hydroxytryptamine (5-HT) immunohistochemistry, respectively. Immunoreactive (-ir)nerve fibers and terminals in the vicinity if these neurons were visualized by subjecting the sections to a dual-staining technique using a brown peroxidase-diaminobenzidine reaction product and a blue alkaline phosphatase-Fast blue reaction product. By employing monochrome photography with combinations of blue and orange-red filters, it was possible to discriminate neural elements displaying one or the other reaction product, or colocalization of reaction products. The results revealed the presence of calcitonin gene-related peptide (CGRP) and galanin (GAL)-ir in some motoneurons of the nucleus ambiguus, but not in those innervating the heart via the cardiac vagus nerve. The latter group of parasympathetic efferent neurons were found to be densely innervated by fibers immunoreactive for dopamine beta-hydroxylase (DBH, indicating noradrenaline), glycine (GLY), gamma-aminobutyric acid (GABA), 5-HT, enkephalin (ENK), neuropeptide Y (NPY), substance P (SP), and thyrotropin-releasing hormone (TRH), and, to a lesser extent, by other neuropeptide-ir fibers. The catecholamine cells of the rostral C1 and caudal A1 groups showed a broadly similar pattern of innervation, most noticeably by fibers immunoreactive for DBH, GABA, 5-HT, cholecystokinin (CCK), CGRP, ENK, GAL, NPY, and SP. The 5-HT-ir neurons of the raphe nucleus, some also containing SP, TRH, ENK, or corticotropin-releasing factor (CRF)-ir, were most prominently innervated by terminals containing DBH, GABA, CCK, ENK, NPY, TRH, somatostatin (SRIF), and vasoactive intestinal polypeptide (VIP)-ir. Although the proof that these groups of neurons receive functional synaptic contacts from the immunoreactive fibers awaits further ultrastructural studies, the results do suggest that a wide range of putative transmitters may influence the activity of efferent neurons in the cat medulla controlling autonomic functions.

Animals↗
PubMedDate not supplied

Nerve-sparing surgery with lateral node dissection for advanced lower rectal cancer.

133 patients who underwent nerve-sparing surgery with lateral dissection for lower rectal cancer were analysed for survival and functional results, operative burdens, and modes of recurrence. In 84% of patients an acceptable urinary function was preserved. Operative time averaged 334 min, and blood loss averaged 935 ml. The 5-year survival rate was 67% in all patients, and 88% for Dukes' A, 74% for Dukes' B and 59% for Dukes' C. According to the number of positive nodes, the 5-year survival rate comprised 83% of patients with up to three nodes, and 34% of those with more than four nodes. Local recurrent rates were 2.7% in patients with Dukes' B and 13% with Dukes' C. At present, pelvic nerve-sparing procedures with lateral dissection is the most promising surgery, guaranteeing both adequate lymphadenectomy and preservation of urinary function.

Autonomic Pathways↗
PubMed2006

Application of heat- and steam-generating sheets to the lumbar or abdominal region affects autonomic nerve activity.

Effects of applying a heat- and steam-generating (HSG) sheet on peripheral hemodynamics and autonomic nerve activity were examined. An HSG sheet was applied to the lumbar or abdominal region. Measurements included skin temperature at the lumbar and abdominal regions and the fingertip, total hemoglobin, tissue oxygen saturation ratio (StO2), pupillary light reflex, changes in ECG R-R interval blood pressure and percutaneous electrogastrography (EGG). A heat-generating sheet without steam was used as the control. Based on the present findings, application of the HSG sheet to the lumbar or abdominal region may improve peripheral hemodynamics and inhibit sympathetic nerve activity, resulting in parasympathetic nerve activity dominance.

Abdomen↗
PubMed2004

Discordant mental and physical efforts in an autistic patient.

We investigated whether there was mental effort in response to verbal commands in a 16-year old girl with autism, a high degree of non-compliance with commands and symptoms of autonomic dysfunction by monitoring the brainstem autonomic tone during an attempt to perform isometric exercise. An index of cardiac vagal tone (CVT), cardiac sensitivity to baroreflex (CSB), heart rate (HR) and mean arterial blood pressure (MAP) were measured simultaneously. Physical non-compliance with our commands meant there was no force applied by the patient during the attempted exercise, but CVT and CSB were both reduced and sustained at very low levels throughout the attempt, while MAP and HR were increased concurrently to higher levels in the same period. This vagal withdrawal to allow concurrent increases in HR and MAP is an arousal response appropriate for isometric exercise, which is a sign of a positive mental effort to comply with our commands. These results demonstrate discordant mental and physical efforts in our patient. In this particular case, the physical inabilities in some instances could have been mislabelled as mental non-compliance due to autism. It would be worthwhile to investigate the prevalence of discordant mental and physical efforts in autism.

Adolescent↗
PubMed2005

Reduced cardiac parasympathetic activity in children with autism.

Many of the clinical symptoms of autism suggest autonomic dysfunction. The aim of this study was to measure baseline cardiovascular autonomic function in children with autism using the NeuroScope, a device that can measure this brainstem function in real-time. Resting cardiac vagal tone (CVT), cardiac sensitivity to baroreflex (CSB), mean arterial blood pressure (MAP), diastolic blood pressure (DBP), systolic blood pressure (SBP) and heart rate (HR) were recorded in three different groups of children. The symptomatic group (n = 15) consisted of those with autism who exhibited symptoms or signs of autonomic dysfunction. The asymptomatic group (n = 13) consisted of children with autism but without symptoms or signs of autonomic dysfunction and the healthy children were in the control group (n = 17) [corrected]. The CVT and CSB were significantly lower in association with a significant elevation in HR, MAP and DBP in all children with autism compared with the healthy controls. Further more, the levels of CVT and CSB were lower in the symptomatic than in the asymptomatic group. The levels of CVT and CSB were not related to age in all the three groups. These results suggest that there is low baseline cardiac parasympathetic activity with evidence of elevated sympathetic tone in children with autism whether or not they have symptoms or signs of autonomic abnormalities.

Animals↗
PubMed2004

Single-unit activity of paraventricular nucleus neurons in response to intero- and exteroceptive stressors in conscious, freely moving rats.

Extracellular recordings of 114 neurons in the hypothalamic paraventricular nucleus (PVN) of conscious, freely moving male rats were performed using a movable electrode system. Single-unit activities were examined for their spontaneous firing patterns and responses to intero- and exteroceptive stressors, including disturbance in arterial blood pressure, water deprivation, air-jet stimulation, and systemic administration of cholecystokinin-8 (CCK). PVN neurons were assigned to one of two groups on the basis of their spontaneous firing patterns: phasic (n=29) and non-phasic (n=85). Intravenous (i.v.) administration of phenylephrine (8 microg/kg) resulted in the inhibition of a greater percentage of phasic-type (88.9%; 24/27) than non-phasic-type neurons (14.9%; 11/74). Most phasic-type neurons showed excitation in response to i.v. administration of sodium nitroprusside (20 microg/kg, 66.7%; 18/27) and water deprivation (15 h, 77.8%; 7/9) when compared to non-phasic-type neurons. Conversely, a greater number of non-phasic-type neurons showed excitation in response to air-jet stimulation (5 l/min, 10 s, 29.0%; 20/69) and to i.v. administration of CCK (5 microg/kg, 24.5%; 11/45) when compared to phasic-type neurons. However, most non-phasic-type neurons that demonstrated excitation in response to i.v. administration of CCK (88.9%; 8/9) did not respond to air-jet stimulation. The present study indicated that phasically firing neurons recorded from the PVN in conscious, freely moving rats are putative vasopressin-secreting neurons on the basis of their responses to intero- and exteroceptive stressors. These data contribute to our understanding of local neural mechanisms within the PVN that are responsible for stress responses in conscious rats.

Action Potentials↗
PubMed2004

Increased expression of neuronal nitric oxide synthase in bladder afferent cells in the lumbosacral dorsal root ganglia after chronic bladder outflow obstruction.

Nitric oxide (NO), a neurotransmitter in autonomic reflex pathways, plays a role in functional neuroregulation of the lower urinary tract. Upregulation of the levels of neuronal nitric oxide synthase (nNOS), the enzyme system responsible for NO synthesis, has been documented in the peripheral, spinal and supraspinal segments of the micturition reflex in diseases such as cystitis, bladder/sphincter dyssynergia following spinal cord injury and bladder overactivity after cerebral infarction. These observations suggest that NO might play a role in the development of bladder overactivity. In this study, nNOS-immunoreactivity (IR) was evaluated in bladder afferent and spinal neurons following bladder outflow obstruction (BOO) in male and female rats. Chronic BOO was induced by placing lumen reducing ligatures around the proximal urethra. Six weeks following the obstructive or sham surgery, bladder function was evaluated by awake cystometry. Bladder afferent neurons in L1, L2, L6 and S1 dorsal root ganglia (DRG) were identified by retrograde neuronal labeling with injection of Fast Blue into the bladder smooth muscle. A differential distribution of nNOS-IR was subsequently evaluated in bladder afferent neurons in the DRG and in the associated spinal cord segments. The percentage of bladder afferent neurons expressing nNOS-IR was increased in L6 (1.8-fold in males and 1.9-fold in females) and S1 (2.8-fold in males and 5.3-fold in females) DRG. In contrast, no changes in nNOS-IR in neurons or fiber distribution were observed in any spinal cord segments examined.

Animals↗
PubMed2004

Motor, sensory and autonomic nerve terminals containing NAP-22 immunoreactivity in the rat muscle.

Neuron-enriched acidic protein having a molecular mass of 22 kDa, NAP-22, is a Ca(2+)-dependent calmodulin-binding protein and is phosphorylated with protein kinase C (PKC). This protein is localized to the biological membrane via myristoylation and found in the membrane fraction of the brain and in the synaptic vesicle fraction. Recent studies showed that NAP-22 is localized in the membrane raft domain in a cholesterol-dependent manner and suggest a role for NAP-22 in maturation and/or maintenance of nerve terminals by controlling cholesterol-dependent membrane dynamics. The present study revealed the immunohistochemical distribution of NAP-22 in the peripheral nerves in rat muscles. In all examined muscles, nerve terminals in the motor endplates showed NAP-22 immunoreactivity associated with the membranes of synaptic vesicles and nerve terminals. In the muscle spindles, annulospiral endings, which made spirals around the intrafusal muscles, showed intense NAP-22 immunoreactivity. Autonomic nerve fibers around the intramuscular blood vessels also showed the immunoreactivity for NAP-22. NAP-22 immunoreactivity in these peripheral nerves was observed from birth to adulthood (100 days after birth). Though growth-associated protein-43 (GAP-43) immunoreactivity in these nerves was observed from birth, this immunoreactivity decreased from 20 days after birth. These findings suggest that NAP-22 is distributed and regulates functions in the motor, sensory and autonomic nerve terminals in the peripheral nervous system.

Animals↗
PubMed2005

Chronic administration of olmesartan attenuates the exaggerated pressor response to glutamate in the rostral ventrolateral medulla of SHR.

It has been shown that the pressor responses to microinjection of L-glutamate in the rostral ventrolateral medulla (RVLM) are augmented in spontaneously hypertensive rats (SHR), and that these augmented responses are not altered by chronic conventional antihypertensive treatment. The aim of the present study was to determine the effect of chronic oral treatment with a new angiotensin II type 1 (AT(1)) receptor antagonist, RNH-6270 (the active form of olmesartan medoxomil), on cardiovascular responses to excitatory amino acids in the RVLM of SHR. SHR (12 weeks old) were treated with RNH-6270 (30 mg/kg/day) or vehicle for 4 weeks. At 16 weeks of age, L-glutamate (2 nmol), N-methyl-D-aspartate (NMDA; an ionotropic glutamate receptor agonist (20 pmol)), or (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD; a metabotropic glutamate receptor agonist (1 nmol)) was microinjected into the RVLM of rats. The pressor responses to microinjection of L-glutamate or NMDA in the RNH-6270-treated SHR (+28.3 +/- 1.0 and +48.3 +/- 2.5 mm Hg, respectively) were significantly smaller than those in untreated SHR (+45.7 +/- 2.2 and +69.4 +/- 7.0 mm Hg, respectively, P < 0.05 each); however, they were still greater than those in the Wistar-Kyoto rats (+21.7 +/- 1.0 and +28.6 +/- 3.3 mm Hg, respectively, P < 0.05 each). In contrast, the augmented pressor responses to microinjection of (1S,3R)-ACPD in SHR were not affected by the RNH-6270 treatment. These results demonstrated that chronic oral treatment with RNH-6270, an AT(1) receptor antagonist, partly normalizes the pressor responses to L-glutamate or NMDA, but not (1S,3R)-ACPD, in the RVLM of SHR, suggesting that endogenous angiotensin II may be involved in the exaggerated pressor response to l-glutamate, probably through its ionotropic glutamate receptors.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2006

Ibotenic acid lesions reduce noradrenergic activation in ventromedial hypothalamus during hypoglycemia.

Noradrenergic and GABAergic systems in the ventromedial hypothalamus (VMH) are activated during hypoglycemia and initiate part of the compensatory counterregulatory response. Norepinephrine (NE) terminals innervating the VMH originate in glucosensing hindbrain areas, but whether NE activity in the VMH is under local control or in the hindbrain is unclear. To elucidate the role of neurons intrinsic to the VMH on NE release in the VMH during hypoglycemia, ibotenic acid (IBO), an NMDA receptor agonist that selectively destroys cell bodies, was used. In a 2 x 2 factorial study, IBO (3-5 microg/0.5 microL) or vehicle was stereotaxically administered into the VMH of male Sprague-Dawley rats. One week later, NE concentration in the VMH was measured by microdialysis during insulin-induced hypoglycemia (2.0 U/kg) or euglycemia (saline control). Baseline levels of NE were not statistically different (p=0.10) in IBO-treated compared with vehicle-treated rats (13.3+/-2.8 nM vs. 7.9+/-1.1 nM). The initial increase in interstitial NE concentration during hypoglycemia in control rats was absent in IBO-treated rats (p<0.01). In IBO-treated hypoglycemic rats, NE concentrations increased after 45 min to a similar level observed in control rats during the first 20 min of hypoglycemia. These results are consistent with the suggestion that local neurons in the VMH respond to hypoglycemia and modify NE activation in the VMH during hypoglycemia.

Animals↗
PubMed2006

Divergent projections of catecholaminergic neurons in the nucleus of the solitary tract to limbic forebrain and medullary autonomic brain regions.

The nucleus of the solitary tract (NTS) is a critical structure involved in coordinating autonomic and visceral activities. Previous independent studies have demonstrated efferent projections from the NTS to the nucleus paragigantocellularis (PGi) and the central nucleus of the amygdala (CNA) in rat brain. To further characterize the neural circuitry originating from the NTS with postsynaptic targets in the amygdala and medullary autonomic targets, distinct green or red fluorescent latex microspheres were injected into the PGi and the CNA, respectively, of the same rat. Thirty-micron thick tissue sections through the lower brainstem and forebrain were collected. Every fourth section through the NTS region was processed for immunocytochemical detection of tyrosine hydroxylase (TH), a marker of catecholaminergic neurons. Retrogradely labeled neurons from the PGi or CNA were distributed throughout the rostro-caudal segments of the NTS. However, the majority of neurons containing both retrograde tracers were distributed within the caudal third of the NTS. Cell counts revealed that approximately 27% of neurons projecting to the CNA in the NTS sent collateralized projections to the PGi while approximately 16% of neurons projecting to the PGi sent collateralized projections to the CNA. Interestingly, more than half of the PGi and CNA-projecting neurons in the NTS expressed TH immunoreactivity. These data indicate that catecholaminergic neurons in the NTS are poised to simultaneously coordinate activities in limbic and medullary autonomic brain regions.

Amygdala↗
PubMed2004

Progressive aging does not alter the interaction between autonomic cardiac activity and delta EEG power.

OBJECTIVE: We tested the hypothesis that the reductions of the changes in the respective influence of the cardiac sympathetic and vagal activity control and delta EEG activity with aging alter the interactions between the heart rate variability (HRV) and the delta sleep EEG power band. METHODS: A polysomnography was performed on 16 healthy young men and 19 healthy middle-aged men across the first 3 NREM-REM cycles. Spectral analysis was applied to electrocardiogram and electroencephalogram recordings. High Frequency (HF(nu)) of HRV as well as the maximum of cross-spectrum, coherency, gain and phase shifts between HF(nu) and delta sleep EEG power band were compared between both groups. RESULTS: Young men experienced more deep sleep than middle-aged men (P<0.001). In middle-aged subjects, HF(nu) was lower than the HF(nu) of their younger counterparts (P<0.001), but they showed similar increases during NREM sleep and similar decreases during REM sleep as the young subjects. Cross-spectrum values, coherency, gain and phase shifts between HF(nu) and delta were identical between the two groups. Modifications in HF(nu) show parallel changes and precede changes in delta EEG band by a similar leads of 11+/-6min in young men and 9+/-7 min in middle-aged men (P=0.23). CONCLUSIONS: Reduced changes in the respective influence of the cardiac sympathetic and vagal activity and delta EEG activity with progressive aging do not alter the relationship and phase difference between changes in the relative predominant cardiac vagal activity and delta power in middle-aged men. SIGNIFICANCE: Interaction between the cardiac sympathetic and vagal activity with delta EEG activity is maintained in middle-aged men.

Adolescent↗
PubMed2005

The physiological basis of reflexology and its use as a potential diagnostic tool.

Ill-health changes the anatomy and physiology of affected organs, some of which can be observed visually, elicited through physical examination or confirmed through biomedical analysis. Understanding how anatomical changes contribute to physiological signs and symptoms will help practitioners identify the pathology, appreciate its origin and development and justify prescribed interventions in a way which can be upheld by critical external scrutiny. Reflexology contributes to an holistic approach to care and has recently improved its credibility as a discipline which supports orthodox care. Several research publications have identified possible theories and principles for the mechanism of action of reflexology, but more research to explain its contribution in identifying ill-health and diseases, as well as appropriate treatment modalities, is needed. This paper explores the physiological basis of reflexology, some of the theories for the mechanism of action and its potential as a diagnostic tool.

Adult↗
PubMed2006

Sarin produces delayed cardiac and central autonomic changes.

The aim was to evaluate the acute and delayed effects of low dose sarin exposure on cardiac autonomic and brainstem catecholaminergic function in mice. The rationale was to expand our knowledge of the cardiovascular effects of this neurotoxic, acetylcholinesterase (AChE) inhibitor. C57BL/6 male mice with telemetric arterial catheters were injected with saline or sarin (8 microg/kg, 0.05x LD(50); sc, two injections) with blood pressure (BP) measurements made at 1 and 10 weeks after sarin exposure. BP and pulse interval variability (PI) and low and high frequency spectral oscillations were measured using autoregressive spectral analysis. In situ hybridization (ISH) was used to quantify tyrosine hydroxylase (TH) mRNA expression in brainstem cardiovascular centers. Sarin had no effect on blood AChE activity, heart rate (HR) or BP. There was a biphasic response in PI variance, an early increase (+140%) and a delayed decrease (-62%) at more than 2 months after sarin exposure. There were no changes in BP variance. Assuming that increased PI variance is a positive outcome, the short-term response to sarin should be protective. This is opposite for the delayed decrease in PI variance which is associated with adverse cardiovascular effects. There was an increase in TH mRNA in both locus coeruleus (0.18+/-0.05 vs. 1.4+/-0.2 microCi/g; control vs. sarin) and dorsal vagal complex (0.09+/-0.06 vs. 1.17+/-0.03 microCi/g; control vs. sarin). Results show that a dose of sarin which had no peripheral cholinergic effects caused changes in autonomic modulation, a short-term enhancement followed by a delayed impairment in heart rate variability. Sarin-induced cardiac effects suggest a controversial aspect to the use of pharmacological agents which target AChE for management of cardiovascular risk.

Animals↗
PubMed2003

Multipotentiality of the neural crest.

Multiple neural and non-neural cell types arise from the neural crest (NC) in vertebrate embryos. Recent work has provided evidence for multipotent stem cells and intermediate precursors in the early NC cell population as well as in various NC derivatives in embryos and even in adult. Advances have been made towards understanding how cytokines, regulatory genes and cell-cell interactions cooperate to control commitment and differentiation to pigment cells, glia and neurone subtypes. In addition, NC cell fates appeared to be unstable, as differentiated NC cells can reverse to multipotent precursors and transdifferentiate in vitro.

Animals↗
PubMed2005

Neurotrophins in murine viscera: a dynamic pattern from birth to adulthood.

There is growing evidence that target-derived neurotrophins regulate the function of visceral neurons after birth. However, the postnatal profile of neurotrophin supply from internal organs is poorly described. In this study, we compared neurotrophin concentrations in lysates of murine peripheral target tissues (lung, heart, liver, colon, spleen, thymus, kidney and urinary bladder) at different time points after birth. In most organs, there was a decrease of neurotrophin concentrations in the first weeks after birth. In contrast, there were characteristic increases of specific neurotrophins during adolescence or adulthood. These increases were found for nerve growth factor (NGF) in the heart, thymus, kidney and liver, for brain-derived neurotrophic factor (BDNF) in the lung, and for neurotrophin-3 (NT-3) in the colon. In conclusion, we show that neurotrophins display a very differential and dynamic profile in internal organs after birth.

Aging↗
PubMed2006

Autonomic innervation and segmental muscular disconnections at the human pulmonary vein-atrial junction: implications for catheter ablation of atrial-pulmonary vein junction.

OBJECTIVES: This study sought to examine the muscle connections and autonomic nerve distributions at the human pulmonary vein (PV)-left atrium (LA) junction. BACKGROUND: One approach to catheter ablation of atrial fibrillation (AF) is to isolate PV muscle sleeves from the LA. Elimination of vagal response further improves success rates. METHODS: We performed immunohistochemical staining on 192 circumferential venoatrial segments (32 veins) harvested from 8 autopsied human hearts using antibodies to tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT). RESULTS: Muscular discontinuities of widths 0.1 to 5.5 mm (1.1 +/- 1.0 mm) and abrupt 90 degrees changes in fiber orientation were found in 70 of 192 (36%) and 36 of 192 (19%) of PV-LA junctions, respectively. Although these anisotropic features were more common in the anterosuperior junction (p < 0.01), they were also present around the entire PV-LA junction. Autonomic nerve density was highest in the anterosuperior segments of both superior veins (p < 0.05 versus posteroinferior) and inferior segments of both inferior veins (p < 0.05 vs. superior), highest in the LA within 5 mm of the PV-LA junction (p < 0.01), and higher in the epicardium than endocardium (p < 0.01). Adrenergic and cholinergic nerves were highly co-located at tissue and cellular levels. A significant proportion (30%) of ganglion cells expressed dual adrenocholinergic phenotypes. CONCLUSIONS: Muscular discontinuities and abrupt fiber orientation changes are present in >50% of PV-LA segments, creating significant substrates for re-entry. Adrenergic and cholinergic nerves have highest densities within 5 mm of the PV-LA junction, but are highly co-located, indicating that it is impossible to selectively target either vagal or sympathetic nerves during ablation procedures.

Adult↗
PubMed2006

Neural-endocrine-immune complex in the central modulation of tumorigenesis: facts, assumptions, and hypotheses.

For the precise coordination of systemic functions, the nervous system uses a variety of peripherally and centrally localized receptors, which transmit information from internal and external environments to the central nervous system. Tight interconnections between the immune, nervous, and endocrine systems provide a base for monitoring and consequent modulation of immune system functions by the brain and vice versa. The immune system plays an important role in tumorigenesis. On the basis of rich interconnections between the immune, nervous and endocrine systems, the possibility that the brain may be informed about tumorigenesis is discussed in this review article. Moreover, the eventual modulation of tumorigenesis by central nervous system is also considered. Prospective consequences of the interactions between tumor and brain for diagnosis and therapy of cancer are emphasized.

Animals↗