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PubMed2002

Quantitative assessment of the innervation of epineurial arteries in the peripheral nerve by immunofluorescence: differences between controls and patients with peripheral arterial disease.

The peripheral nerve is supplied by the vasa nervorum. The epi- and perineurial vessels are innervated by an autonomic plexus, which plays a role in regulation of the endoneurial blood flow. This innervation is decreased in diabetes and alcohol polyneuropathy and seems to precede the development of diabetic polyneuropathy. A decreased innervation may therefore play a role in the development of polyneuropathy. In peripheral arterial disease (PAD) clinical and morphological features are present, related to severity of ischemia. To investigate the innervation of the vasa nervorum in severe ischemia, we performed immunofluorescence staining with the general neural marker protein gene product (PGP) 9.5 in whole mount preparations of epineurial vessels of nine sural nerves taken from patients with legs amputated because of severe PAD (59+/-15 years, mean +/- SD) and ten age-matched controls (61+/-24 years). In patients with PAD the nerve density of the perivascular plexus was decreased in comparison with controls (mean intercept density/mm +/- SD) 26.0+/-6.9 in PAD and 39.9+/-10.7 in controls, area% 6.0+/-1.6 in PAD and 9.9+/-2.6 in controls, both P<0.01, t-test). A decreased perivascular plexus may result in a diminished regulation of the endoneurial blood flow in patients with severe PAD.

Adult↗
PubMed2005

Anatomical evidence for glutamatergic transmission in primary sensory neurons and onto postganglionic neurons controlling penile erection in rats: an ultrastructural study with neuronal tracing and immunocytochemistry.

In male rats, the dorsal penile nerve (DPN) conveys sensory information from the genitals to the lumbosacral spinal segments of the spinal cord. DPN is the afferent limb of a reflex loop that supports reflexive erections, and that includes a network of spinal interneurons and autonomic and somatic motoneurons to the penis and perineal striated muscles. Autonomic efferent pathways to the penis relay in the major pelvic ganglion (MPG). Glutamate (Glu) is a likely candidate as a neurotransmitter of reflexive erections. Both AMPA and NMDA glutamatergic receptor subunits are present in the lumbosacral spinal cord, and AMPA and NMDA receptor antagonists block reflexive erections. In the present study, we used tract-tracing experiments combined with immunohistochemical and immunocytochemical techniques to ascertain the presence of Glu at two different levels of the network controlling reflexive erections. DPN afferents were localized in the dorsal horn of the lumbosacral cord and displayed the characteristics of either C-fibers or Adelta fibers. DPN terminals (some of them glutamatergic) were mainly distributed in the medial edge of the dorsal horn in the L6 spinal segment. GluR1 subunits were present in some DPN afferents, suggesting that they could be autoreceptors. DPN fibers were also present in the MPG, as were Glu terminals and GluR4 subunits. The results reveal the presence of Glu in DPN fibers and terminals and suggest that both the spinal cord and the MPG use glutamatergic transmission to control reflexive erections.

Animals↗
PubMed2006

Autonomic dysfunction and impaired cerebral autoregulation in cirrhosis.

Cerebral blood flow autoregulation is lost in patients with severe liver cirrhosis. The cause of this is unknown. We determined whether autonomic dysfunction was related to impaired cerebral autoregulation in patients with cirrhosis. Fourteen patients with liver cirrhosis and 11 healthy volunteers were recruited. Autonomic function was assessed in response to deep breathing, head-up tilt and during 24-h Holter monitoring. Cerebral autoregulation was assessed by determining the change in mean cerebral blood flow velocity (MCAVm, transcranial Doppler) during an increase in blood pressure induced by norepinephrine infusion (NE). The severity of liver disease was assessed using the Child-Pugh scale (class A, mild; class B, moderate; class C, severe liver dysfunction).NE increased blood pressure similarly in the controls (27 (24-32) mmHg) and patients with the most severe liver cirrhosis (Child-Pugh C, 31 (26-44) mmHg, p=0.405 Mann-Whitney). However, the increase in MCAVm was greater in cirrhosis patients compared to the controls (Child-Pugh C, 26 (24-39) %; controls, 3 (-1.3 to 3) %; respectively, p=0.016, Mann-Whitney). HRV during deep breathing was reduced in the cirrhosis patients (Child-Pugh C, 6.0+/-2.0 bpm) compared to the controls (21.7+/-2.2 bpm, p=0.001, Tukey' test). Systolic blood pressure fell during head-up tilt only in patients with severe cirrhosis. Our results imply that cerebral autoregulation was impaired in the most severe cases of liver cirrhosis, and that those with impaired cerebral autoregulation also had severe parasympathetic and sympathetic autonomic dysfunction. Furthermore, the degree of liver dysfunction was associated with increasing severity of autonomic dysfunction. Although this association is not necessarily causal, we postulate that the loss of sympathetic innervation to the cerebral resistance vessels may contribute to the impairment of cerebral autoregulation in patients with end-stage liver disease.

Adult↗
PubMed2004

The efficacy of a nerve stimulator (CaverMap) to enhance autonomic nerve identification and confirm nerve preservation during total mesorectal excision.

PURPOSE: Sexual dysfunction after total mesorectal excision may be caused by injury to the autonomic nerves. During surgery, nerve identification is not always achieved, and, to date, there has been no method to objectively confirm nerve preservation. The aim of this study was to assess the efficacy of a nerve-stimulating device (CaverMap) to assist in the intraoperative identification of the autonomic nerves during total mesorectal excision, and objectively confirm nerve preservation after proctectomy is completed. PATIENTS AND METHODS: Sexually active consecutive male patients undergoing total mesorectal excision were prospectively enrolled in this study. During pelvic dissection, the surgeon attempted to localize the hypogastric and cavernous nerves. CaverMap was used to confirm these findings and to facilitate the identification in cases of uncertainty. At the completion of proctectomy, the nerves were restimulated to ensure preservation. Factors that could affect the surgeon's ability to localize the nerves and CaverMap to confirm this were evaluated. RESULTS: Twenty-nine male patients with a median age of 58 years were enrolled in this study. An attempt to visualize the hypogastric nerves during dissection was made in 26 patients; the surgeon was able to identify the nerves in 19 (73 percent) patients. CaverMap successfully identified the nerves in six of the seven remaining patients, and failed to identify them in only one case. An attempt to localize the cavernous nerves during dissection was made in 13 patients, of which localization was successful in 8 (61.5 percent) patients. CaverMap improved the identification rate in four of the remaining five patients. After proctectomy, CaverMap successfully confirmed the preservation of both hypogastric and cavernous nerves in 27 of 29 (93 percent) patients. A history of previous surgery statistically correlated with failure to identify the hypogastric nerves by the surgeon (P = 0.005). There were no adverse events related to use of the device. CONCLUSION: CaverMap may be a useful tool to facilitate identification of the pelvic autonomic nerves during total mesorectal excision and to objectively confirm nerve preservation.

Autonomic Pathways↗
PubMed2005

The efficacy of a nerve stimulator (Cavermap) to enhance autonomic nerve identification and confirm nerve preservation during total mesorectal excision.

PURPOSE: Sexual dysfunction after total mesorectal excision may be caused by injury to the autonomic nerves. During surgery, nerve identification is not always achieved, and, to date, there has been no method to objectively confirm nerve preservation. The aim of this study was to assess the efficacy of a nerve-stimulating device (CaverMap) to assist in the intraoperative identification of the autonomic nerves during total mesorectal excision, and objectively confirm nerve preservation after proctectomy is completed. PATIENTS AND METHODS: Sexually active consecutive male patients undergoing total mesorectal excision were prospectively enrolled in this study. During pelvic dissection, the surgeon attempted to localize the hypogastric and cavernous nerves. CaverMap was used to confirm these findings and to facilitate the identification in cases of uncertainty. At the completion of proctectomy, the nerves were restimulated to ensure preservation. Factors that could affect the surgeon's ability to localize the nerves and CaverMap to confirm this were evaluated. RESULTS: Twenty-nine male patients with a median age of 58 years were enrolled in this study. An attempt to visualize the hypogastric nerves during dissection was made in 26 patients; the surgeon was able to identify the nerves in 19 (73 percent) patients. CaverMap successfully identified the nerves in six of the seven remaining patients, and failed to identify them in only one case. An attempt to localize the cavernous nerves during dissection was made in 13 patients, of which localization was successful in 8 (61.5 percent) patients. CaverMap improved the identification rate in four of the remaining five patients. After proctectomy, CaverMap successfully confirmed the preservation of both hypogastric and cavernous nerves in 27 of 29 (93 percent) patients. A history of previous surgery statistically correlated with failure to identify the hypogastric nerves by the surgeon (P = 0.005). There were no adverse events related to use of the device. CONCLUSION: CaverMap may be a useful tool to facilitate identification of the pelvic autonomic nerves during total mesorectal excision and to objectively confirm nerve preservation.

Autonomic Pathways↗
PubMed2006

Operating behind Denonvilliers' fascia for reliable preservation of urogenital autonomic nerves in total mesorectal excision: a histologic study using cadaveric specimens, including a surgical experiment using fresh cadaveric models.

PURPOSE: Little is known about which urogenital nerves are liable to be injured along surgical planes in front of or behind Denonvilliers' fascia. METHODS AND RESULTS: Using semiserial histology for five fixed male pelves, we demonstrated that: 1) left/right communicating branches of bilateral pelvic plexuses run immediately in front of Denonvilliers' fascia; and 2) a lateral continuation of Denonvilliers' fascia separates the urogenital neurovascular bundle from the mesorectum. Notably, the mesorectum contains no or few extramural ganglion cells. At the level of the seminal vesicles, incision in front of Denonvilliers' fascia seems likely to injure superior parts of the pelvic plexus and the left/right communication. Moreover, at the prostate level, this incision misleads the surgical plane into the neurovascular bundle. Fresh cadaveric dissections of five unfixed male pelves confirmed that the surgical plane in front of Denonvilliers' fascia continues to a fascial space for the pelvic plexus containing ganglion cell clusters lateral and/or inferior to the seminal vesicles. CONCLUSIONS: To preserve all autonomic nerves for urogenital function, optimal total mesorectal excision for rectal cancer requires dissection behind Denonvilliers' fascia.

Aged↗
PubMed2007

Pulmonary vein encircling ablation alters the atrial electrophysiologic response to autonomic stimulation.

OBJECTIVE: Pulmonary vein encircling ablation is often effective in the treatment of atrial fibrillation (AF). The success of the procedure does not depend upon creation of continuous lines of block. Thus mechanisms by which pulmonary vein encircling can cure AF remain unclear. Stimulation of cardiac autonomic ganglia alters atrial refractoriness and potentiates AF. We hypothesized that pulmonary vein encircling alters atrial autonomic function and that these alterations account in part for prevention of AF recurrences following ablation. METHODS: Atrial effective refractory periods (ERP) and AF inducibility were quantified in ten dogs before and during central autonomic nerve stimulation. Pulmonary vein encircling ablation was then performed and electrophysiologic testing repeated. In two dogs subjected to sham procedures measurements were repeated without performance of ablation. Hearts were examined histologically. RESULTS: Autonomic nerve stimulation led to decreased atrial refractoriness and increased AF inducibility and duration. Each of these effects were attenuated following pulmonary vein encircling (e.g., mean ERP decreased before (-23.7 +/- 1.8, p < 0.001) but not after ablation (-2.3 +/- 1.9, p = 0.25); AF inducibility increased by 26% before vs. 5% after ablation). No attenuation was seen in the sham operated animals. Histologic analysis following pulmonary vein encircling demonstrated destruction of some but not all autonomic ganglia. CONCLUSION: Autonomic stimulation shortens atrial refractory periods and potentiates AF. Pulmonary vein encircling ablation partially destroys atrial autonomic inputs, attenuates the refractory period shortening effect of autonomic stimulation and decreases AF inducibility. Destruction of autonomic ganglia may contribute to the anti-fibrillatory effects of pulmonary vein encircling and warrants further investigation.

Adipose Tissue↗
PubMed2001

Migrainous features in cluster headache.

Migraine and cluster headache have been considered entirely separate clinical syndromes, both in routine clinical practice and in the 1988 International Headache Society classification. Neurologists seeing large numbers of patients soon realize, however, that there is a considerable overlap between the two conditions. Some patients have attacks with the cardinal features of cluster headache, but also have a few symptoms (especially a visual aura) usually attributed to migraine. In addition, it is not uncommon for a patient with a lifetime's history of migraine to experience a typical bout of cluster headache, although the reverse is less common. This article reviews the published series of such patients.

Autonomic Pathways↗
PubMed2004

Cluster headache mimics.

This article discusses cluster headache and a variety of cluster mimics, with the intention of aiding the practitioner in differentiating between primary cluster headache and secondary forms of cluster. Secondary causes of cluster headache include infections, tumors, vascular abnormalities, and head trauma. In addition, other trigeminal autonomic cephalgias occasionally can be difficult to distinguish from primary cluster headache.

Autonomic Pathways↗
PubMed1995

Role of peripheral autonomic neurones in maintaining adequate cardiac function.

This review has focused on the putative effects that peripheral autonomic neurones exert on cardiac myocytes. Through data obtained by the use of in situ and in vitro models, the unique synaptology and chemical sensitivities of the various types of neurones in intrinsic cardiac and extracardiac intrathoracic ganglia are becoming evident. The intrathoracic nervous system acts as a distributive network, processing in a complex fashion information that arises not only from cardiac, vascular and pulmonary tissues but also from extrathoracic tissues, to maintain adequate cardiac function. In challenging the current understanding of cardiac regulation, this view provides novel opportunities to develop pharmacological and surgical strategies to manipulate cardiac function in disease states.

Animals↗
PubMed1994

The inhibition of liver ornithine decarboxylase expression in neonatal rats by maternal separation or CNS beta-endorphin is independent of the pituitary.

Previously we have shown, in rat pups, that either short-term maternal separation (MS) or central (but not peripheral) administration of beta-endorphin (BE) markedly decreases basal levels of ornithine decarboxylase (ODC) activity throughout the body and suppresses liver ODC responsiveness to injected growth hormone (GH). In this study, hypophysectomized (hypox) pups were used to determine whether the pituitary mediates these effects. Hypophysectomy clearly did not prevent the inhibitory actions of MS or intracisternal (i.c.) BE on liver ODC gene expression. The inability of GH to stimulate ODC activity in hypox animals exposed to MS or given BE i.c. is not due to nutritional deprivation, as glucose supplementation did not reverse the response. The results from these studies demonstrate that the pituitary is not the conduit by which either MS or centrally-administered BE regulates liver ODC activity. Also, they support the hypothesis that BE or an analogous opioid neuropeptide is a prime organizer within the CNS of the adaptive physiological response of neonatal rats to short-term MS. As we have previously shown that autonomic neuronal pathways are not involved in the effects of MS on peripheral tissues, the data obtained suggest that increased activity of this CNS opioid system during MS triggers the release of "neurochemicals" into the bloodstream capable of suppressing growth in the mammalian neonate.

Adaptation, Physiological↗
PubMed1995

Fos-like immunoreactivity in vagal and hypoglossal nuclei in different feeding states: a quantitative study.

This study characterized the distribution of Fos-like immunoreactivity (FLI) in three hindbrain nuclei: dorsal motor nucleus of the vagus (DMN), nucleus of the solitary tract (NST) and hypoglossal nucleus (HG) in response to eating or activation of specific components of feeding behavior. The degree of FLI was quantified by automated image analysis software that provided an efficient and sensitive method for counting the number of cells labelled with Fos antibody. Ingestion, and anticipation, of a meal both increased FLI in the DMN and HG, but not in the NST. Sham feeding 1 M sucrose was a more potent stimulus for FLI activation in DMN and NST than combined oral plus gastric/postingestive stimulation provided by real feeding the same food. The results indicate that the physiological stimulus of eating is sufficient to elicit FLI in the hindbrain and that specific components of the feeding act, especially oral stimulation provided by sham feeding, can activate FLI. The results suggest further that, under specific experimental conditions, gastric and/or postgastric stimulation may decrease FLI in the NST and DMN.

Animals↗
PubMed1994

Are the cognitive-enhancing effects of nicotine in the rat with lesions to the forebrain cholinergic projection system mediated by an interaction with the noradrenergic system?

Experiments were conducted to test the hypothesis that the enhancing effect of nicotine on water maze performance in rats with lesions of the forebrain cholinergic projection systems (FCPS) is mediated by an interaction with the noradrenergic system, in particular the ascending dorsal noradrenergic bundle (DNAB) and its projection areas. Three groups of rats received lesions of either: i) the nucleus basalis (NBM) and medial septal area/diagonal band (MSA/DB) by infusion of alpha-amino-3-hydroxy-4-izoxazole propionic acid (AMPA) (FCPS group), ii) DNAB, by infusion of 6-hydroxydopamine (6-OHDA) (NOR group), or iii) both FCPS plus DNAB (COMB group). Control animals received vehicle. Choline acetyltransferase activity was reduced in the cortex and hippocampus of the FCPS and COMB groups and in the hippocampus of the NOR group. NA level was reduced in the cortex and hippocampus of the FCPS and COMB groups, but not the FCPS group. In a reference memory task, the performance of both the NOR and COMB groups, but not the NOR group, was significantly worse than that of controls; there was no effect of nicotine administration (0.1 mg/kg) on escape latency or other measures in this task. In a working memory task, FCPS and COMB rats took longer to find the submerged platform on the second and following trials, and there was a significant enhancement of performance by nicotine in both groups, but not in controls. These results indicate that the enhancing effects of nicotine in rats with FCPS lesions are not mediated by an interaction with the DNAB.

Animals↗
PubMed1994

Effects of intraseptally injected glutamatergic drugs on hippocampal sodium-dependent high-affinity choline uptake in "naive" and "trained" mice.

We have previously reported that spatial reference memory (RM) training-induced alterations in hippocampal cholinergic activity as measured by sodium-dependent high-affinity choline uptake (SDHACU). Each training session was found to induce an immediate (30 s) increase in SDHACU followed (30 s to 15 min posttest) by a deactivation and long-lasting inhibition (15 min to 24 h) of this cholinergic marker. The present experiments were designed to assess the role of septal glutamatergic receptors in this posttraining cholinergic deactivation. In the first experiment, the effects of intraseptal injections of different doses of glutamic acid and glutamatergic antagonists (kynurenic acid, KYN, and AP5) on hippocampal SDHACU were studied in awake but otherwise resting (i.e., naive) mice. The results showed that glutamic acid at the lowest dose used (5 ng) produced a decrease in SDHACU, whereas both glutamatergic antagonists produced a dose-related increase in this cholinergic marker. It was concluded that septal glutamatergic receptors mediate a tonic inhibitory input on the cholinergic cells. Hence, in a second experiment the effect of intraseptal injections of KYN (5 ng) on the training-induced changes in hippocampal cholinergic activity were assessed following variable amounts of radial maze RM training. Trained mice were injected 20 min before the first or the ninth training session and killed 30 s or 15 min posttraining for determination of SDHACU. KYN slowed the posttesting cholinergic deactivation (disinhibition), this effect being more marked in good learners than in bad learners. The present findings suggest that septal glutamatergic receptors mediate an inhibitory input on the cholinergic cells, and that this input could play a role in memory consolidation.

Animals↗
PubMed1994

Fear-potentiated startle elevates catecholamine levels in the dorsomedial hypothalamus of rats.

The norepinephrine (NE), dopamine (DA), and serotonin (5-HT) systems are thought to be important in the development of anxiety and stress. The dorsomedial hypothalamus (DMH) of rats has been implicated in the regulation of physiological and behavioral responses associated with fear and anxiety. In order to elucidate the interactions between the monoamine systems and the DMH, we studied the effects of subjecting rats to the fear-potentiated startle test, a commonly used test of anxiety in rats, on the NE, DA, and 5-HT levels in the DMH. Rats in the potentiated startle test, but not those exposed to just foot shocks or acoustic startle, showed significantly higher levels of NE and DA in the DMH compared to cage controls. In contrast, foot shocks significantly elevated the 5-HT levels in the DMH.

Animals↗
PubMed1992

Light enhances sympathetic and suppresses vagal outflows and lesions including the suprachiasmatic nucleus eliminate these changes in rats.

Neurons in the suprachiasmatic nucleus (SCN) are suggested to be involved in the mechanism of glucose homeostasis. This mechanism was examined by studies on the effect of illumination on the activity of autonomic efferents to the adrenals, pancreas and liver. Exposure of one eye of anesthetized rats to light enhanced the efferent activity of the adrenal nerve and suppressed that of vagal pancreatic and hepatic nerves. No change in efferent activities of these nerves was observed on light-stimulation of rats with lesions that included the bilateral SCN. These findings indicate that light signals modulate visceral functions including metabolic processes through the retinohypothalamic tract probably via the SCN to autonomic efferent pathways innervating visceral organs.

Adrenal Glands↗
PubMed1995

Sympathetic and afferent neurones projecting into forelimb and trunk nerves and the anatomical organization of the thoracic sympathetic outflow of the rat.

The anatomy of the cervicothoracic sympathetic nerves was studied in the rat. Details of the arrangements of white and grey rami communicantes and superior cervical, middle cervical and stellate ganglia are given. Dorsal root and sympathetic ganglion neurones projecting to skin and muscle of the forelimb and trunk were labelled retrogradely with horseradish peroxidase (HRP) in order to study their number, segmental distribution and location. HRP was applied to forelimb nerves supplying skeletal muscles (Ramus profundus of radial nerve, RP) or hairy skin (N. cutaneus brachii lateralis superior of axillary nerve, CB), to mixed nerves (median nerve, ME; ulnar nerve, UL; radial nerve, RA) and to segmental thoracic nerves supplying hairy skin of the back (dorsal cutaneous nerve, CD) and to mixed internal intercostal nerves (IC). All sensory and sympathetic neurones were located ipsilaterally. In the forelimb nerves sensory somata were commonly restricted to two or three adjacent dorsal root ganglia (usually C6-7 for CB; C7-8 for ME; C7-Th1 for RA and RP; C8-Th1 for UL). Nearly all of the sympathetic somata were located in the middle cervical and stellate ganglia (fusion of C6-Th3). Some 0-0.4% lay in Th4 and Th5, none in the superior cervical ganglia. In the trunk nerves sensory somata were strictly segmentally organized. Sympathetic somata were distributed more widely over 4-5 segments with 50-55% in the segmental ganglion and up to 41% in the next caudal segment. From the data, it is estimated that 400 sympathetic (28%) and 1050 afferent neurones project into CB, 1660 (29%) and 4050 into RA, 540 (42%) and 760 into RP, 1010 (22%) and 3670 into ME, 880 (22%) and 3040 into UL, 350 (25%) and 1040 into IC and 500 (27%) and 1370 into CD.

Animals↗