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Neurogenic hypertension after depletion of norepinephrine in anterior hypothalamus induced by 6-hydroxydopamine administration into the ventral pons: role of serotonin.

Destruction of the ventral noradrenergic pathway elicited by administration of 6-hydroxydopamine (6-OHDA, 5 micrograms into each side of the ventral pons) reduced the content of norepinephrine (NE) in the anterior hypothalamus (-80%) and induced an increase in arterial blood pressure (ABP) and in heart rate. These hypertensive rats, showed hypersensitivity to the hypotensive effect of NE (0.5-2 micrograms) and clonidine (0.75-1.5 micrograms) administered into the anterior hypothalamic preoptic (AH/PO) region. Methysergide (1-2 micrograms) and, to a lesser extent, ketanserin (1-2 micrograms) administered into the anterior hypothalamic preoptic region also reduced the arterial blood pressure in these rats treated with 6-OHDA. Bilateral administration of 5,7-dihydroxytryptamine (5,7-DHT, 8 micrograms) into the median forebrain bundle decreased the content of serotonin (5-HT) in the hypothalamus (-85%) without change in arterial blood pressure but largely prevented the development of hypertension after treatment with 6-OHDA in the ventral pons. These results suggest that neurogenic hypertension is produced after the removal of NE tonic depressor activity in the anterior hypothalamus and that serotonergic mechanisms play a major role in the development of the increased arterial blood pressure in this preparation.

5,7-Dihydroxytryptamine↗

Successful removal of cryptic arteriovenous malformation located at the upper ventral pons via subtemporal transtentorial approach.

BACKGROUND: Lesions located at the ventral portion of the brain stem are still difficult to access surgically. We report herein a case of ventral pontine cryptic arteriovenous malformation that was successfully removed via a subtemporal-transtentorial approach. CASE REPORT: An 18-year-old female patient experienced repetitive hemorrhagic attacks leading to a massive pontine hemorrhage with several neurologic deficits. Since angiography and magnetic resonance imaging failed to delineate the hemorrhagic origin, a combination of multiple approaches was initially attempted. The subtemporal-transtentorial approach made it possible to obtain an adequate operative view in this case. An angioma observed at the septum of the multilocular hematoma was totally removed. Pathologic examination of the resected specimen revealed it to be an arteriovenous malformation. Postoperatively, the patient showed unexpectedly good recovery despite the original massive pontine hemorrhage. CONCLUSIONS: Several surgical approaches to the ventral pons have been proposed in the literature. While the subtemporal-transtentorial approach was useful in our patient, multiple routes should be considered to access a massive lesion of unknown extent at the ventral pons. The unexpected recovery observed in our patient suggests that surgery is an option in the treatment of this type of lesion.

Adolescent↗

Glycine produced pressor responses when microinjected in the pressor areas of pons and medulla in cats.

In 24 cats under chloralose/urethane anesthesia changes of systemic arterial pressure (SAP) and sympathetic vertebral nerve activities (VNA) were induced by microinjection of glycine (Gly, 1.0 M, 50 nl) into the pressor areas of the rostral pons, i.e., locus coeruleus-parabrachial nucleus (LC-PBN), nucleus of gigantocellular tegmental field-lateral tegmental field (FTG-FTL), and dorsomedial (DM) and ventrolateral (VLM) medulla. The effects were compared with those induced by microinjection of sodium glutamate (Glu, 0.25 M, 50 nl) into the same sites. In about 60% of the injections Gly produced increases in SAP and VNA similar to that of Glu. The increase in SAP was greater in VLM, while the increase in VNA was more marked in DM. In the rest of microinjections Gly and Glu produced changes of SAP and VNA in different combinations. The latency of Gly-induced increases in SAP and VNA was 1 to 3 s longer than that induced by Glu. Our findings show that although Gly is classified as an inhibitory transmitter, it often produced excitation of the pressor neurons in the pons and medulla similar to that of Glu. Whether Gly acts through the same cardiovascular neurons that respond to Glu or through activation of different kinds of neurons remains to be elucidated.

Animals↗

Visualization of G(o)alpha subtype guanine nucleotide-binding regulatory protein in the medulla oblongata and pons of the rat.

This study reports on the visualization of G(o) protein in the medulla oblongata and pons of Sprague-Dawley rats, using a commercially available selective polyclonal antiserum against a 39-kDa protein corresponding to the alpha subunit of G(o). Specific immunofluorescent-staining was widely distributed in neuropils and neuronal cell bodies but displayed regional heterogeneity. The immunoreactive product exhibited a punctate appearance and was most pronounced in the cell membrane and cytoplasm of the perikarya and proximal dendrites whereas the nucleus remained unstained. Positive immunoreactivity of G(o)alpha was present in nucleus reticularis gigantocellularis, nucleus reticularis paramedialis, nucleus tractus solitarii, nucleus nervi hypoglossi, nucleus raphé pallidus, locus coeruleus, nucleus tractus mesencephali nervi trigemini and nucleus cuneatus. These results provided anatomic evidence to support the participation of G(o) protein in both sensory and motor functions that originate from the medulla oblongata and pons of the rat.

Animals↗

An HRP study of the brainstem afferents to the accessory abducens region and dorsolateral pons in rabbit: implications for the conditioned nictitating membrane response.

Brain projections to the accessory abducens region and dorsolateral pons were investigated in rabbit using implants of crystalline horseradish peroxidase (HRP). Following implantation of HRP in the accessory abducens region (N = 3), labeled cells were observed in the sensory trigeminal nuclei and other regions implicated in the reflex pathway of the defensive nictitating membrane (NM) response. Neurons in the supratrigeminal zone were also labeled, as were portions of the contralateral red nucleus. Implantation of HRP into the dorsolateral pons (N = 5) revealed ipsilateral projections from deep-cerebellar nuclei in some cases. In addition, the parvocellular reticular formation displayed bilateral labeling of cells and an ipsilateral network of fibers and apparent terminations. Many cells of the contralateral supratrigeminal zone were labeled in these cases. Results were discussed in relation to lesioning and electrophysiological studies implicating the supratrigeminal region and other structures in the control of the classically conditioned NM response. Specifically, the possibility that supratrigeminal neurons are premotor elements responsible for the conditioned response is considered. Alternative hypotheses are discussed, including pathways by which cerebellar nuclei could control conditioned responding.

Abducens Nerve↗

Effect of alpha1-adrenergic receptor antagonist on the noradrenaline-induced facilitation in respiratory rhythm in newborn rat pons-medulla-spinal cord preparations.

We hypothesized that facilitation of respiratory rhythm by noradrenaline (NA) in rat pons-medulla-spinal cord preparations is mediated through alpha1-adrenergic receptors. In 0- to 4-day-old rats, the respiratory frequency (fR) was monitored at the C4 ventral root and trigeminal motor (VMO) outputs. fR at temperature (Te)=23 degrees C was lower than that at a higher Te (27 degrees C) and was increased by NA. At 23 degrees C, lower concentrations of NA were needed to produce the same increases in fR seen at 27 degrees C. With highest NA concentration we tested (50 microM), activity at C4 was maintained in all preparations at both Te, whereas that at VMO was maintained in 50% (27 degrees C) or 88% (23 degrees C) of the preparations. Particularly, tonic activity at C4 appeared in all preparations at both Te, but that at the VMO occurred in 0% (27 degrees C) or 18% (23 degrees C) of the preparations. Based on these results, we used the lower Te (23 degrees C) and applied a low concentration of NA (3 microM) to the preparations. We found that: (1) with the addition of NA, fR was increased without the occurrence of tonic activity and (2) NA-related fR facilitation was inhibited by pre-treatment with the alpha1-adrenergic receptor antagonist prazosin (2 microM). fR was increased by application of the alpha1-adrenergic receptor agonist phenylephrine (4 microM), and this response was inhibited by prazosin (4 microM). At Te=23 degrees C, fR facilitation by NA in newborn rat pons-medulla-spinal cord preparations was obtained by activation of alpha1-adrenergic receptors.

Adrenergic alpha-1 Receptor Agonists↗

Distribution and medullary projection of respiratory neurons in the dorsolateral pons of the rat.

The dorsolateral pons around the parabrachial nucleus including the Kölliker-Fuse nucleus is closely linked with the medullary respiratory center and plays an important role in respiratory control. We aimed to elucidate the firing properties, detailed distributions, and medullary projections of pontine respiratory neurons in pentobarbitone-anesthetized, paralyzed, and artificially ventilated rats with intact vagi. A total of 235 respiratory neurons were recorded from the dorsolateral pons in and around the Kölliker-Fuse nucleus. Six types of firing patterns were identified: inspiratory, expiratory-inspiratory phase spanning, inspiratory-expiratory phase spanning, decrementing expiratory, augmenting expiratory, and whole-phase expiratory patterns. Of these, the inspiratory neurons and the expiratory-inspiratory phase spanning neurons, which constituted the largest population (61%), were characterized most carefully by changing lung inflation levels, since under some conditions both showed similar firing patterns. Many (58%) of the 133 respiratory neurons examined were antidromically activated by electrical stimulation of the medulla. They were activated from the ventrolateral medulla around the ventral respiratory group and the Bötzinger complex and from the dorsomedial medulla around the nucleus tractus solitarii and the hypoglossal nucleus. The projections to the dorsomedial medulla were bilateral in many cases, and those to the ventrolateral medulla were unilateral. Of these medullary projections, two specific projections could be characterized in detail. First, many expiratory-inspiratory phase spanning neurons projected to the hypoglossal nucleus, suggesting that these pontine neurons are important premotor neurons of the hypoglossal motoneurons. This projection explains well the hypoglossal inspiratory activity, which is often dissociated from the phrenic inspiratory activity. Second, most whole-phase expiratory neurons that were distributed medially to the KF nucleus sent their axons toward the spinal cord via the midline medulla. These findings provide a new insight into the pontine control of medullary and spinal respiratory function.

Action Potentials↗

Epidermoid tumor of the pons.

Epidermoid tumors originating from the brainstem are extremely rare. The authors report a patient with an intraaxial epidermoid tumor of the pons. The tumor involved most of the pons and had a small exophytic component.

Adult↗

Sleep modulates cannabinoid receptor 1 expression in the pons of rats.

Endocannabinoids seem to play a role in the modulation of alertness. Therefore, we measured cannabinoid receptor 1 (CB1R) protein by Western blot and messenger RNA (mRNA) by reverse transcription-polymerase chain reaction in the pons of rats across the 24-h period. We performed evaluations every 4 h beginning at 09:00 h. Rats were under a controlled light/dark cycle 12:12 (lights on at 08:00 h). Our data suggest that the expression of CB1R gene depends on diurnal variations, with maximum expression at 13:00 h for protein and 21:00 h for mRNA, and minimum expression at 01:00 and 09:00 h, respectively. We also analyzed CB1R protein and mRNA levels in the pons of rats deprived of total sleep for 24 h and in rats with a 24-h period of sleep deprivation plus a 2-h period of sleep rebound. Unlike sleep deprivation, sleep rebound significantly increased CB1R protein while decreasing mRNA. Despite the fact that we used gentle manipulation to deprive the animals of sleep, there may be a potential influence of stress on this effect, too. However, these facts suggest that CB1R gene expression is modulated by the light/dark cycle and by sleep.

Animals↗

Excitability level-setting mechanisms in the pons: their behavioral support in decerebrate, reflex standing and freely moving, intact cats.

In the acute precollicular-postmammillary decerebrate cat, stimulation of the mesencephalic locomotor region (MLR) induces "controlled locomotion" on a moving treadmill. Stimulation of the dorsal area and of the ventral area of the pons at its midline elicited a long-lasting decrease and an increase in the tone of the hindlimb extensor muscles, respectively. By selecting the stimulus strength according to the stimulus site, it was possible to set the extensor muscle tone level, that is the "background excitability" of the brain stem and the spinal cord. Locomotor effects induced by MLR stimulation were greatly modified by the set level of background excitability. When the background excitability was high, MLR stimulation evoked "spastic" locomotor movement, while "atonic" locomotor movement was evoked when it was low. Furthermore, stimulation of the ventral area alone also evoked "spastic" locomotor movement. During locomotion in intact cats, stimulation of the dorsal area evoked a series of postural changes. Within a few seconds from the beginning of stimulation, the cat ceased to walk, but maintained a standing posture with or without a locomotor figure. With continuation of this stimulation, it squatted and then lay down on the floor in a sequential manner. Stimulation of the ventral area of the pons evoked an almost opposite series of postural changes. Within a few seconds from the beginning of stimulation, the cat changed from a lying to a squatting posture, and then stood, started to walk and continued to walk during the period of stimulation. All these results demonstrate that an increase in extensor muscle tone and activation of the spinal stepping generator are not separate phenomena, and suggest that integration of neuronal mechanisms involved in the setting of the background excitability and in locomotor movement is a prerequisite for successful expression of locomotor behavior both in decerebrate and intact cats.

Animals↗

Imaging the trigeminal nerve and pons before and after surgical intervention for trigeminal neuralgia.

OBJECTIVE: To study the various imaging changes occurring in the trigeminal nerve and brainstem in patients before or after trigeminal neuralgia surgery. METHODS: During a 7-year period, 275 patients with trigeminal neuralgia underwent high-resolution, contrast-enhanced magnetic resonance imaging (MRI) of the pons during gamma knife radiosurgery. Ninety-seven patients had no previous surgical intervention for trigeminal neuralgia, and 178 patients had undergone one or more previous procedures. Two independent observers, one of whom was blinded to patients' clinical details, reviewed MRI scans retrospectively. The analysis of the independent observers was then correlated with all previous therapeutic interventions. RESULTS: One hundred one MRI scans demonstrated no radiological changes related to trigeminal neuralgia, and 174 MRI scans exhibited some radiological abnormality. The average axial plane diameter of the nerve for all patients was 4 mm (range, 2-6 mm). In the group that had not undergone previous surgery, 65 patients (67%) exhibited vascular compression. In the 88 patients who had undergone previous microvascular decompression, 21 (24%) had evidence of a pontine infarction. Twenty-six patients experienced facial sensory loss, 22 (88%) of whom had undergone previous surgery with evidence of a pontine infarction (n = 11) or perineural scarring (n = 6). CONCLUSION: The majority of patients who had undergone previous trigeminal neuralgia surgery demonstrated readily identifiable abnormalities of the trigeminal nerve or brainstem. The frequency of such changes correlated with the type and number of procedures. Evidence of vascular compression was detected in the majority of patients. Most patients with postoperative facial sensory loss demonstrate changes in the nerve or pons on MR images.

Adult↗

Cholinergic stimulation of the pons depresses respiration in decerebrate cats.

The injection of carbachol into the pontine tegmentum of decerebrate cats evokes a postural motor atonia that has many of the characteristics of the atonia of natural rapid-eye-movement (REM) sleep (Morales et al. J. Neurophysiol. 57: 1118-1129, 1987). We have used the carbachol-injected decerebrate cat to study the changes in respiratory neuronal activity that accompany the atonia. The activities of representative respiratory motor nerves--phrenic, intercostal, and hypoglossal--and that of a motor branch of C4 were recorded in decerebrate, vagotomized, paralyzed, and artificially ventilated cats. After the microinjection of carbachol, there was a profound suppression of activity in all the nerves and a decrease in respiratory rate. This was a consistent stereotyped response in which the magnitude of the suppression of respiratory-related activity was phrenic (to approximately 65% of control) less than inspiratory intercostal (approximately 50%) less than hypoglossal (approximately 10%) less than expiratory intercostal (approximately 5%). The decrease in respiratory rate (to approximately 70% of control) was caused by a prolongation of both inspiratory and expiratory durations. Complete reversal of the carbachol effect was elicited by the microinjection of atropine into the same site as the carbachol injection. This allowed us to produce a second episode of atonia by the injection of carbachol into the contralateral pons. Thus we have demonstrated the existence of neural pathways originating in the cholinoceptive cells of the pons that have the potential to powerfully and differentially depress various respiratory motoneuronal pools and to reduce the respiratory rate. These pathways are likely to be activated along with the atonia of REM sleep.

Animals↗

Ganglioside patterns mature at different rates in functionally related subregions of the rat pons.

Gangliosides are known to be developmentally regulated and regionally variable, but these variations have not been shown to occur among precisely defined nuclei of the brain in relation to either aging or function. We have sought to correlate changes in ganglioside distribution with age-related changes in highly specific brain regions known to control a common function, the regulation of rapid eye movement sleep architecture. Gangliosides were extracted and quantified from micropunched regions of the locus coeruleus, dorsal raphe, laterodorsal tegmentum, pedunculopontine tegmentum and the general region of the pons containing these nuclei in young adult (3 months), adult (12 months), and aged (24 months) rats. The ganglioside distribution patterns were generally characteristic of the pons as a whole, but showed a high level of differentiation in time course at specific anatomical sites.

Aging↗

Effects of chronic treatment with phenazone on the hot-plate test and [3H]serotonin binding sites in pons and cortex membranes of the rat.

Many reports indicate that nonsteroidal anti-inflammatory drugs exert their antinociceptive effect through adrenergic and serotoninergic systems. We investigated the acute and chronic effects of phenazone on the pain threshold and on brain serotonin binding sites. A relationship between phenazone serum levels and the antinociceptive effect was found; acute treatment with phenazone provokes a significant decrease in serotonin binding sites both in the pons and cerebral cortex after 2, 4 and 8 h, but not after 24 h. After 15 and 30 days of treatment, the number of binding sites increases both in the pons and cortex.

Animals↗

Immunocytochemical development of transferrin and ferritin immunoreactivity in the human pons and cerebellum.

The distribution and development of transferrin-positive cells in the pons and cerebellum of human fetuses to adults were examined immunohistochemically, compared with those of ferritin-positive cells. Transferrin was present in oligodendrocytes, astrocytes, and neurons. Transferrin-positive neurons appeared at 18 weeks of gestation in Purkinje cells and the pontine reticular formation. In the pontine nuclei, transferrin-positive neurons appeared at 22 weeks of gestation. On the other hand, transferrin-positive glia also appeared at 18 weeks of gestation in the reticular formation, and at 24 weeks of gestation in the cerebellar white matter and pontine nuclei. Transferrin-positive glia and cells appeared earlier in the reticular formation of the pons than ferritin, but the order of its appearance was similar to that of ferritin and myelination. Because iron is involved in the syntheses and functions of dopamine, serotonin, and gamma-aminobutyric acid (GABA), transferrin may be carried for various iron uses from an early fetal stage.

Adult↗

Electrolytic lesions of the dorsal rostral pons prevent adrenocorticotropin increases after hemorrhage.

To determine if a discrete area of the dorsal rostral pons in the region of the locus coeruleus (LC) is essential for the reflex response of ACTH to hemorrhage, chloralose-anesthetized cats with bilateral electrolytic (11 cats) or sham (3 cats) lesions were challenged with a 15 ml/kg X 3 min hemorrhage. Sequential arterial blood samples taken at -6, -3, 3, 6, 9, 15, and 21 min from hemorrhage were analyzed for ACTH content. Cats were grouped according to whether plasma ACTH increased in response to hemorrhage. Bilateral lesions in 7 cats with an area in common, which lay within the LC complex, blocked the reflex increase in plasma ACTH in response to hemorrhage which was seen in 3 sham-lesioned cats, in 3 cats with lesions that did not infringe in this region bilaterally, and in 1 cat with lesions that infringed only on the medial-ventral aspect of the LC-subcoeruleus. These findings suggest that hemodynamic information responsible for the reflex response of ACTH to hemorrhage of this magnitude passes through a discrete region of the dorsal rostral pons.

Adrenocorticotropic Hormone↗

Inhibitory and facilitatory areas of the rostral pons mediating ACTH release in the cat.

To define the role of the rostral pons in the control of release of ACTH, we stimulated electrically (30 sec, 200 muA, 50 Hz) 128 sites in the dorsal rostral pons of 20 cats anesthetized with chloralose/urethane. Responses of arterial pressure to electrical stimulation were prevented by lesions placed previously in the medulla. Plasma concentrations of ACTH were measured by radioimmunoassay. Active areas consisted of three regions: 1) lateral inhibitory: Locus subcoeruleus and anteroventral locus coeruleus (mean deltaACTH: -189, -164, -145 pg/ml at 1.5,3.0 and 6.0 min respectively, P less than 0.01);2) intermediate facilitatory:principal locus coeruleus and lateral ventral tegmental nucleus (mean deltaACTH: +81, +68, +37 pg/ml; P less than 0.05); and 3) medial inhibitory: dorsal tegmental nucleus, dorsal raphé and medial ventral tegmental nucleus (mean deltaACTH; -211, -212, -115 pg/ml; P less than 0.01). The former two areas received direct projections from medullary neurons activated or inhibited by atrial stretch, and, in turn, give rise to adrenergic and cholinergic projections to the medial hypothalamus. Since the release of ACTH is inversely correlated with right atrial stretch, the results suggest that the lateral inhibitory area and the intermediate facilitatory area are involved in mediation of changes in release of ACTH in response to hemodynamic changes.

Adrenocorticotropic Hormone↗

Damage to the reticulotegmental nucleus of the pons in spinocerebellar ataxia type 1, 2, and 3.

BACKGROUND: The reticulotegmental nucleus of the pons (RTTG) is among the precerebellar nuclei of the human brainstem. Although it represents an important component of the oculomotor circuits crucial for the accuracy of horizontal saccades and the generation of horizontal smooth pursuits, the RTTG has never been considered in CAG repeat or polyglutamine diseases. METHODS: Thick serial sections through the RTTG of 10 patients with spinocerebellar ataxias (SCAs) assigned to the CAG repeat or polyglutamine diseases (2 SCA-1 patients, 4 SCA-2 patients, and 4 SCA-3 patients) were stained for neuronal lipofuscin pigment and Nissl material. RESULTS: The unconventionally thick tissue sections revealed the hitherto overlooked involvement of the RTTG in the degenerative processes underlying SCA-1, SCA-2, and SCA-3, whereby in one of the SCA-1 patients, in two of the SCA-2 patients, and in all of the SCA-3 patients, the RTTG underwent a conspicuous loss of its nerve cells. CONCLUSIONS: Neurodegeneration may not only affect the cranial nerve nuclei (i.e., oculomotor and abducens nuclei) of SCA-1, SCA-2 and SCA-3 patients integrated into the circuits, subserving accuracy of horizontal saccades and the generation of horizontal smooth pursuits, but likewise involves the premotor networks of these circuits. This may explain why the SCA-1, SCA-2, and SCA-3 patients in this study with a heavily damaged reticulotegmental nucleus of the pons developed dysmetric horizontal saccades and impaired smooth pursuits during the course of the disease.

Adolescent↗