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PubMed1998

Single-voxel proton magnetic resonance spectroscopy of the pons and cerebellum in patients with schizophrenia: a preliminary study.

Magnetic resonance spectroscopy (MRS) is a non-invasive functional imaging technique that can measure various brain tissue metabolites such as N-acetylaspartate (NAA), choline (Cho), creatine-phosphocreatine (Cr), myo-inositol (mI) and other metabolites. Morphological studies have indicated the pons and cerebellum as possible sites of abnormal functioning in schizophrenic patients. This study examines schizophrenic patients for the presence of abnormalities in proton MRS (1H-MRS) measured metabolites in two regions of the posterior fossa. Twelve schizophrenic patients and eight non-schizophrenic control subjects were studied by measuring the ratios of NAA/Cr, Cho/Cr and mI/Cr from 1H-spectra obtained from the pons and right or left cerebellum using an integrated MRI/MRS protocol. Spectra were obtained from a voxel in the pons and voxels from the left and/or right lateral cerebellum. Data were analyzed in the absorption mode and fitted to Lorentzian lineshapes using a Marquart algorithm. Significantly lower NAA/Cr ratios were found in the pons of schizophrenic patients than in the control subjects, but not in the cerebellum. This study is the first to measure brain tissue metabolites using 1H-MRS in the pons and cerebellum of schizophrenic patients. Significant alterations of 1H-MRS metabolites may suggest the involvement of the posterior fossa as a part of the pathological substrate underlying schizophrenia.

Adult↗
PubMed2005

Antioxidant responses to chronic hypoxia in the rat cerebellum and pons.

Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH) and sleep fragmentation and deprivation. Exposure to CIH results in oxidative stress in the cortex, hippocampus and basal forebrain of rats and mice. We show that sustained and intermittent hypoxia induces antioxidant responses, an indicator of oxidative stress, in the rat cerebellum and pons. Increased glutathione reductase (GR) activity and thiobarbituric acid reactive substance (TBARS) levels were observed in the pons and cerebellum of rats exposed to CIH or chronic sustained hypoxia (CSH) compared with room air (RA) controls. Exposure to CIH or CSH increased GR activity in the pons, while exposure to CSH increased the level of TBARS in the cerebellum. The level of TBARS was increased to a greater extent after exposure to CSH than to CIH in the cerebellum and pons. Increased superoxide dismutase activity (SOD) and decreased total glutathione (GSHt) levels were observed after exposure to CIH compared with CSH only in the pons. We have previously shown that prolonged sleep deprivation decreased SOD activity in the rat hippocampus and brainstem, without affecting the cerebellum, cortex or hypothalamus. We therefore conclude that sleep deprivation and hypoxia differentially affect antioxidant responses in different brain regions.

Animals↗
PubMed1987

Lesions in the upper lateral pons abolish the hypoxic depression of breathing in unanaesthetized fetal lambs in utero.

1. The effects of stereotaxically placed lesions made throughout the mid-brain and upper pons were studied in chronically instrumented fetal lambs from 120 days gestation, after recovery in utero. 2. Isocapnic hypoxia caused an increase in the rate and depth of breathing movements in fetuses in which bilateral lesions encompassed the upper lateral pons in the region of and slightly rostral to the principal sensory and motor nuclei of the trigeminal nerve. 3. Fetal lambs with lesions which did not bilaterally encompass the upper lateral pons showed the normal fetal depressive response to hypoxia. 4. None of the lesions induced permanent continuous breathing as previously described in mid-brain transected fetuses, although periods of continuous breathing lasting several hours were seen at times in some fetuses with lesions in the upper lateral pons. 5. It is concluded that an area in the lateral pons close to areas with well known involvement in respiratory control is involved in the hypoxic depression of breathing in the fetal lamb.

Animals↗
PubMed1992

Activity of monkey frontal eye field neurons projecting to oculomotor regions of the pons.

1. This study identified neurons in the rhesus monkey's frontal eye field that projected to oculomotor regions of the pons and characterized the signals sent by these neurons from frontal eye field to pons. 2. In two behaving rhesus monkeys, frontal eye field neurons projecting to the pons were identified via antidromic excitation by a stimulating microelectrode whose tip was centered in or near the omnipause region of the pontine raphe. This stimulation site corresponded to the nucleus raphe interpositus (RIP). In addition, electrical stimulation of the frontal eye field was used to demonstrate the effects of frontal eye field input on neurons in the omnipause region and surrounding paramedian pontine reticular formation (PPRF). 3. Twenty-five corticopontine neurons were identified and characterized. Most frontal eye field neurons projecting to the pons were either movement neurons, firing in association with saccadic eye movements (48%), or foveal neurons responsive to visual stimulation of the fovea combined with activity related to fixation (28%). Corticopontine movement neurons fired before, during, and after saccades made within a restricted movement field. 4. The activity of identified corticopontine neurons was very similar to the activity of neurons antidromically excited from the superior colliculus where 59% had movement related activity, and 22% had foveal and fixation related activity. 5. High-intensity, short-duration electrical stimulation of the frontal eye field caused omnipause neurons to stop firing. The cessation in firing appeared to be immediate, within < or = 5 ms. The time that the omnipause neuron remained quiet depended on the intensity of the cortical stimulus and lasted up to 30 ms after a train of three stimulus pulses lasting a total of 6 ms at an intensity of 1,000 microA. Low-intensity, longer duration electrical stimuli (24 pulses, 75 microA, 70 ms) traditionally used to evoke saccades from the frontal eye field were also followed by a cessation in omnipause neuron firing, but only after a delay of approximately 30 ms. For these stimuli, the omnipause neuron resumed firing when the stimulus was turned off. 6. The same stimuli that caused omnipause neurons to stop firing excited burst neurons in the PPRF. The latency to excitation ranged from 4.2 to 9.8 ms, suggesting that there is at least one additional neuron between frontal eye field neurons and burst neurons in the PPRF. 7. The present study confirms and extends the results of previous work, with the use of retrograde and anterograde tracers, demonstrating direct projections from the frontal eye field to the pons.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1976

[Strychnine-neuronographic study of orbital cortex projections to structures of the pons varolii].

In adult cats, it was shown that the orbital cortex had direct contra - and ipsilateral projections to oral and caudal reticular nuclei of the pons, to caudal part of the Guden neuclei, to pons covering nucleus, to sulure nucleus, to trigeminal nuclei, and to such conducting formations, as the trapezoid body and pyramidal tract. The orbital gyri connections were mostly ipsilateral and to the caudal part of caudal reticular nucleus of the pons, to oral part of the reticular giganto-cellular nucleus, and to the own pons nuclei. The highest firing rate and amplitude were recorded in the inhibition zone of the reticular formation (the site of overlapping of the oral and caudal reticular nuclei of the pons).

Animals↗
PubMed2005

Paraoxonases (PONs) 1, 2, and 3 are expressed in human and mouse gastrointestinal tract and in Caco-2 cell line: selective secretion of PON1 and PON2.

The paraoxonase (PON) family contains three genes (PON1/2/3) that are believed to be involved in the protection against oxidative stress. PON1 and PON3 are circulating in serum attached to high-density lipoprotein fraction (HDL), whereas PON2 is ubiquitously expressed. The intestine is the second major organ that synthesizes lipoproteins; therefore, we examined PON mRNA expression and protein levels in gastrointestinal biopsies from humans, from C57BL6 mice, and from Caco-2 cells, a colon carcinoma-derived cell line that exhibits properties of intestinal epithelium at differentiation. PON 1/2/3 mRNA and proteins were present in human biopsies with variable expression among different gastrointestinal segments. Only PON2 and PON3 were present in mice. All PON mRNA, proteins, and enzymatic activities were present in Caco-2 cells. Oxidation of CaCo-2 cells with ferrum ascorbate had no significant effect on PON mRNA expression, but it increased paraoxonase and lactonase activity, whereas statinase activity was decreased. We showed polarized secretion of PON1 (basolateral) and PON2 (apical) into Caco-2 culture medium, raising the possibility that intestine is capable of producing and releasing PON1 and PON3 to the circulation, whereas PON2 is released at the brush-border membrane to intestinal lumen where it may perform another yet unclear function.

Animals↗
PubMedDate not supplied

Metastatic hepatoma originating from the pons hepatis presenting extrahepatic growth--classification of different patterns covering REX's recessus.

A metastatic liver carcinoma which developed from the pons hepatis and presented as an extrahepatic mass on ultrasonography and computed tomography is reported. There have been no other reports of hepatoma documenting the extrahepatic growth developed from the pons hepatis. Herein we study the frequency of the pons hepatis and classify the form of REX's recessus. Of 125 cases that underwent upper abdominal operation, 46 cases (38%) had nothing under REX's recessus (Type I), 48 cases (37%) had a fibrous tissue under REX's recessus (Type II), and 31 cases (25%) had a pons hepatis (Type III). In Type III, some cases suggested that the pons hepatis was ready to disconnect from side to side. We conclude that Type II is a modified form of Type III, and Type I is a modified form of Type II.

Carcinoma, Hepatocellular↗
PubMed1996

Immunocytochemical evaluation of the blood-brain barrier to endogenous albumin in the olfactory bulb and pons of senescence-accelerated mice (SAM).

The blood-brain barrier (BBB) to endogenous albumin was studied in the olfactory bulb and pons of the senescence-accelerated prone (SAMP8) mouse and senescence-accelerated resistant (SAMR1) mouse strains by using a quantitative immunocytochemical procedure. Ultrathin sections of Lowicryl K4M-embedded samples were exposed to anti-mouse albumin antiserum followed by protein A-gold. Morphometric analysis of the electron micrographs revealed that in the olfactory bulb of both groups of animals, especially in the internal granular layer, some percentage of capillaries and slightly larger microvessels showed leakage of albumin. However, this percentage was larger in SAMP8 than in SAMR1 mice. In the pons, no significant differences in the permeability of blood microvessels were observed in both groups of mice, although a small fraction of capillaries in SAMP8 mice showed limited extravasation of blood plasma albumin. These observations indicate that the BBB in the olfactory bulb of control and SAMP8 mice is not as tight as it is in the pons or in the previously examined cerebral cortex. The labelling density of the neuropil was slightly higher than in the cerebral cortex, suggesting that albumin may have extravasated locally, in addition to having acces to the parenchyma of the olfactory bulb and pons from neighbouring areas supplied with the non-BBB-type of microvasculature. Furthermore, the data obtained suggest that there is limited (segmental), premature age-related impairment of the BBB function in SAMP8 mice.

Aging↗
PubMed1982

Independent origin and modulation of vasopressin as compared to dynorphin and alpha-neo-endorphin in the medulla-pons of the rat.

Bilateral, radiofrequency destruction of the hypothalamic paraventricular nucleus resulted in a pronounced depression in levels of immunoreactive (ir-) vasopressin (VP) in the medulla-pons of rats. The contents of ir-dynorphin1-17 (DYN), ir-DYN1-8 and ir-alpha-neo-endorphin (alpha-NE) therein were not, in contrast, affected. Exposure of naive rats to acute foot-shock stress was associated with an elevation in levels of ir-VP in the medulla-pons whereas those of ir-DYN, ir-DYN1-8 and ir-alpha-NE were not significantly altered. The data indicate that the paraventricular nucleus is a major source of ir-VP but not of ir-DYN, ir-DYN1-8 or ir-alpha-NE in the medulla-pons, and that these pools of ir-VP, in contrast to those of ir-DYN, ir-DYN1-8 and ir-alpha-NE, are involved in the response to stress. It is concluded that ir-DYN, ir-DYN1-8 and ir-alpha-NE exist in (a) neuronal network(s) independent of that of ir-VP in the medulla-pons of the rat.

Animals↗
PubMedDate not supplied

Development of ferritin-containing cells in the pons and cerebellum of the human brain.

The distribution and development of ferritin-containing cells were studied in the pons and cerebellum of human fetuses up to adults, using an immunohistochemical method. The predominant cell type labeled with antiserum to ferritin in the pons and cerebellum was morphologically oligodendrocytes. In the pons, positive cells appeared at 21 weeks of gestation in the reticular formation, and longitudinal and transverse fibers, and at 25 weeks of gestation in pontine nuclei. They increased with age from 33 weeks to infancy. In the cerebellum, positive cells appeared at 25 weeks of gestation in the cerebellar white matter and granular layer. They increased from 29 to 40 weeks of gestation in the white matter, and to childhood in the granular layer. The time of appearance of positive cells in the pons and cerebellum is earlier than in the cerebrum, like myelination. This development of ferritin-positive glia may be related to maturation of oligodendrocytes as well as being the basis of myelination.

Adolescent↗
PubMed2004

Facilitation of respiratory rhythm by a mu-opioid agonist in newborn rat pons-medulla-spinal cord preparations.

We investigated the effect of a mu-opioid agonist, DAGO, on the respiratory frequency of pons-medulla-spinal cord preparations from newborn rats. Bath application of a low concentration of DAGO (0.2 microM) facilitated respiratory rhythm in pons-medulla-spinal cord preparations, whereas it induced respiratory depression in medulla-spinal cord preparations (without pons). At a higher concentration (1.0 microM), at which the inspiratory burst generation in the medulla was strongly depressed, the respiratory rhythm in half of the pons-medulla-spinal cord preparations increased and then decreased, thus showing a biphasic response. In the other half of these preparations, only the facilitatory effect was observed. The burst rate of pre-inspiratory neurons in the rostral ventrolateral medulla was also facilitated by DAGO application. Such facilitation of the respiratory rhythm is probably due to disinhibition of a pontine inhibitory system. Our findings also suggest the existence of a pontine excitatory system, which is depressed by the pontine inhibitory system under control conditions.

Action Potentials↗
PubMed2000

Ventrolateral pons mediates short-term depression of respiratory frequency after brief hypoxia.

The respiratory response to hypoxia is dynamic in the adult anesthetized Sprague-Dawley rat. Hypoxia elicits acute increases in both tidal volume (VT) and respiratory frequency (fR) followed by short-term increases in VT and short-term decreases in fR. After brief hypoxia (<1 min), recovery of the breathing pattern is again dynamic, where both VT and fR decrease immediately, but where VT remains above, and fR drops below, baseline. These acute changes are followed by a short-term progressive decrease in VT and increase in fR to baseline. We have identified a potential neural mechanism that depends on the integrity of the ventrolateral (vl) pons. Our studies show that: (a) blockade of activity in the vl pons prevents the short-term decrease in fR after hypoxia (b) stimulation of the vl pons decreases fR, and (c) vl pontine expiratory neurons are activated after hypoxia. These neurons may not be acting through alpha(2) -adrenergic receptors, but their effect does depend on NMDA-type receptor function. We conclude that the vl pons is a critical element in the pontomedullary network that generates and modulates the fR response to acute hypoxia.

Animals↗
PubMed2000

Atonia-related regions in the rodent pons and medulla.

Electrical stimulation of circumscribed areas of the pontine and medullary reticular formation inhibits muscle tone in cats. In this report, we present an analysis of the anatomical distribution of atonia-inducing stimulation sites in the brain stem of the rat. Muscle atonia could be elicited by electrical stimulation of the nuclei reticularis pontis oralis and caudalis in the pons as well as the nuclei gigantocellularis, gigantocellularis alpha, gigantocellularis ventralis, and paragigantocellularis dorsalis in the medulla of decerebrate rats. This inhibitory effect on muscle tone was a function of the intensity and frequency of the electrical stimulation. Average latencies of muscle-tone suppressions elicited by electrical stimulation of the pontine reticular formation were 11.02 +/- 2.54 and 20.49 +/- 3.39 (SD) ms in the neck and in the hindlimb muscles, respectively. Following medullary stimulation, these latencies were 11.29 +/- 2.44 ms in the neck and 18.87 +/- 2. 64 ms in the hindlimb muscles. Microinjection of N-methyl-D-aspartate (NMDA, 7 mM/0.1 microliter) agonists into the pontine and medullary inhibitory sites produced muscle-tone facilitation, whereas quisqualate (10 mM/0.1 microliter) injection induced an inhibition of muscle tone. NMDA-induced muscle tone change had a latency of 31.8 +/- 35.3 s from the pons and 10.5 +/- 0. 7 s from the medulla and a duration of 146.7 +/- 95.2 s from the pons and 55.5 +/- 40.4 s from the medulla. The latency of quisqualate (QU)-induced reduction of neck muscle tone was 30.1 +/- 37.9 s after pontine and 39.5 +/- 21.8 s after medullary injection. The duration of muscle-tone suppression induced by QU injection into the pons and medulla was 111.5 +/- 119.2 and 169.2 +/- 145.3 s. Smaller rats (8 wk old) had a higher percentage of sites producing muscle-tone inhibition than larger rats (16 wk old), indicating an age-related change in the function of brain stem inhibitory systems. The anatomical distribution of atonia-related sites in the rat has both similarities and differences with the distribution found in the cat, which can be explained by the distinct anatomical organization of the brain stem in these two species.

Animals↗
PubMed2003

Effects of alcohol dependence comorbidity and antipsychotic medication on volumes of the thalamus and pons in schizophrenia.

OBJECTIVE: Postmortem and in vivo brain imaging studies have identified abnormalities in the thalamus and the pons in both schizophrenia and alcoholism. The authors sought to determine whether patients with both schizophrenia and alcohol dependence would manifest exaggerated volume deficits in either structure. METHOD: Volumetric measures of the left and right thalamus and the pons were derived from magnetic resonance imaging scans obtained from 27 patients with schizophrenia, 19 patients with schizophrenia and comorbid alcohol dependence, 25 patients with alcohol dependence without comorbid axis I disorders, and 51 healthy comparison subjects. RESULTS: The alcohol-dependent patients had significant volume deficits in both the thalamus and the pons. Among patients with schizophrenia, there were no differences in thalamus volumes between those with and without comorbid alcohol dependence. However, patients with schizophrenia who were taking atypical antipsychotic medications had bilateral thalamic deficits, whereas those taking typical neuroleptics did not. Patients with schizophrenia and comorbid alcohol dependence had deficits in the pons. CONCLUSIONS: Patients with schizophrenia and comorbid alcohol dependence are at risk for alcohol-related reduction of pontine structures that are not necessarily affected by schizophrenia per se. The effect of alcohol dependence on the thalamus in schizophrenic patients may be mitigated by the type of neuroleptic medication they receive.

Adult↗
PubMed1999

[Medulloblastoma originating in the pons].

Medulloblastoma usually originates in the cerebellum. We report here a case of medulloblastoma originating in the pons. Pontine medulloblastoma is extremely rare, with only one report in the literature. An 11-year-old girl was admitted to our hospital with vertigo. Magnetic resonance imaging (MRI) revealed a tumor originating in the pons. On the 4th day after admission, the tumor bled. Because the patient's life was in danger from brain herniation, hematoma removal and tumor resection were carried out. The diagnosis was medulloblastoma. After surgery, the patient received radiation therapy and chemotherapy. Unlike tumors originating in the cerebellum, this tumor did not seem to be effectively reduced by these therapies. Radiation therapy and chemotherapy may not be effective for medulloblastoma originating in the pons. We considered it necessary to make a histological diagnosis even though the tumor originated in the pons and resection was difficult technically.

Brain Neoplasms↗
PubMed2003

A surgical technique for safely placing a drug delivery catheter into the pons of primates: preliminary results of carboplatin infusion.

OBJECTIVE: We sought to develop a neurosurgical procedure to access the pons with a drug delivery device for chronic therapy and collect preliminary data on the toxicity of direct infusions of carboplatin in primates. METHODS: We made midline incisions on five cynomolgus monkeys, identified the inion, made a burr hole 2.5 cm below the inion, and inserted a catheter through the cerebellum into the roof of the pons. Pumps that infused saline for 90 days or carboplatin solutions for 30 to 35 days at 10 microl/d were placed subcutaneously in the low cervical/high thoracic region. Monkeys were assessed by computed tomography and magnetic resonance imaging, laboratory studies, daily neurological observation, postmortem examinations, and histopathology. RESULTS: Monkeys infused with saline and 82 microg of carboplatin remained neurologically intact throughout the infusion periods. Serial imaging showed that the catheter tip was in the pons and revealed no evidence of hemorrhage, edema, or migration. Two monkeys infused with up to 850 microg of carboplatin showed hyperintense magnetic resonance imaging signals at Days 15 and 18 and neurological deficits at approximately Week 3. Platinum levels greater than 10 ng/mg tissue were detected over a distance of 1 cm in tissue slices. Histopathology demonstrated significant tissue necrosis around the tip of the catheter. CONCLUSION: The pons of monkeys is safely accessed with a catheter for drug delivery by using a posterior midline approach. Clinical observations, radiographic imaging, and laboratory tests of animals infused with saline for 3 months or 0.26 mg/ml of carboplatin for 1 month were unremarkable. Neurotoxicity was seen with dose levels of 2.6 mg/ml of drug for 1 month. This procedure offers opportunities for examining the toxicity of brainstem antitumor therapy in primates.

Animals↗
PubMed2003

[Direct trans-sylvian approach to the ventrolateral pons in surgical management of large cystic cavernous malformations of the brain stem in children].

OBJECTIVES: In the study surgical indications are reviewed and the effect of the applied surgical technique on long-term treatment outcome in children with large cystic brainstem cavernous malformations is evaluated. METHOD: Clinical data of 5 patients treated surgically for large cystic cavernous malformations of the pons in the years 1995-2001 were retrospectively evaluated. In all the cases the transsylvian approach to the ventrolateral pons with splitting of the crus cerebri was used to reach cavernoma within the cystic cavity. The long-term follow up (mean 4.9 years) included a complete neurological examination and annual MRI studies. RESULTS: At least one hemorrhagic episode was diagnosed in all the cases, while bleeding to the pons, with clinical course mimicking that of stroke, was noted twice in 3 patients. All the episodes confirmed by MRI imaging appeared to be intralesional. The malformations ranged in size from 30 to 50 mm (mean 36.9 mm). Their most characteristic MRI features were not only the localization in the pontine structure exclusively i.e. within the natural anatomical barriers separating the pons from the midbrain and medulla, but also the growth pattern corresponding to that of brainstem benign gliomas. The patients' mean preoperative KPS score was 60 (30 to 90). Cavernous hemangiomas were totally removed in 3 out of 5 cases. One patient with partially removed lesion presented after a year recurrent hemorrhage and new neurological deficits that required a second stage surgery. In all but one case transient complications included some new cranial nerve, motor and sensory deficits that influenced the patients' immediate postoperative KPS assessment, with the mean score of 48. In a follow-up assessment at 1.5 to 7 years, a significant amelioration of both their neurological status and quality of life was found, with KPS scores from 70 to 90 (mean score 80). Annual MRI examinations showed extensive hemosiderin deposits within the pontine tissue in 3 cases of totally removed cavernous hemangiomas and this image was stable during the follow-up period. CONCLUSIONS: The findings suggest that resection of large pontine cavernomas in children is indicated in cases of symptomatic hemorrhage with lesions approaching the pial surface, or surrounded by a small margin of normal tissue. Recurrent hemorrhages are intralesional (i.e. limited to pontine structures by the natural anatomical barriers), resulting in a "cyst-like" growth of malformations mimicking that of focal neoplasms and in compression of the brain stem tissue rather than in a direct hemorrhagic insult.

Adolescent↗
PubMed1988

Differentiation of muscarinic cholinergic receptor subtypes in human cortex and pons: implications for anti-motion sickness therapy.

Radioligand binding studies were used to analyze muscarinic cholinergic receptor subtypes in human cortex and pons. Muscarinic cholinergic receptors were labeled by 3H-quinuclidinyl benzilate (3H-QNB). Scopolamine was equipotent in both brain regions and did not discriminate subtypes of 3H-QNB binding. By contrast, the M1 selective antagonist pirenzepine was approximately 33-fold more potent in human cortex than pons. Carbachol, a putative M2 selective agonist, was more than 100-fold more potent in human pons than cortex. These results demonstrate that the human pons contains a relatively large proportion of carbachol sensitive muscarinic cholinergic receptors. Drugs targeted to this subpopulation of muscarinic cholinergic receptors may prove to be effective anti-motion sickness agents with less side effects than scopolamine.

Carbachol↗