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PubMed1997

Cell death in perinatal hypoxic-ischaemic brain injury.

Perinatal hypoxic brain injury is a major cause of death and morbidity, in which the onset of injury can be prenatal, and the effects may be delayed. Selective neuronal necrosis, with isolated karyorrhectic nuclei in the pons, is a common pattern of injury in mature perinatal deaths. Other evidence implicates apoptosis in hypoxic brain injury. In this study the mode of cell death in hypoxic injury was investigated in 11 fresh stillbirths and 10 neonatal deaths. Sections of pons were stained using several methods including terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labelling (TUNEL) and immunocytochemistry. Karyorrhectic nuclei were counted on adjacent haemotoxylin and eosin sections. A high percentage of apoptotic cells was significantly associated with the presence of karyorrhexis in the pons, but there were five stillbirths in whom apoptosis in the pons was the sole evidence of hypoxic brain injury. PCNA positive neuronal nuclei were seen in 19 out of 21 cases. The results suggest that both apoptosis and necrosis are occurring following hypoxic injury, so that the pattern of injury in the pons may be better termed 'selective neuronal death'. Variations in severity and duration of the insult might explain the differences between cases. The presence of PCNA-positive neurons may suggest DNA repair in these nuclei, which might be activated at an early stage of apoptosis. However the precise mechanism by which apoptosis is induced in hypoxic brain injury remains to be elucidated.

Apoptosis↗
PubMed1977

Auditory evoked brain stem potentials in a case of "locked-in" syndrome.

Auditory evoked brain stem potentials were measured in a patient with occlusion of the basilar artery about 7 mm above its origin, resulting in the "locked-in" syndrome due to infarction at the junction of the lower one third and upper two thirds of the pons. The first three waves of the evoked response originating from the acoustic nerve and auditory nuclei in the caudal pons were normal in wave form, peak latency, and voltage level. Waves IV and V, generated in the region of the lateral lemniscus and inferior colliculus in rostral pons and caudal midbrain, demonstrated prolonged peak latency and reduced voltage, indicative of slowed neural conduction in the pons above the level of the superior olivary complex. These findings suggest that auditory evoked potential recordings may have considerable value in the localization of brain stem disorders.

Acoustic Stimulation↗
PubMed1998

Collateral branch formation related to cellular structures in the axon tract during corticopontine target recognition.

The corticopontine projection develops exclusively by collateral branches that form along the length of corticospinal axons days after they have passed their hindbrain target, the basilar pons. In vitro evidence suggests that the basilar pons releases a diffusible activity that initiates and directs the growth of collateral branches. This study investigates whether contact-dependent mechanisms may also influence the formation of collateral branches. By using immunocytochemistry, electron microscopy, and neuronal tracing techniques, we examined the region of the axon tract, the cerebral peduncle, overlying the basilar pons for cellular structures that correlate spatially and temporally with collateral branch formation. We found that radial glia are excluded from the tract. Oligodendrocyte precursors are found only at low density. Although mature astrocytes are absent, immature astrocytes are present throughout the tract. However, our evidence does not suggest a direct role for glial cell types in collateral branch formation. In contrast, dendrites of basilar pontine neurons are transiently present in the tract during the time of collateral branch formation. Although collateral branches are observed in regions of the tract devoid of dendrites, the orientation and location of most collateral branches correlates at the light microscopic level with dendrites. Electron microscopy reveals sites of increased collateral branch formation near neuronal cell bodies or dendrites. However, cell processes, whether dendritic or otherwise, are rarely found in direct contact with collateral branch points. A common and unexpected feature is the bundles of corticopontine collateral branches, oriented transversely to their parent corticospinal axons and directed across the tract to the basilar pons. Dendrites were often apposed to or embedded within the transverse bundles. These findings suggest that dendrites are not essential for collateral branch formation but that they may enhance this process and define discrete preferred locations for collateral branch initiation and elongation within the cerebral peduncle.

Animals↗
PubMed2005

Somatotopic organization of the corticospinal tract in the human brainstem: a MRI-based mapping analysis.

To investigate the incompletely understood somatotopical organization of the corticospinal tract in the human brainstem, we performed a voxel-based statistical analysis of standardized magnetic resonance scans of 41 prospectively recruited patients with pyramidal tract dysfunction caused by acute brainstem infarction. Motor hemiparesis was rated clinically and by the investigation of motor evoked potentials to arms and legs. Infarction affected the pons in 85% of cases. We found the greatest level of significance of affected brainstem areas between the pontomesencephalic junction and the mid pons. Lesion location was significantly more dorsal in patients with hemiparesis affecting more proximal muscles and was significantly more ventral in patients with predominantly distal limb paresis. Comparison of magnetic resonance lesion from patients with paresis predominantly affecting arm or leg did not show significant topographical differences. We conclude that a topographical arm/leg distribution of corticospinal fibers is abruptly broken down as the descending corticospinal tract traverses the pons. Corticospinal fibers, however, follow a somatotopical order in the pons with fibers controlling proximal muscles being located close to the reticular formation in the dorsal pontine base, and thus more dorsal than the fibers controlling further distal muscle groups.

Adult↗
PubMed1975

The central adrenergic system. An immunofluorescence study of the location of cell bodies and their efferent connections in the rat utilizing dopamine-beta-hydroxylase as a marker.

A sensitive immunofluorescence technique was used to describe systematically the distrubution of dopamine-beta-hydroxylase (DBH)-containing cell bodies, non-terminal fiber pathways, and terminal fields in the brain of the male albino rat. DBH is the enzyme that catalyzes the conversion of dopamine to noradrenaline, and as such is useful as an anatomical marker for noradrenaline and possibly adrenaline neurons. The enzyme is not present in dopamine- or indolamine-containing neurons. Ten micron frozen sections (1-in 20 series) were prepared in the frontal, sagittal, and horizontal planes from the olfactory bulb to the upper cervical segments of the spinal cord; adjacent sections in each plane were stained for DBH and for cells (toluidine blue=azure II). An atlas consisting of 40 projection drawings of selected frontal sections illustrates the results of the investigation. DBH perikarya are confined to three groups in the pons and medulla: the well defined locus coeruleus, a more diffuse but continuous subcoeruleus group that arches through the pons and ventral medulla, and a third dorsal medullary group centered in the dorsal motor nucleus of the vagus. A single principal adrenergic fiber system distributes a great many of the axons from these neuron groups to a majority of nuclear areas in the brain. In the pons and medulla two components of the fiber system may be distinguished. A medullary branch may be followed from the posterior aspect of the subcoeruleus group dorsally and then anteriorly through the lateral tegmental field and ventral aspect of the vestibular complex to a position subjacent to the locus coeruleus, where it is joined by a subcoeruleus branch consisting of a large number of fibers coursing among cells along the length of the subcoeruleus group, and by fibers arising from the locus coeruleus. Anterior to the locus coeruleus the principal adrenergic bundle courses as a single fiber tract immediately ventrolateral to the central gray in the mesencephalon and in the zona incerta and substantia innominata in the diencephalon. At the level of the septal area separate bundles reach the cortex dorsally over the genu of the corpus calosum via the medial septal-diagonal band nuclei and the lateral septum and ventrally between the olfactory tubercle and caudate-putamen. In the medulla and pons adrenergic fibers undoubtedly course in both directions. Anterior to the most rostral pontine cell bodies, however, all fibers presumably ascend. Along the course of the bundle distinct branches emerge to innervate circumscribed terminal fields. In addition, certain regions of the brain such as the reticular formation and pontine gray receive diffuse DBH innervation derived from less clearly defined pathways. A small number of areas in the brain contain little or no detectable DBH. These include the caudate-putamen, nucleus accumbens, globus pallidus, olfactory tubercle, subthalamic nucleus, substantia nigra, pretectal area, third, fourth and sixth cranial verve nuclei, and the trapezoid body nucleus.

Animals↗
PubMed2002

Proton magnetic resonance spectroscopy with metabolite nulling reveals regional differences of macromolecules in normal human brain.

PURPOSE: To quantify the macromolecular content in different anatomic brain regions and to evaluate an age dependency of the macromolecular concentrations. MATERIAL AND METHODS: A short echo time Stimulated Echo Acquisition Mode (STEAM) sequence was used without and with inversion recovery metabolite nulling in 8-12 healthy volunteers. Quantitation was achieved by an extended LCModel, and macromolecular resonances at 0.9, 1.4, 2.1, and 3.0 ppm were evaluated. RESULTS: In the cerebellum, the 1.4, 2.1, and 3.0 ppm resonances were highest compared to all other regions (P < 0.02); the 0.9 ppm resonance was significantly higher than that of pons (P < 0.01). In the motor cortex, the 0.9, 1.4, and 2.1 ppm resonances were higher than those of white matter and pons (P < 0.02). Pons and white matter did not differ significantly from each other. A significant correlation of the macromolecular concentrations with the age could not be found. CONCLUSION: There were higher macromolecular concentrations in the cerebellum and motor cortex than in pons or white matter. These were probably due to the higher portions of gray matter in these volumes of interest (VOIs) than in the other regions.

Adult↗
PubMed1978

The pontocerebellar projection of the uvula in the cat.

The occurrence of retrogradely labeled cells in the pontine nuclei was mapped following injections of 0.3-0.4 microliter of a horseradish peroxidase suspension (50% weight/volume) into the uvula (lob. IX of Larsell) in the cat. The uvula was found to receive afferents from three pontine cell collections. One of these is situated in the paramedian pontine nucleus close to the midline. It forms a fairly distinctly outlined longitudinal column of cells and is present at all levels of the pons except most rostrally and caudally. Another group, in the dorsolateral and lateral pontine nuclei, extends as a somewhat shorter cell column in the longitudinal direction. The third region consists of cells within the rostral part of the peduncular nucleus in its dorsomedial region. The pontine projection to the uvula is bilateral, with some preponderance of crossed connections. The projection to the uvula is organized according to the pattern determined previously for pontine projections to other parts of the cerebellum. A single lobule or part of its receives afferents from more than one cell group in the pons. The projecting cells are most often arranged in longitudinal columns. Correlations with data on the termination of afferents to the pons permit some conclusions regarding the sources of information reaching the uvula via the pons. Main sources seem to be the superior and inferior colliculi, the intracerebellar nuclei and the sensorimotor cortices.

Afferent Pathways↗
PubMed1992

Age-related changes in acetylcholinesterase and its molecular forms in various brain areas of rats.

A previous study conducted in this laboratory revealed a decrease in total cholinesterase (total ChE) in the cerebral cortex, hippocampus and striatum in aged rats (24 months) of various strains, as compared with young animals (3 months). The purpose of the present experiments was to extend the study to other brain areas (hypothalamus, medulla-pons and cerebellum) and to assess whether this decrease was dependent on the reduction of either specific acetylcholinesterase (AChE) or butyrylcholinesterase (BuChE) or both. By using ultracentrifugation on a sucrose gradient, the molecular forms of AChE were evaluated in all the brain areas of young and aged Sprague-Dawley rats. In young rats the regional distribution of total ChE and AChE varied considerably with respect to BuChE. The age-related loss of total ChE was seen in all areas. Although there was a reduction of AChE and, to somewhat lesser extent, of BuChE in the cerebral cortex, hippocampus, striatum, and hypothalamus (but not in the medulla-pons or the cerebellum), the ratio AChE/BuChE was not substantially modified by age. Two molecular forms of AChE, namely G4 (globular tetrameric) and G1 (monomeric), were detected in all the brain areas. Their distribution, expressed as G4/G1 ratio, varied in young rats from about 7.5 for the striatum to about 2.0 for the medulla-pons and cerebellum. The age-related changes consisted in a significant and selective loss of the enzymatic activity of G4 forms in the cerebral cortex, hippocampus, striatum, and hypothalamus, which resulted in a significant decrease of the G4/G1 ratio. No such changes were found in the medulla-pons or the cerebellum.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholinesterase↗
PubMed2006

Signal intensity of the normal pontine tegmentum on T2-weighted MR imaging.

On T2-weighted MR images, the pontine tegmentum frequently shows a signal of high intensity in neurologically healthy individuals. We examined whether the signal intensity of the pontine tegmentum normally differs from that of the pontine base. We evaluated the signal intensity of the pontine tegmentum and pontine base on T2-weighted images from 38 neurologically healthy subjects. The subjects included 29 adults (16 males and 13 females, age range 23-48 years, mean age 39.5 years) and 9 children (4 boys and 5 girls (age range 4-9 years mean age 6.5 years). We compared the contrast-to-noise ratio (CNR) between the tegmentum and the base in the upper pons, midpons and lower pons, and evaluated the signal intensity ratio of the tegmentum to the base. The CNR was significantly higher for the tegmentum than the base at each level of the pons (P<0.0001), and the signal intensity ratio of the tegmentum to the base in the upper pons was significantly higher in children than in adults (P<0.005). On T2-weighted images, a high signal intensity of the pontine tegmentum is frequently seen in neurologically healthy subjects. This finding should not be considered abnormal, particularly in children.

Adult↗
PubMed1999

Pontine axonal injury after brain trauma and nontraumatic hypoxic-ischemic brain damage.

Experimental studies have shown that diffuse axonal injury is usually induced by positive or negative acceleration mechanisms. In order to determine the reliability of axonal injury (AI) as a marker of this type of traumatic insult, we compared cases of trauma-induced focal cortical hemorrhage without dural involvement (n = 67) with cases of trauma-induced subdural bleeding without cortical hemorrhage (n = 26). Both groups exhibited a wide range of post-traumatic survival times. The injuries in the first group were caused mainly by direct impact to the head, those in the second by acceleration/deceleration mechanisms. The investigations were based primarily on immunohistochemical demonstration of antibodies targeted to beta-amyloid precursor protein (beta-APP) in the pons as a marker of AI and the results were assessed semiquantitatively. No significant differences were found between the two groups. In both groups AI was detected in 80-100% of cases with survival times of more than 3 h and two thirds of all positive cases showed pronounced positivity. Additional comparison of cases of brain death due to mechanical trauma (n = 14) with cases of brain death due to non-mechanical trauma (n = 18) also disclosed no significant intergroup differences. Finally, investigations of the pons in cases of non-traumatic death due to cerebral hypoxia/ischemia (n = 51) demonstrated AI with the same frequency as in the other groups, although the expression tended to be less pronounced. Our results confirm that beta-APP expression in the pons is a reliable indicator of AI but does not discriminate between injuries caused by traumatic strain or shearing mechanisms and secondary damage due to cerebral hypoxia/ischemia or edema. In the large majority of cases with prolonged post-traumatic survival, it can therefore be assumed that AI in the pons is the consequence of primary and/or secondary events or a combination of both, as is common in non-missile head injury survived for more than 90-120 min. Therefore, positive differentiation of the type of biomechanical event based on this criterion alone is not possible.

Adolescent↗
PubMed1975

The pontine taste area in the rat.

The pontine taste area relays gustatory information from the rostral pole of the solitary nucleus to both the thalamus and ventral forebrain. An electrophysiological investigation of this area was carried out in 3 stages. First, multiunit responses from the dorsal pons were mapped using sapid, thermal, and tactile stimuli applied to the anterior tongue. The gustatory zone lies within and just dorsal and ventral to the brachium conjunctivum as it enters the pons from the cerebellum. Second, gustatory stimuli were applied independently to the anterior and posterior tongue to determine whether receptors in both fields are represented in the pons. Responses with characteristics similar to those obtained from the glossopharyngeal nerve were located on the dorsal edge of the pontine gustatory zone. More ventrally the responses from the posterior tongue mimicked anterior tongue responses, but were of lesser amplitude than the largest anterior responses occurring at the ventral edge of the gustatory zone. Third, 71 single units were isolated in the dorsal pons, and tested for sensitivity to gustatory stimulation of the anterior and posterior tongue separately. More than half the units responded to gustatory stimuli--some from the anterior tongue alone, some from the posterior alone, but most responded to stimuli applied to either field. In the latter instance 7 of 10 units tested continued to respond after anesthetizing the chorda tympani with Xylocaine instilled into the middle ear, thus demonstrating a true glossopharyngeal input. This proves that gustatory information from two distinct receptive fields may converge on the same central neuron.

Animals↗
PubMed1991

Properties of the descending limb of the spinobulbospinal micturition reflex pathway in the cat.

The micturition reflex is thought to be mediated by a spinobulbospinal reflex pathway passing through the rostral pons. This study examined the properties of the descending limb of the reflex pathway by monitoring the responses of the lower urinary tract to stimulation of the pons in the decerebrate cat. Electrical stimulation (300 microseconds pulses at 50 Hz intratrain frequencies, 300-500 ms trains, 0.5-15 V) in the region of the locus coeruleus (P 0.5-3.1/L 2-4/H to -2.75) was used to activate the descending excitatory pathway to the sacral parasympathetic nucleus. Low intensity stimulation induced small amplitude, short duration (14 +/- 11 cm H2O, 10 +/- 3 s) bladder contractions in a partially full bladder, whereas higher intensity stimulation induced large amplitude, long duration (69 +/- 29 cm H2O, 70 +/- 44 s) contractions which were similar to distension-induced reflex micturition contractions. The evoked bladder contractions coincided with a reduction in external urethral sphincter (EUS) EMG activity. Following bilateral L7-S3 dorsal root transection, electrical stimulation of the pons still elicited the small amplitude bladder contractions, but the larger amplitude, long duration micturition contractions were abolished. During these small evoked bladder contractions, a suppression of EUS activity still occurred following deafferentation, indicating a pontine mediated bladder/EUS synergy. It is concluded that the pons can initiate bladder contractions and coordinated bladder-sphincter activity, but that afferent feedback (via the dorsal roots) is needed to maintain the large amplitude micturition contractions.

Animals↗
PubMed1994

Involvement of pontile NMDA receptors in inspiratory termination in rat.

We evaluated the hypothesis that N-methyl-D-aspartate (NMDA) receptors in the rostral pons mediate the off-switch of inspiration in the adult rat. Experiments were performed on decerebrate, vagotomized, paralyzed and ventilated animals. Activity of phrenic nerve was recorded. Small volumes (10 nl) of NMDA antagonists, MK-801 and AP-5, or non-NMDA antagonists, CNQX and DNQX, were injected into the rostral pons. We found that injections of MK-801 reversibly increased the duration of neural inspiration (TI), and the increase was dose-dependent. Injections of AP-5 also increased TI. Injections of the DNQX and CNQX in these same loci resulted in no significant changes in the duration of neural inspiration, expiration or peak phrenic activity (PNA). However, injections of kainic acid (KA, 4.7 mM) in the loci increased TI and decreased PNA. We conclude that neurons regulating the off-switch mechanism are located in the rostral pons. Further, the binding of NMDA receptors in the rostral pons is involved in this off-switch mechanism.

2-Amino-5-phosphonovalerate↗
PubMed1994

Electrical activation and inhibition of respiration in vitro.

The present studies employed the neonatal rat rib-attached brain stem-spinal cord preparation to examine the effects of electrical stimulation of the medulla and the pons on respiratory-like activity. The investigation focused on determining whether electrical stimulation of the medulla can be used to modulate respiratory-like activity, whether electrical stimulation of the pons can inhibit respiratory-like activity, and how the preparation responds when both the medulla and the pons are stimulated simultaneously. The results suggest that: (1) stimulation of the ventromedial part of the medulla entrains the onset and the frequency of respiratory-like electromyographic (EMG) bursting most effectively and drives the respiratory rate as high as 0.4 Hz; (2) both ventromedial and ventrolateral pontine stimulation inhibited respiratory-like EMG bursting, but only ventrolateral pontine stimulation was followed by post-stimulation inhibition; (3) when the medulla and the pons were stimulated simultaneously, pontine stimulation-induced inhibition outweighed medullary stimulation-induced activation and resulted in a temporary cessation of respiratory-like EMG bursting.

Animals↗
PubMed1983

Localization of substance P- and enkephalin-like immunoreactivity in relation to catecholamine-containing cell bodies in the cat dorsolateral pontine tegmentum: an immunofluorescence study.

The distribution of tyrosine hydroxylase-, substance P- and enkephalin-immunoreactive neurons in the cat dorsolateral pons was studied using the indirect immunofluorescence method of Coons. To allow for the visualization of substance P- and enkephalin-immunoreactive cell bodies, colchicine was injected either in the ventricular space or in the cerebral tissue. The distribution of the tyrosine hydroxylase-immunoreactive cell bodies corresponded with the well-known distribution of catecholamine cells in this area of the brain. The observation of adjacent sections treated separately with tyrosine hydroxylase- and enkephalin-antiserum revealed that most catecholaminergic cells contain enkephalin-immunoreactivity. In addition to this catecholamine-enkephalin cell population, a moderate number of substance P-immunoreactive cell bodies was found in dorsolateral pons. The peribrachial nuclei were found to be densely supplied with substance P- and enkephalin-immunoreactive fibers, whereas the medial subdivisions, which contain the majority of the catecholamine cells in the dorsolateral pons, display a moderate number of immunoreactive fibers. These results are suggestive of interactions between peptide-containing and catecholaminergic neurons and also between-peptide-containing and non-catecholamine-containing neurons in the cat dorsolateral pons.

Animals↗
PubMedDate not supplied

Relationship between levels of cyclic nucleotides and gamma-aminobutyric acid during ethanol withdrawal in rats.

Cyclic nucleotide and gamma-aminobutyric acid (GABA) levels were measured in four brain areas of control rats and rats undergoing ethanol withdrawal. Cyclic adenosine 3',5' monophosphate (cyclic AMP) was increased in the cerebral cortex and pons-medulla oblongata; cyclic guanosine 3',5'-monophosphate (cyclic GMP) was increased in the cerebellum and cerebral cortex; and GABA was decreased in the cerebellum, subcortex and pons-medulla oblongata. Individual values in withdrawn animals were correlated and subjected to a factor analysis. One of the common factors identified by this analysis was important for all but one of the levels which changed during ethanol withdrawal. Significant correlations of levels correlated with this factor included a negative correlation between cyclic GMP and GABA levels in the cerebellum, a positive correlation between cyclic GMP levels in the cerebellum and cyclic AMP levels in the pons-medulla oblongata and a positive correlation between cyclic AMP levels in the pons-medulla oblongata and cerebral cortex. These results indicate that multiple brain areas and neurotransmitters are involved in ethanol withdrawal.

Alcoholism↗
PubMedDate not supplied

Thallium increases monoamine oxidase activity and serotonin turnover rate in rat brain regions.

The effect of thallium acetate administration on monoaminergic pathways was studied in male Wistar rats using 30 mg/kg and 50 mg/kg acute IP doses. We found that thallium activated both monoamine oxidase (MAO) activity and serotonin turnover rate in rat brain regions, that may contribute to the neuronal damage mechanism of the agent. MAO activity in midbrain and pons was increased at both doses (at 30 mg/kg dose by 27.7% and 37%; at 50 mg/kg dose by 48% and 47%, respectively vs. control group). Serotonin turnover rate in pons was also increased at the 30 mg/kg dose (172%) while midbrain and pons serotonin turnover was increased only at the 50 mg/kg dose (56% and 166%, respectively vs. control group). Dopamine turnover rate was not significantly changed. The results indicate that thallium induced a significant increase in pons and midbrain MAO activity and also in serotonin turnover rate as compared with control animals, and this could led to behavioral and toxic alterations in the rats intoxicated with thallium.

Animals↗
PubMed2004

Modeling the ponto-medullary respiratory network.

The generation and shaping of the respiratory motor pattern are performed in the lower brainstem and involve neuronal interactions within the medulla and between the medulla and pons. A computational model of the ponto-medullary respiratory network has been developed by incorporating existing experimental data on the medullary neural circuits and possible interactions between the medulla and pons. The model reproduces a number of experimental findings concerning alterations of the respiratory pattern following various perturbations/stimulations applied to the pons and pulmonary afferents. The results of modeling support the concept that eupneic respiratory rhythm generation requires contribution of the pons whereas a gasping-like rhythm (and the rhythm observed in vitro) may be generated within the medulla and involve pacemaker-driven mechanisms localized within the medullary pre-Botzinger Complex. The model and experimental data described support the concept that during eupnea the respiration-related pontine structures control the medullary network mechanisms for respiratory phase transitions, suppress the intrinsic pacemaker-driven oscillations in the pre-BotC and provide inspiration-inhibitory and expiration-facilitatory reflexes which are independent of the pulmonary Hering-Breuer reflex but operate through the same medullary phase switching circuits.

Animals↗