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Prolongation in expiration evoked from ventrolateral pons of adult rats.

Activation of neurons in the ventrolateral (vl) pons was hypothesized to alter the breathing pattern because previous studies demonstrated apneusis after inhibiting neuronal activity with bilateral muscimol (10 mM) microinjections into the vl pons (17). The excitatory amino acid L-glutamate (10 mM) was microinjected (10-100 nl) into the vl pons in anesthetized, vagotomized, paralyzed, and ventilated adult rats (n = 8). In four of these animals, the target site was approached from the ventral surface of the pons to avoid penetrating the dorsolateral (dl) pons. The expiratory phase was prolonged transiently and concurrently with the microinjection. The location of the injection sites included the A5 area, was independent of the approach, and was distinct from the dl pons. These results complement our previous data and indicate that neurons located in the vl pons influence respiration specifically by prolonging expiration when activated and by delaying the inspiratory-to-expiratory phase transition when inhibited.

Animals↗

Vascular contact with the fifth cranial nerve at the pons in patients with trigeminal neuralgia: detection with 3D FISP imaging.

OBJECTIVE: Vascular contact with the trigeminal nerve at the pons is known to cause trigeminal neuralgia; however, this finding also is present in some asymptomatic subjects. We evaluated the usefulness of high-resolution MR imaging and MR angiography of the posterior fossa to determine the presence or absence of vascular contact with the fifth cranial nerve at the pons in patients with trigeminal neuralgia and in control subjects. SUBJECTS AND METHODS: The trigeminal nerves in 40 symptomatic patients and 114 asymptomatic control subjects were examined for the presence or absence of vascular contact at the pons by using three dimension (3D) fast inflow with steady-state precession (FISP) imaging. Imaging parameters were 35/7/15 degrees (TR/TE/flip angle) with a slab thickness of 55 mm and 64 partitions. Contrast-enhanced imaging was done in 10 of 12 patients with normal findings on an unenhanced scan. Axial, coronal, sagittal, and maximum-intensity-projection images were reviewed by two observers who had no knowledge of the clinical details. The findings on MR images were prospectively compared with the surgical findings in 25 patients. RESULTS: On the unenhanced MR images, vascular contact with the trigeminal nerve at the pons was identified in 70% of 40 nerves in patients with trigeminal neuralgia and in a further 15% following injection of contrast medium. Contact between the nerve and two vessels at the pons was seen in 10% of cases, and deformity of the nerve was present in 30% of cases. In the control group, vascular contact with the nerve was identified in 8% of 114 nerves. Contact between the nerve and two vessels or deformity of the nerve was not identified in any control subject. The difference between the two groups was highly significant regarding the presence or absence of vascular contact with the nerve at the pons (p < 0.001, x2 test), distortion of the nerve (p < .001), and contact between the nerve and two vessels (p < .001). The imaging findings were in agreement with the surgical findings regarding the presence or absence of vascular contact with the nerve in all 25 patients who had surgery. Complete or partial pain relief was achieved following microvascular decompression in all patients who had surgery. CONCLUSION: Despite the fact that vascular contact with the trigeminal nerve at the pons is not specific for trigeminal neuralgia, high-definition unenhanced and enhanced 3D FISP imaging and MR angiography at the posterior fossa are useful in determining the presence or absence of vascular contact with or deformity of, the fifth cranial nerve in patients for whom surgery is planned for treatment of trigeminal neuralgia.

Arteries↗

Age and sex differences in the cerebellum and the ventral pons: a prospective MR study of healthy adults.

BACKGROUND AND PURPOSE: The human brain exhibits a complex pattern of differential aging. The purpose of this study was to examine whether age differences in the volume of cerebellar regions and the ventral pons are differential or generalized, whether the age-related shrinkage is linear or exponential, and whether there are sex differences in the size of the cerebellum and pons. METHODS: The volumes of the cerebellar hemispheres (excluding the vermis and the peduncles), the vermis, and the ventral pons were estimated from the prospectively acquired MR scans of 190 healthy volunteers (aged 18-81 years). The relation between regional volumes, age, and sex was assessed while taking into account differences in body size (height). RESULTS: We found a moderate age-related reduction in the volume of the cerebellar hemispheres and the cerebellar vermis. In contrast to previous findings that suggested differential vulnerability of the posterior vermis, the age-related shrinkage of the vermian lobules was uniform-about 2% per decade. In accord with all reports in the literature, the size of the ventral pons was unrelated to age. The volume of the cerebellar hemispheres, the vermis, and the ventral pons were larger in men, even after adjustment for height. The magnitude of the sex difference was the largest in the hemispheres and the anterior vermis, and the smallest in the lobules VI-VII (declive-folium-tuber). CONCLUSION: Moderate age-related shrinkage of the cerebellum and lack of age-related differences in the ventral pons are robust phenomena. However, in all likelihood, the effects of age on the cerebellum are not differential but uniform. The cerebellum and the pons are larger in men than in women and the difference is especially pronounced in the cerebellar hemispheres and the anterior vermis.

Adolescent↗

Presence of C-flanking peptide of neuropeptide Y(C-PON)-immunoreactive neurons in the olfactory cortex of the hedgehog (Erinaceus europaeus).

Although the presence of the neuropeptide C-terminal flanking peptide of neuropeptide Y, C-PON, has been described in the central nervous system (CNS) of mammals, to date there is no information related with its involvement in brain functions. An analysis of the location of C-PON in specific neuronal circuits of known anatomy and physiological action should provide light on its physiological role. The presence, distribution and morphology of C-PON-containing neurons in the olfactory cortex of the hedgehog was studied by immunocytochemistry. Immunoreactive neurons to C-PON were widely distributed in the three layers of the olfactory cortex of this primitive mammal. These neurons were medium sized and showed two or three immunostained, poorly branched, dendrites. In some positive neurons, a fine, beaded axon-like process was also immunostained. Although direct evidence of a physiological function of C-PON in the olfactory cortex of the hedgehog cannot be accurately stated from our findings, the morphology of C-PON neurons and their distribution in the deep cortical layers, where the majority of pyramidal neurons are located, suggest that this neuropeptide may play a role in the intrinsic neuronal circuitry of the relatively well-developed hedgehog paleocortex. A regulatory vascular role of some peptide-immunoreactive neurons can be inferred since occasional C-PON-positive neurons have been located near blood vessels.

Animals↗

A paraoxonase gene polymorphism, PON 1 (55), as an independent risk factor for increased carotid intima-media thickness in middle-aged women.

Paraoxonase (PON) gene polymorphisms have been proposed as genetic markers of risk for cardiovascular disease (CVD). Sporadic results suggest they are correlated with intima-media thickness (IMT), an indicator of preclinical atherosclerotic disease. We have investigated whether polymorphisms PON 1 (M/L) 55, (Q/R) 192, PON 2 (S/C) 311 are related to site-specific carotid plaques in 310 middle-aged women. Subjects were also investigated for physical and biochemical parameters including oxidative markers to evaluate their effect on development of atherosclerotic plaques (IMT>1.2 mm) identified by high resolution B-mode ultrasound. We demonstrate that PON 1 (LL+ML) 55 is associated with plaques both at the bifurcation (OR=2.40; 95% CI 1.00-5.90) and at the common carotid artery (OR=2.75; 95% CI 1.01-7.50), and to the total number of plaques at any site (P<0.05). This polymorphism is an independent parameter with respect to other variables that are significantly associated with plaques, i.e. systolic blood pressure (OR=2.06; 95% CI 1.11-3.81) and oxidized low-density lipoprotein (LDL) antibodies (OR=1.96; 95% CI 1.05-3.69) in cases of common carotid plaques, and lipid peroxides (OR=1.86; 95% CI 1.00-3.50) in cases of bifurcation plaques. In conclusion, PON 1 (LL+ML) 55 but not PON 1 (Q/R) 192 or PON 2 (S/C) 311, appears to be an independent risk factor for increased carotid IMT in middle-aged women.

Adult↗

Lack of association between Alzheimer's disease and Gln-Arg 192 Q/R polymorphism of the PON-1 gene in an Italian population.

Alzheimer's disease (AD) is characterized by deposition of oxidized low-density lipoprotein (LDL) forming the senile plaque and by structural changes and cell death in acetylcholine-producing neurons. Paraoxonase-1 (PON-1) is a secreted protein primarily associated with high-density lipoproteins (HDL) and participates in the prevention of LDL oxidation. PON-1 is also an arylesterase that hydrolyzes paraoxon, an active toxic metabolite of parathion, thus providing protection against organophosphate poisoning and metabolization of environmental neurotoxins that might be responsible for neurodegeneration with aging. Serum levels of PON-1 are genetically determined and strongly influenced by a common polymorphism on the position 192 of the PON-1 gene. The aim of this study was to evaluate whether the polymorphism of the PON-1 gene is associated with AD. We studied 124 Italian subjects affected by probable AD and 135 age- and sex-matched controls. The distribution of PON-1 genotypes was 64 QQ, 46 QR, 14 RR in the AD patients and 57 QQ, 59 QR, 19 RR in the control subjects. No statistically significant difference was found between the two groups in our population (p = 0.130 for homozygous QQ, p = 0.279 for heterozygous QR, and p = 0.502 for homozygous RR). These results suggest that the human Gln-Arg 192 Q/R polymorphism of the PON-1 gene is not associated with AD in an Italian population.

Aged↗

Cardiovascular and muscle tone changes produced by microinjection of cholinergic and glutamatergic agonists in dorsolateral pons and medial medulla.

Cardiovascular and muscle responses to L-glutamic acid (Glut) and cholinergic agonists injected into the dorsolateral pontine tegmentum and medial medullary reticular formation (MMRF) were examined in unanesthetized, decerebrated cats. Glut, or cholinergic agonists acetylcholine (ACh) or carbachol (Carb), were injected into pons and MMRF at sites from which electrical stimulation produced bilateral suppression of muscle tone. Glut injection in MMRF produced hypotension without change in heart rate at doses as low as 1 mM. At higher doses (0.1-0.4 M), Glut induced hypotension with bradycardia in 23 out of 40 injections in both pons and MMRF. High concentrations of microinjected Glut decreased muscle tone or produced complete atonia in pons and rostral MMRF. Both N-methyl-D-aspartic acid (NMDA) and non-NMDA receptor blockers attenuated or completely blocked the cardiovascular response, while only non-NMDA antagonists blocked muscle inhibition to Glut injection. Microinjection of cholinergic agonists produced consistent hypotension in all of the injections in pons and MMRF, however, the heart rate response was variable with increase (27/42), decrease (2/42), or no change (13/42) in rate seen. Cholinergic injection produced muscle atonia in pons and caudal MMRF but not in rostral MMRF. Both muscle and cardiovascular responses were blocked by atropine but not by hexamethonium. The time course of muscle atonia and cardiovascular change differed in most of the experiments. We conclude that muscle tone suppression and cardiovascular response to Glut or cholinergic agonists use different receptor mechanisms and possibly different neurons. However, the co-localization of these mechanisms suggests that neuronal networks in the medial medulla and dorsolateral pons coordinate motor and cardiovascular responses.

Animals↗

In vivo pons motion within the skull.

Finite element (FE) models are used to identify head injury mechanisms and design new and improved injury prevention schemes. Although brain-skull boundary conditions strongly influence the model mechanical responses, limited experimental data are available to develop an informed representation. We hypothesize that the spinal cord tension and gravity contribute to the pons displacement in vivo. Static high-resolution T1-weighted sagittal MR images of the inferior portion of the head in neutral and flexion positions were acquired in 15 human volunteers in both supine and prone postures. Boundaries of the pons and clivus were extracted with a gradient-based algorithm, and the pontes were fitted into ellipses. Assuming rigid body motion of the skull, image pairs in different postures were co-registered with an autocorrelation technique. By comparing images before and after the motion, we found that while the rotation of the pons is negligible relative to the skull, the pons displaces significantly at the foramen magnum, on the order of approximately 2 mm. When the spinal cord tension and gravity act in concert, the pons moves caudally; when opposed, superiorly, such that the influence of gravity on the pons is six times that of the spinal cord tension. Based on these findings, we recommend that the brainstem-skull interface be treated as a sliding (with or without friction) boundary condition in FE models of the human head.

Adult↗

Localization and properties of respiratory neurons in the rostral pons of the newborn rat.

The distribution and discharge pattern of respiratory neurons in the 'pneumotaxic center' of the rostral pons in the rat has remained unknown. We performed optical recordings and whole-cell patch clamp recordings to clarify respiratory neuron activity in the rostral pons of a brainstem-spinal cord preparation from a newborn rat. Inspiratory nerve activity was recorded in the 4th cervical nerve and used as a trigger signal for optical recordings. Respiratory neuron activity was detected in the limited region of the rostral-lateral pons. The main active region was presumed to be primarily the Kölliker-Fuse nucleus. The location of respiratory neurons was further confirmed by Lucifer Yellow staining after conducting whole-cell recordings. From a membrane potential analysis of the respiratory neurons in the rostral pons, the respiratory neurons were divided into four types: inspiratory neuron (71.9%), pre-inspiratory neuron (5.3%), post-inspiratory neuron (19.3%), and expiratory neuron (3.5%). A noticeable difference between pontine and medullary respiratory neurons was that post-inspiratory neurons were more frequently encountered in the pons. Application of a mu-opioid agonist, [d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin, transformed the burst pattern of post-inspiratory neurons into that of pre-inspiratory neurons. The electrical stimulation of the sensory root of the trigeminal nerve induced three types of responses in 85% of pontine respiratory neurons: inhibitory postsynaptic potentials (42.7%), excitatory postsynaptic potentials (37.7%) and no response (15.1%). Our findings provide the first evidence in the rat for the presence of respiratory neurons in the rostral pons, with localization in the lateral region approximately overlapping with the Kölliker-Fuse nucleus.

Animals↗

The human startle reflex and pons activation: a regional cerebral blood flow study.

Using positron emission tomographic measurements of regional cerebral blood flow, we report activation of a medial pons area in humans during acoustic startle stimulation. Eight healthy volunteers were scanned during rest and when presented startle-eliciting stimuli. We performed a theory-driven directed search for activity in the nucleus reticularis pontis caudalis, situated in the pons. Because habituation of cerebellar activity during acoustic startle repetition has been reported [Timmann, D., Musso, C., Kolb, F.P., Rijntjes, M., Juptner, M., Muller, S.P., Diener, H.C. & Weiller, C. (1998) J. Neurol. Neurosurg. Psychiatry 65, 771-773], we also predicted habituation in the cerebellum and in the pons as a function of startle repetition. Measurements of eye electromyography validated the presence of a startle response and its habituation. Analysis of regional cerebral blood flow revealed higher neural activity during startle stimulation than at rest in a medial pons area consistent with the location of the pontine reticular nucleus. As a consequence of startle repetition, regional cerebral blood flow increased in the medial cerebellum, and habituated in the ventral cerebellum and in a ventral pons area separate from the pontine reticular nucleus. In the ventral pons, but not in the pontine reticular nucleus, regional cerebral blood flow and the startle reflex were positively correlated. In the cerebellum both positive and negative correlations with the startle reflex were observed. Thus we conclude that the neurofunctional correlates of the startle circuit and its habituation in humans are similar to that previously described in animals.

Adult↗

Neurones in the ventrolateral pons are required for post-hypoxic frequency decline in rats.

1. The breathing pattern following acute hypoxia (arterial O2 pressure (Pa,O2), 27.4 +/- 7.7 mmHg) was measured in intact, anaesthetized and spontaneously breathing adult rats (n = 4) and in anaesthetized, vagotomized, paralysed and ventilated animals (n = 14). Measurements were made both before and after bilateral lesions or chemical inactivation of neurones in the lateral pons. Respiratory motor activity was recorded as an index of the respiratory cycle. We tested the hypothesis that the ventrolateral pons is required for expression of post-hypoxic frequency decline, defined as a decrease in respiratory frequency below steady-state baseline levels following brief exposures to hypoxia. 2. We identified an area in the ventrolateral pons where brief (1 ms) low current (< or = 20 microA) pulses evoked a short-latency inhibitor of phrenic nerve activity. At this site, bilateral electrical or chemical lesions (n = 3) were performed, or neural activity was inhibited by focal injections of 10 mM muscimol (n = 9). In six control animals, neural activity was inhibited by muscimol injections into the lateral pons, dorsal to the target site. 3. Prior to pontine intervention, respiratory frequency decreased below baseline levels following 20-110 s of 8% O2. The decrease in frequency resulted from a prolongation of expiration (up to 276%), which gradually returned to baseline levels (tau = 45 s). 4. Following lesions or inhibition of neural activity in the ventrolateral pons, baseline inspiratory (TI) and expiratory (TE) durations were altered, albeit minimally, in the animals with intact vagus nerves. Expiratory duration following hypoxia was not different from baseline levels either in vagotomized (P = 0.18) or intact (P > 0.05) animals. In contrast, injections of muscimol at more dorsal sites did not alter the decrease in frequency normally seen following hypoxia. 5. Histological examination revealed that effective lesion or injection sites were within the lateral pontine tegmental field and included portions of the noradrenergic A5 cell group. 6. We conclude that the mechanism responsible for post-hypoxic frequency decline involves an active neural process that depends on the integrity of the ventrolateral pons.

Animals↗

[Morphometry of the brainstem with transverse section of the upper pons].

The authors developed new method of morphometry in the brainstem, which used transverse section of the upper pons. After fixation with formalin, the brainstem was separated from the cerebrum and the cerebellum. Both junctions of midbrain-pons and pons-medulla were cut and then the pons was horizontally separated into four slices. The oral surface of the second slice from oral side, in which the central portion of the locus ceruleus is located, was measured with computed digitizer after enlarging the picture. The authors measured the total size of the slice in the pons (Total S), the tegmentum size (Teg S), the total length (Total L), the tegmentum length (Teg L) and so on. The tegmentum was separated from the base along the ventral line of the medial leminiscus. In the study of 23 control cases (16 to 77 year old, 13 male and 10 female, all were Japanese), Total S (563 +/- 85 mm) and Teg S (136 +/- 19 mm) ranged to some extent, while the percentage of the tegmentum size to the total size (Teg S/Total S X 100: %Teg S) distributed in narrow range (24.4 +/- 2.3%), which was considered to be an appropriate index to reveal normal structure of the upper pons. The percentage of the tegmentum length to the total length (%Teg L) was also an appropriate and a simple index. Using this method to stained preparation, it was confirmed that the tegmentum size of such cases with olivopontocerebellar atrophy or infantile spasms were significantly small.

Adolescent↗

[Predominantly ipsilateral smooth pursuit impairment associated with a lesion in the basal pons].

In contrast to the well-defined brainstem centers for saccades and eye reflexes, the brainstem centers mediating smooth pursuit eye movements are poorly understood. In monkeys, unilateral damage to the basal pons impairs horizontal smooth pursuit in the direction of the side of the lesion. The major source of afferents to the basal pons is the middle temporal area (MT). The dorsolateral pontine nucleus (DLPN) in the basal pons is considered to be the major gateway for smooth pursuit related signals to the contralateral flocculus. In humans, only one patient was found to have a unilateral lesion in the basal pons and selective impairment of smooth pursuit toward the side of the lesion. We report a 34-year-old man with a lesion in the basal pons identified by MRI. He had suffered from recurrent oral aphthosis, erythema nodosum and enterocolitis, and was hospitalized because of dysarthria. He was clinically diagnosed as neuro-Behçet disease. Saccades, smooth pursuit, vestibulo-ocular reflex (VOR), and VOR cancellation were measured. Ipsilateral smooth pursuit eye movements were predominantly impaired and interrupted by saccades, whereas VOR cancellation was impaired in both directions, in contrast with normal saccades and VOR. This observation of predominantly ipsilateral smooth pursuit impairment after a lesion in the human basal pons suggests that the concept of a middle temporal-ponto-floccular pathway for smooth pursuit, previously established in monkeys, can be extended to humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Relationship between muscarinic receptor subtypes and cyclic nucleotides in pons-medulla oblongata.

AIM: To study the relationship between muscarinic receptor (M-R) subtypes and cyclic nucleotides in pons-medulla oblongata (MeOb). METHODS: The contents of cGMP and cAMP in Sprague-Dawley rat pons-MeOb, cerebellum and cerebral cortex were assayed by radioimmunoassay and competitive protein-binding assay, respectively, after ip injections of drugs. Control rats were given ip normal saline. RESULTS: M1-R agonist pilocarpine (6, 15 mg kg-1, ip) increased the content of cGMP in the pons-MeOb and cerebral cortex, but did not bring about any noticeable change in the cAMP content. The increase of cGMP was antagonized by ip pirenzepine or scopolamine. On the other hand, ip M2-R agonist 6 beta-acetoxy nortropane (6 beta-AN) 25 micrograms kg-1 reduced not only cAMP contents in the pons-MeOb and cerebellum but also cGMP contents in the pons-MeOb and cerebral cortex, while 6 beta-AN 12 micrograms kg-1 only lowered cAMP content. The decreases of cGMP and cAMP induced by 6 beta-AN were antagonized by ip AF-DX 116 or atropine, respectively. CONCLUSION: Stimulation of M1-R causes the increase of cGMP and that of M2-R induces the decreases of both cGMP and cAMP in the pons-MeOb.

Animals↗

The Gln/Arg polymorphism of human paraoxonase (PON 192) is not related to myocardial infarction in the ECTIM Study.

Paraoxonase is a high-density-lipoprotein associated enzyme capable of hydrolyzing lipid peroxides, which has been suggested to contribute to atherosclerosis and coronary heart disease (CHD). We studied the Gln/Arg polymorphism affecting codon 192 of human paraoxonase (PON 192) to determine whether this polymorphism, which is associated with serum paraoxonase (PON) activity, represents a risk factor for myocardial infarction (MI). The PON 192 polymorphism was analysed in 642 male patients with myocardial infarction and 701 age-matched controls participating in the ECTIM Study (Etude Cas-Témoins de l'Infarctus du Myocarde). The frequency of the Gln allele was 0.69 in cases and 0.70 in controls (ns). The frequency of the PON 192/Arg allele in 405 MI patients who underwent coronary angiography was 0.295, 0.323 and 0.331, respectively in those with 1, 2 or 3 stenosed arteries (stenosis > 50%) (ns). The mean levels of several plasma lipids, lipoproteins and apolipoproteins were compared between the 3 PON genotypes and no difference was observed. The PON 192 polymorphism was unrelated to MI, the severity of coronary atherosclerosis and to plasma levels of several lipid variables.

Adult↗

Identification of candidate genes for controlling development of the basilar pons by differential display PCR.

The basilar pons, a major hindbrain nucleus involved in sensory-motor integration, has become a model system for studying long-distance neuronal migration, axon-target recognition by collateral branching, and the formation of patterned axonal projections. To identify genes potentially involved in these developmental events, we have performed a differential display PCR screen comparing RNA isolated from the developing basilar pons with RNA obtained from developing cerebellum and olfactory bulb, as well as the mature basilar pons. Using 400 different combinations of primers, we screened more than 11,000 labeled DNA fragments and identified 201 that exhibited higher expression in the basilar pons than in the control tissues. From these, 138 distinct gene fragments were cloned. The differential expression of a large subset of these fragments was confirmed using RNase protection assays. In situ hybridization analysis revealed that the expression of many of these genes is limited to the basilar pons and only a few other brain regions, suggesting that they may play specific roles in pontine development.

Animals↗

MRI measurements of the pons and cerebellum in children born preterm; associations with the severity of periventricular leukomalacia and perinatal risk factors.

Our purpose was to measure the size of the pons and cerebellum in preterm babies with periventricular leukomalacia (PVL), and to study their relationship with the severity of PVL and with perinatal risk factors. We examined 33 premature children, mean gestational age 31 weeks, range 26-36 weeks with PVL on MRI, and 27 full-term controls. On MRI at 0.4-5.5 years (mean 1.4 years) we measured the area of the corpus callosum and vermis, the anteroposterior diameter of the pons and the volume of the cerebellum. The area of the corpus callosum was used as a marker of white matter loss and PVL severity. All regional brain measurements except that of the vermis were significantly lower in patients than controls: corpus callosum (mm(2)): 239.6+/-92.5 vs 434.8+/-126.8, P <0.01; pons (mm): 14.8+/-3.0 vs 17.9+/-1.4, P <0.01]; cerebellum (cm(3)): 68.2+/-31.6 vs 100.6+/-28.3, P <0.01; vermis (mm(2)): 808.1+/-292.2 vs 942.2+/-246.2, NS. Significant reduction in the area of the vermis: 411.3+/-203.3 vs 935+/-252.6 mm(2); cerebellar volume: 16.3+/-12.5 vs 96.6+/-20.2 mm(3); and the diameter of the pons: 10.1+/-2.2 vs 17.5+/-1.3 mm ( P<0.01) were observed in seven children with gestational age < or =28 weeks, severe hypotension and large patent ductus arteriosus (PDA). There was a significant correlation between the duration of mechanical ventilation and the size of the vermis, pons and cerebellum (R=-0.65, -0.57 and -0.73, respectively, P <0.01).

Case-Control Studies↗

Glutamate immunoreactivity in the rat basilar pons: light and electron microscopy reveals labeled boutons and cells of origin of afferent projections.

Immunohistochemical methods that employed a polyclonal antiserum directed against a glutamate-hemocyanin conjugate were utilized to examine the rat basilar pontine nuclei at both light and electron microscopic levels in order to identify putative glutamatergic neural elements. A large number of cells ranging in size from 11 to 32 microns in diameter and present in all subdivisions and at all rostrocaudal levels of the basilar pons exhibited intense glutamate immunoreactivity. Immunoreactive punctate structures, confirmed by electron microscopy to be axon terminals, were homogeneously distributed throughout the pontine neuropil, although a somewhat greater accumulation was apparent medially at mid-levels of the basilar pons and laterally at more caudal levels. Immunolabeled axons were also present throughout the pontine nuclei. In order to demonstrate possible extrinsic sources of glutamate-immunoreactive axon terminals within the pontine gray, injections of wheat germ agglutinin-horseradish peroxidase were made directly into the basilar pons. Tissue was then evaluated for the presence of retrogradely transported wheat germ agglutinin-horseradish peroxidase and the same tissue sections processed for glutamate immunocytochemistry. Following this combined protocol, neuronal somata exhibiting both wheat germ agglutinin-horseradish peroxidase and glutamate immunoperoxidase reaction products were observed within layer Vb of the cerebral cortex, zona incerta, the dentate nucleus of the cerebellum, nucleus paragigantocellularis of the medullary reticular formation, and the dorsal column nuclei. Such double-labeled cells were considered to represent glutamatergic neurons that provide axonal projections to the basilar pons. Ultrastructural studies of the pontine nuclei confirmed the presence of glutamate immunogold labeling in dendrites, neuronal somata, axons, and axon terminals. Immunoreactive boutons contained round vesicles and primarily formed asymmetric synapses at various postsynaptic loci which included glutamate-immunolabeled dendritic profiles and somata. These results suggest that glutamatergic basilar pontine neurons form one segment of a multisynaptic pathway involving glutamatergic afferents to the basilar pons, glutamatergic pontocerebellar projection neurons, and the glutamatergic granule cells of the cerebellar cortex.

Afferent Pathways↗