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The effect of chronic aluminum(III) administration on the nervous system of aged rats: clues to understand its suggested role in Alzheimer's disease.

The effect of chronic aluminum intake has been investigated in the brain of aged male Wistar rats to assess the potential role of the accumulation of this metal ion on the development of neurodegenerative features observed in Alzheimer's disease. AlCl3 x 6 H2O (2g/L) was administered to experimental animals for 6 months in the drinking water. The total content of Al (microg/g fresh tissue) was measured by inductively coupled plasma atomic emission spectrometry (ICP-AES), while the content of Cu, Zn and Mn was determined by flame AAS in the prosencephalon + mesencephalon, pons-medulla and cerebellum of control and Al(III)-treated animals. The area occupied by mossy fibres in the CA3 field of the hippocampus was estimated by a computer-assisted morphometric method following Timm's preferential staining. In Al(III)-treated rats the concentration of Cu, Zn and Mn did not increase significantly (p < 0.5) in prosencephalon + mesencephalon, nor in pons-medulla (p < 0.5) except for Cu (p < 0.05) in pons-medulla. In the cerebellum the only significant increase was seen for Zn (p < 0.01) while no change was observed for Cu and Mn. The area occupied by the mossy fibres in the hippocampal CA3 field was significantly increased (+32%) in aged Al(III)-treated rats. Since Cu, Zn and Mn are essential components of the cytosolic and mitochondrial superoxide dismutases, it is possible that the increased content of these ions in aged Al(III)-treated rats represents an increased amount of genetic expression of these antioxidant enzymes. Considering that the positivity to Timm's reaction is based on the presence of free or loosely bound Zn2+ ions within synaptic terminals and that Zn2+ ions are reported to be accumulated by hippocampal neurons when tissue injury occurs, the increased area of the mossy fibres in CA3 field of Al(III)-treated rats could indicate increased hippocampal damage in these animals. Taken together, the present findings indicate that the aging CNS is particularly susceptible to Al(III) toxic effects which may increase the cell load of oxidative stress and may contribute, as an aggravating factor, to the development of neurodegenerative events as observed in Alzheimer's disease.

Aggression↗

On pure motor hemiplegia (Fisher's syndrome).

The authors described three cases of so-called "lacunar strokes" with pure motor hemiplegia. Clinical diagnosis in all three cases was middle cerebral artery thrombosis. In cases 1 and 2 small post-malacic lacunes were found in the basal part of the pons. In case 3 the lesion was located in the pyramidal tract within the pons and medulla. In all cases advanced arteriosclerotic changes were observed. "Lacunar stroke" can result from a lesion of both the pons and the medulla. The clinical syndrome may be engendered also by selective lesion of the pyramidal tract.

Aged↗

Effects of acute and chronic ethanol administration and withdrawal on adenosine 3':5'-monophosphate and guanosine 3':5'-monophosphate levels in the rat brain.

The effect of ethanol on cyclic nucleotide levels was investigated in male Sprague-Dawley rats. The rats were sacrificed by microwave irradiation, the brains were divided into four areas, and cyclic nucleotides were measured by radioimmunoassays. Administration of a single dose of ethanol per os produced a dose-dependent decrease of adenosine 3':5'-monophosphate (cyclic AMP) in cerebral cortex, cerebellum, pons and medulla oblongata while guanosine 3':5'-monophosphate (cyclic GMP) was decreased in all brain areas. Dependence on ethanol was induced by three daily administrations of ethanol p.o. for 7 days. The last dose of ethanol did not produce any decrease of cyclic AMP levels while the decrease of cyclic GMP levels was still present. During ethanol withdrawal cyclic AMP levels increased in cerebral cortex, pons and medulla oblongata and did not change in cerebellum. Changes of cyclic AMP in subcortex were more complex. Cyclic GMP levels increased during ethanol withdrawal in cerebellum, pons and medulla oblongata and did not change in cerebral cortex and subcortex. These results indicate that changes of cyclic nucleotides might participate in the mechanism of ethanol dependence and withdrawal.

Animals↗

Neurochemical changes in the brain and spinal cord of sheep: a basis for the immobilizing action of etorphine.

Clinical and pharmacological analyses showed a full immobilizing action of etorphine in adult sheep +/- 7 min. after a deep i.m. injection of the drug at a dosage rate of 20 micrograms/kg. Neurochemical analyses of motoric CNS-structures done within 30 min. after i.m. injection of etorphine in an immobilizing dose, showed the following: A significant decrease of dopamine (DA) and homovanilic acid (HVA) concentrations in the corpus striatum, the frontal motor cortex, cerebellum and in the lumbo-sacral portion of the spinal cord. A decrease of DA-concentration with a simultaneous increase of HVA-concentration in the pons. A significant decrease of noradrenaline (NA) concentration in the cerebellum and lumbo-sacral portion of the spinal cord and an insignificant decrease of amine concentration in the pons. A significant increase of adrenaline (A) concentration in the frontal motor cortex. A significant decrease of 5-hydroxytryptamine (5-HT) concentration in the frontal motor cortex and cerebellum and an equally significant increase in its concentration in the pons.

Animals↗

A functional viewpoint on paradoxical sleep-related brain regions.

Slow wave sleep is a condition for paradoxical sleep (PS) expression. The lower brain stem is able to produce the known PS phenomena but, in order to do so in all its functional magnitude, it depends on the rest of the brain. There are physiological conditions that appear as necessary to develop the PS. A group of basic functions, i.e., respiration, cardiovascular, brain oxygen availability, temperature, etc., have to go on in a non-homeostatic fashion during this state. Other conditions to be met are: the cut-off of the motor output and a different central control of the sensory input. During PS, phasic pO2 changes were observed in some nuclear structures characterized by a dramatic increase in the amplitude of oscillations. These changes were found in a number of subcortical, cerebellar and brain stem regions and were never observed neither in the neocortex, the specific thalamic nuclei nor in the white matter. It is postulated that these variations are due to a local increase in neuronal activity in PS during a decrease of the local homeostatic oxygen control. All the physiological changes above mentioned have a common anatomical denominator: the pons and medulla. Upon this region, proposed as the PS FINAL COMMON REGION, conveges rostral and caudal information making it the executor of all PS phenomena. The pons, on the other hand, has a bioelectrical activity of its own during PS, i.e., the ponto-geniculo-occipital spikes (PGO). This activity spreads through the brain and cerebellum. The cerebellum also participates in sleep physiology: the pO2 oscillations pattern and PGO are present in all of its parts, cortex and nuclei, being, the spike activity, dependent of a cholinergic pontine region. The pons shows a particular duality during PS. It is part of the FINAL COMMON REGION for PS phenomena and, at the same time, it is the origin of the PGO activity.

Animals↗

[Magnetic resonance imaging in spinocerebellar degeneration].

Magnetic resonance imaging (MRI) was evaluated in 11 patients with non-familial spinocerebellar degeneration (6 olivo-ponto-cerebellar atrophy (OPCA) and 5 late cortical cerebellar atrophy (LCCA]. MRI was carried out using a superconducting magnet of 0.256 tesla (VISTA-MR) and an inversion recovery pulse sequence of repetition time 2.08 sec and inversion time 0.5 sec. The degree of atrophy was assessed with regard to ponto-cerebellar system (basis pontis and middle cerebellar peduncle) and cerebellum in the sagittal and coronal images. In the mid-sagittal images, the width of ventral pons, dorsal pons, tegmentum and tectum of midbrain, and the height of fourth ventricle were measured. Especially, the degrees of atrophy of basis pontis in the mid-sagittal image and middle cerebellar peduncle in the coronal image were divided into 4 grades and evaluated respectively. On the other hand, atrophy of cerebellum was judged from enlargement of cerebellar fissures and reduction of cerebellar volume in the sagittal and coronal images. Atrophy of ponto-cerebellar system was found in OPCA, but not in LCCA. In OPCA, atrophy of middle cerebellar peduncle in the coronal image, which was likely to begin in an inferior part of pons, was more marked than, or equal to, atrophy of basis pontis in the mid-sagittal image. With regard to cerebellar vermis, the superior faces were more atrophic than the inferior faces in both OPCA and LCCA, but in OPCA, atrophy on the superior faces was dominant in the posterior lobe including declive and folium as against dominance in the anterior lobe in LCCA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Clinicopathological studies of diffuse axonal injury--five autopsy cases].

In severe head injuries, delayed intracerebral hematoma appearing lately is noted due to the spread use of serial CT scan. The authors experienced the autopsy of 5 cases who presented diffuse axonal injury (DAI) among these new lesions in repeated CT scan findings and report the pathohistological findings. Subjects were as follows: The age range of the patients was 15 to 25 years. The consciousness levels of the 5 cases on admission were 6 or less by the Glasgow coma scale. CT findings of DAI were revealed hemorrhage of the corpus callosum, basal ganglia, tegmentum of pons, intraventricular, and acute brain swelling. Total clinical courses were 2 to 29 days, but most of them were 9 or less days. In the macroscopic findings, marked congestion and edema revealed mainly in deep part of the white matter of the frontal lobe in all 5 cases. Callosal disruption and hematoma adjacent the corpus callosum revealed in 4 out of 5 cases. Cerebral contusion with hemorrhage revealed in 3 out of 5 cases. Intraventricular hemorrhage and traumatic subarachnoid hemorrhage revealed in 2 out of 5 cases. Hemorrhage of basal ganglia and base of pons revealed in 2 cases. Microscopic examination of all 5 cases revealed pallor of myelin in the corpus callosum and white matter surrounding hemorrhagic lesion, and abnormal tortuous, swelling and fragmentation of axons in stained preparation. Axonal retraction ball was recognized in 3 out of 5 cases. In conclusion, five autopsied cases who presented acute brain swelling and hemorrhage of corpus callosum and tegmentum of pons in serial CT scan were examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Serotonin levels and turnover in different brain areas of isolated aggressive or non-aggressive strains of mice.

After eight weeks of individual housing DBA/2 but not C57 B1/6 (C57) mice showed high levels of aggressive responses in comparison with grouped mice. Social isolation did not modify serotonin (5-HT) levels in either strain of mice, while it produced a decrease of turnover rate in amygdala, lateral hypothalamus and pons in C57 mice and in lateral hypothalamus and pons of DBA mice. When isolated mice of both C57 and DBA strains are compared, no differences in turnover rate in amygdala and pons are evident, while isolated DBA mice show significant lower turnover values in lateral hypothalamus in comparison with isolated C57 mice. A possible suggestion emerging from our results is that aggressive responses exhibited by isolated DBA mice but not by isolated C57 mice may be related to lower 5-HT turnover rate in lateral hypothalamus.

Aggression↗

[Convergence of corticofugal impulses on pontine neurons].

The convergence of corticofugal impulses in reticular and grisea pontis nuclei evoked by stimulation of the neocortex frontobasal regions (proreal, posterior orbital, basal temporal) as well as of the dorsal hippocampus was studied in cats narcotized by a mixture of nembutale and chloralose. Three foci of corticofugal impulse convergence were determined in the structures of pons varolii: one in the reticular formation and two in grisea pontis nuclei -- in their medial and lateral regions. Neurons with excitatory reactions are shown to dominate in the pons varolii reticular formation and those with inhibitory and mixed reactions -- in the grisea pontis. The integrative function of pons varolii nuclei in the functional connection of frontobasal zones of neocortex and hippocampus is discussed.

Animals↗

[Comparative studies of rhombencephalon vascularization in rabbit and man in light of anatomic and microangiographic studies].

A comparative study of a microvascularization of the rhombencephalon, especially pre- and capillary system, in rabbits and in humans was performed. It was intended to find out whether there were any similarities and differences in rhombencephalon microvascularization of a rabbit and man. The study was carried out on 75 (50--female, 25--male) mixed-race rabbits aged 4 months, as well as on 30 (15--females, 10--males) human brains that had been dissected free from cadavers, aged from 20 up to 70 years. Angiography of sections of the rhombencephalon in rabbits and cadavers was performed. The vessels were investigated after the introduction of Micropaque contrast medium, under controlled pressure, into an investigated vessel. Intravital injection of the contrast into rabbit's vessel was beneficial for the experiment. Radiography of intact brains as well as sections of the frontal plane was accomplished. Large arterial vessels were measured, with the results being subjected to statistical analysis (Table 1-2, Fig. 1-7). Microvascularization of the medulla oblongata and of the pons in rabbits were similar to those in its human counterparts, whereas the vascular system of the cerebellum was different. The results of micrographic studies were not always the same as described by Bochenek et al. The anatomical forms that had not been previously described were noted: para--medial arteries to the medulla oblongata and the pons; lateral arteries to the medulla oblongata and the pons; posterior arteries to the medulla oblongata; branches of the upper artery of the cerebellum branching and the simple ones with few lateral branches. The central or medial artery that follows the central sulcus was separate.

Adult↗

[Electrophysiologic analysis of cortico-pontine relationships].

Projections of different regions of orbitofrontal and basotemporal cortex as well as of the hippocampus in the pons varolii area were studied by means of focal recording in acute experiments on cats anesthetized with nembutal and chloralose. It is shown that different formations of the frontobasal regions of the neocortex have local projections into the rostral zones of pons varolii and relatively diffuse projections into its caudal regions. The representation of the hippocampus is weaker as compared with the representation of the frontobasal region, and the focal responses are more diffuse. All the studied structures are represented in the nuclei of the pons varolii. The region of the orbitofrontal cortex is not represented in the caudal part of the reticular formation, the basotemporal cortex has no projections into brachium pontis.

Animals↗

[A case of basilar artery occlusion associated with one-and-a-half syndrome, paralytic pontine exotropia and WEBINO-syndrome].

We report a 79-year-old woman with basilar artery occlusion. She had a sudden onset of tetraplegia and disturbed consciousness, and within four days from the onset she showed a varied, fluctuating eye symptoms. On admission, she showed ocular bobbing, skew deviation with the right eye lower-positioned, upward gaze palsy, one-and-a-half syndrome, and paralytic pontine exotropia (PPE). On the third day after the onset, she showed wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) syndrome, and on the fourth day, she showed one-and-a-half syndrome again. Her right-gaze palsy improved repeatedly, and on the 19th day from the onset, only right MLF syndrome remained. Her eye symptoms fluctuated probably according to the distal migration of emboli, there by the responsible lesion and the mechanism of these eye symptoms are considered to be closely inter-correlated. On the fourth day after onset, the magnetic resonance imaging revealed cerebral infarctions in bilateral middle pons, the left paramedian lower pons, and the right paramedian midbrain, and a hemorrhagic infarction in the right inferior cerebellar hemisphere. We believe that that the eye symptoms of this patient were caused by lesions in the paramedian midbrain or pons.

Aged↗

Differential effects of age and sex on the cerebellar hemispheres and the vermis: a prospective MR study.

PURPOSE: The purpose of this study was to determine the effects of age and sex on the size of the cerebellar hemispheres, the cerebellar vermis, and the pons in healthy adults. METHODS: We estimated the volumes of the cerebellar hemispheres (excluding the vermis and the peduncles), the cross-sectional area of the vermis, and the cross-sectional area of the ventral pons from MR images obtained in 146 healthy volunteers, 18 to 77 years old. RESULTS: We found a mild but significant age-related reduction in the volume of the cerebellar hemispheres and in the total area of the cerebellar vermis; however, the analysis of age trends in the vermian lobules revealed differential age-related declines. The areas of lobules VI and VII and of the posterior vermian lobules (VIII-X) declined significantly with age, whereas the anterior vermis (I-V) showed no significant age-related shrinkage. The volume of the cerebellar hemispheres (especially the right) and the area of the anterior vermis were greater in men, even after adjustment for height. Neither age nor sex affected the area of the ventral pons. CONCLUSIONS: Normal aging of the cerebellum is associated with selective regional shrinkage. The cerebellar hemispheres and the area of the anterior vermis may be larger in men than in women regardless of differences in body size.

Adolescent↗

Identifying mRNAs involved potentially in corticopontine projection by modified differential display.

The basilar pons plays an important role in the establishment of the corticopontine projection by releasing a diffusible molecule which induces and directs collateral branchings along the corticospinal axon shafts. To reveal the molecule which is involved in the developing process of the corticopontine projection, we attempted to modify the mRNA differential display to search for genes expressed differentially in the basilar pons during the formation of the corticopontine projection by introducing the RGD motif (arginine-glycine-asparate) in the primers of the polymerase chain reaction. With our modification, we were able to identify 99 mRNAs expressed in the basilar pons but not in the cerebral cortex where the apparent pontine-derived activity is not observed. Among these 99 gene fragments, 3 novel fragments could be selected as final candidates of the pontine-derived molecule based on their expression patterns. Modified differential display is thus a promising method for identification of these genes.

Animals↗

Anatomical study of vestibulospinal neurons in lampreys.

The present study was carried out to characterize anatomically the vestibulospinal (VS) system of lampreys. Cobalt-lysine or Texas Red dextran amines were applied in vitro to the rostral spinal cord. Two distinct populations of VS neurons were labeled in the ventral nucleus of the area octavolateralis. The rostral group, comprising the intermediate octavomotor nucleus (ION), contained between 100 and 150 neurons, having somata of variable size and morphology. Intracellular injections of Lucifer Yellow in single neurons revealed ION VS neurons with dendrites extending in the ventrolateral alar plate as well as medially in the basal plate. The caudal group, comprising the posterior octavomotor nucleus (PON), contained approximately 65 neurons, most of which were unipolar with round or oval somata. To study the projections of VS axons, cobalt-lysine was injected into the ION or PON regions in the brainstem. Axons from the ION projected to the ipsilateral spinal cord, whereas PON axons decussated within the basal plate giving out descending and ascending branches. The descending branch projected to the contralateral spinal cord. Injections of two fluorescent dextran-amines, each restricted to one side of the spinal cord, did not double-label VS cells in either octavomotor nuclei, indicating that the projections of each nucleus are restricted to one side. Injections of horseradish peroxidase further caudally in the spinal cord revealed that VS axons from the ION reached past the gill region. Our results indicate that the organization of the VS system of lampreys is similar to that observed in other vertebrates.

Animals↗

Prognostic factors and results of therapy for adult thalamic and brainstem tumors.

This report is a retrospective analysis of 83 adults (greater than 16 years of age) with histologically proven or presumed primary neoplasms of the thalamus, hypothalamus, midbrain, pons, and medulla. Patients were treated with combined surgery and postoperative irradiation or with irradiation alone at the Washington University Medical Center (St. Louis, MO) from January 1950 through December 1984. Histologic analysis confirmed the diagnosis of tumor in 21, including nine with well-differentiated astrocytoma, four with astrocytoma with anaplasia, and eight with glioblastoma multiforme. Overall and disease-free survivals at 5 years were 28.7 and 23.2%, respectively. A statistical analysis was performed to ascertain the prognostic importance of the following variables: age, race, gender, duration of symptoms, cranial nerve paresis, primary site, extent of surgery, histology, and irradiation dose. The only factor identified by univariate analysis to be critical for survival was primary location of disease. Patients with supratentorial (thalamus/hypothalamus, midbrain) tumors had a 10-year disease-free survival of 15.4% compared to 29.6% for those with infratentorial (pons, medulla) tumors (P = 0.07). Patients with lesions of the pons had a 5-year disease-free survival of 35.8% compared to 13.8% for those with tumors of the thalamus (P = 0.05). Increasing irradiation dose was not correlated with superior survival. Factors evaluated but established to be insignificant were age (P = 0.27), race (P = 0.63), gender (P = 0.27), duration of symptoms (P = 0.19), cranial nerve paresis (P = 0.71), histologic type (P = 0.16), and extent of surgery (P = 0.94). Follow-up for 13 surviving patients ranged from 2.6 to 28.7 (mean, 12.0) years. Neurologic deficits in surviving patients were absent in 15% (two of 13), mild in 62% (eight of 23), and moderate in 23% (three of 13). One case of brain radionecrosis was identified (6000 cGy, 200 cGy daily).

Adolescent↗

A clinicopathologic reappraisal of brain stem tumor classification. Identification of pilocystic astrocytoma and fibrillary astrocytoma as distinct entities.

BACKGROUND: Brain stem tumors in children have been classified pathologically as low grade or high grade gliomas and descriptively as diffuse gliomas, intrinsic gliomas, midbrain tumors, tectal gliomas, pencil gliomas, dorsal exophytic brain stem tumors, pontine gliomas, focal medullary tumors, cervicomedullary tumors, focal gliomas, or cystic gliomas. METHODS: To search for a simplified and prognostic clinicopathologic scheme for brain stem tumors, the authors reviewed a consecutive cohort of patients younger than age 21 years with tumors diagnosed from 1980 through 1997. Pathology specimens and neuroimaging were classified by masked review. Statistical and survival analysis along with Cox proportional hazards regression was performed. RESULTS: Seventy-six patients were identified, with initial diagnostic magnetic resonance imaging available for 51 and pathology specimens for 48 patients. Twenty cases were classified histologically as pilocytic astrocytoma (PA), 14 as fibrillary astrocytoma (FA), and 14 as other tumors or indeterminate pathology. For all tumors, characteristics significantly associated with a worse survival rate were: symptom duration less than 6 months before diagnosis (P = 0.004); abducens palsy at presentation (P < 0.0001); pontine location (P = 0.0002); and engulfment of the basilar artery (P = 0.006). Pilocytic astrocytoma was associated with location outside the ventral pons (P = 0.001) and dorsal exophytic growth (P = 0.013); Fibrillary astrocytoma was associated with symptoms less than 6 months (P = 0. 006), abducens palsy (P < 0.001), and engulfment of the basilar artery (P = 0.002). Pilocytic astrocytoma showed 5-year overall survival (OS) of 95% (standard error [SE], 5%) compared with FA 1-year OS of 23% (SE, 11%;P < 0.0001). CONCLUSIONS: Brain stem tumors can be succinctly and better biologically classified as diffusely infiltrative brain stem gliomas-generally FA located in the ventral pons that present with abducens palsy, often engulf the basilar artery, and carry a grim prognosis-and focal brain stem gliomas-frequently PA arising outside the ventral pons, often with dorsal exophytic growth, a long clinical prodrome, and outstanding prognosis for survival. Our findings emphasize the individuality of PA as a distinct clinicopathologic entity with an exceptional prognosis.

Adolescent↗

Coenzyme Q10, antioxidant status and ApoE isoforms.

The aim of this study was to inquire the antioxidant status in plasma and lipoproteins isolated from normal subjects possessing different ApoE genotypes. For this purpose we investigated blood samples from 106 healthy blood donors: the distribution of ApoE alleles (E2/E2 = 0.9%, E2/E3 = 10.4%, E2/E4 = 2.8%, E3/E3 = 71.7%, E3/E4 = 12.3% and E4/E4 1.9% with 1, 11, 3, 76, 13, and 2 subjects respectively for each genotype) was in agreement with previous data. Almost no differences were found in the concentrations of both coenzyme Q10 (CoQ10) and vitamin E for the different genotypes. Concentration of CoQ10 in isolated lipoproteins was also similar, in the different genotypes, when referred to cholesterol; CoQ10 in LDL was higher for the E3/E3 subjects when referred to protein. Neither CoQ10 nor vitamin E correlated with paraoxonase (PON) activity or cholesteryl-ester hydroperoxides (CHP). Furthermore, there was no correlation between the same lipophilic antioxidants and CHP levels. The only E2 homozygous subject found had high levels of PON and low levels of CHP; the two E4/E4 subjects had low PON activity together with low levels of CHP.

Alleles↗