Total protein and cholesterol concentrations in brain regions of male ...

African Journals Online (AJOL)

The results showed similarities (P>0.05) between the treatments in total protein concentrations in the cerebral cortex, medulla, hypothalamus, amygdala, mesencephalon and hippocampus. Total protein concentrations however differed significantly between diets (P<0.05) in the cerebellum and pons varoli with the lowest ...

Parkinson's disease : The syndrome, the pathogenesis and pathophysiology

NARCIS (Netherlands)

Bartels, Anna L.; Leenders, Klaus L.

Parkinson's disease (PD) is characterised by a slowly expanding degeneration of neurons particularly in the mesencephalon. The causes are unknown although risk factors in the genetic and toxic domain are being discovered. An important pathophysiological feature in PD is the loss of part of the

Cryopreservation of porcine fetal ventral mesencephalic tissue for intrastriatal transplantation in Parkinson's disease

NARCIS (Netherlands)

Koopmans, J.; Hogenesch, I.; Copray, S.; Middel, B.; van Dijk, H.; Go, K-G.; Staal, M.

2001-01-01

In this study we examined the efficacy of cryopreserving porcine fetal mesencephalic tissue. After microscopical dissection of the ventral mesencephalon (VM) from E28 pig fetuses, the collection of explants was randomly divided into two equal parts. One part was directly prepared as cell suspension.

Resting-state brain networks revealed by granger causal connectivity in frogs.

Science.gov (United States)

Xue, Fei; Fang, Guangzhan; Yue, Xizi; Zhao, Ermi; Brauth, Steven E; Tang, Yezhong

2016-10-15

Resting-state networks (RSNs) refer to the spontaneous brain activity generated under resting conditions, which maintain the dynamic connectivity of functional brain networks for automatic perception or higher order cognitive functions. Here, Granger causal connectivity analysis (GCCA) was used to explore brain RSNs in the music frog (Babina daunchina) during different behavioral activity phases. The results reveal that a causal network in the frog brain can be identified during the resting state which reflects both brain lateralization and sexual dimorphism. Specifically (1) ascending causal connections from the left mesencephalon to both sides of the telencephalon are significantly higher than those from the right mesencephalon, while the right telencephalon gives rise to the strongest efferent projections among all brain regions; (2) causal connections from the left mesencephalon in females are significantly higher than those in males and (3) these connections are similar during both the high and low behavioral activity phases in this species although almost all electroencephalograph (EEG) spectral bands showed higher power in the high activity phase for all nodes. The functional features of this network match important characteristics of auditory perception in this species. Thus we propose that this causal network maintains auditory perception during the resting state for unexpected auditory inputs as resting-state networks do in other species. These results are also consistent with the idea that females are more sensitive to auditory stimuli than males during the reproductive season. In addition, these results imply that even when not behaviorally active, the frogs remain vigilant for detecting external stimuli. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Changes caused by haloperidol are blocked by music in Wistar rat.

Science.gov (United States)

Tasset, Inmaculada; Quero, Ismael; García-Mayórgaz, Ángel D; del Río, Manuel Causse; Túnez, Isaac; Montilla, Pedro

2012-06-01

This study sought to evaluate the effect of classical music, using Mozart's sonata for two pianos (K. 448), on changes in dopamine (DA) levels in the striatal nucleus (SN), prefrontal cortex (PFC) and mesencephalon, and on prolactin (PRL) and corticosterone secretion in adult male Wistar rats. Rats were divided into four groups: (1) control, (2) haloperidol treatment (single dose of 2 mg/kg s.c.), (3) music (two 2-h sessions per day) and (4) haloperidol plus music. Rats were sacrificed 2 h after haloperidol injection. Music prompted a fall in plasma PRL and corticosterone levels in healthy rats (P music was associated with a significant increase in DA levels in all groups, with the increase being particularly marked in PFC and SN (P music, by contrast, enhances DA activity and turnover in the brain. The results obtained here bear out reports that music triggers a reduction in systolic pressure and an increase in mesencephalon dopamine levels in human and rats treated with ecstasy, through a calmodulin-dependent system.

Effects of combined BDNF and GDNF treatment on cultured dopaminergic midbrain neurons

DEFF Research Database (Denmark)

Sautter, J; Meyer, Morten; Spenger, C

1998-01-01

Neural transplantation is an experimental therapy for Parkinson's disease. Pretreatment of fetal donor tissue with neurotrophic factors may improve survival of grafted dopaminergic neurons. Free-floating roller tube cultures of fetal rat ventral mesencephalon were treated with brain-derived neuro......Neural transplantation is an experimental therapy for Parkinson's disease. Pretreatment of fetal donor tissue with neurotrophic factors may improve survival of grafted dopaminergic neurons. Free-floating roller tube cultures of fetal rat ventral mesencephalon were treated with brain......-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), or a combination of both. Dopamine content of the culture medium, the number of tyrosine hydroxylase-immunoreactive neurons, and culture volumes were moderately increased in the BDNF- and GDNF-treated cultures but significantly...... increased by 6.8-, 3.2- and 2.4-fold, respectively after treatment with the combination of both factors. We conclude that pretreatment of dopaminergic tissue in culture with a combination of BDNF and GDNF may be an effective means to improve the quality of tissue prior to grafting....

Initial and follow-up MRI in a case of early diagnosed Reye's syndrome

International Nuclear Information System (INIS)

Ozdoba, C.; Pfenninger, J.; Schroth, G.

1997-01-01

Early MRI in a case of clinically established Reye's syndrome confirmed CT findings of compressed ventricles and additionally demonstrated signal alterations in the thalamus, mesencephalon and pons. On follow-up MRI the pontine lesion had vanished by 1 week later, while the thalamic lesion persisted for more than 2 months. The patient, however, recovered without neurological sequelae. (orig.). With 3 figs

Delayed radiation injury of brain stem after radiotherapy in nasopharyngeal carcinoma

International Nuclear Information System (INIS)

Yang Yunli; Liu Yingxin; Xie Dong; Su Danke; Chen Mingzhong

2002-01-01

Objective: To study the clinical characteristics, MRI findings, diagnosis, treatment and prognostic factors of patients with radiation induced brain stem injury in nasopharyngeal carcinoma. Methods: From January 1991 to January 2001, 24 patients with radiation injury of brain stem were treated, 14 males and 10 females. The latency ranged from 6 to 38 months, with a median of 18 months. The lesions were located in the pons in 10 patients, mesencephalon + pons in 4, pons + medulla oblongata in 5, medulla oblongata in 2 and mesencephalon + pons + medulla oblongata in 3. MRI findings showed that the injury was chiefly presented as hypointensity foci on T 1 WI and hyperintensity foci on T 2 WI. Results: Eighteen patients were treated with dexamethasone in the early phase, with symptoms relieved in 12 patients but unimproved in 6 patients. Eight 44% patients died within the 8-38 months, leaving 16 patients surviving for 0.5 to 6.0 years. Conclusions: Radiation injury of brain stem has a short latency with severe symptoms, signifying poor prognosis. It is suggested that adequate reduction of irradiation volume and dose at the brain stem should be able to lower the incidence of brain stem injury

Comparison of gene expression profile in embryonic mesencephalon and neuronal primary cultures.

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Dario Greco

Full Text Available In the mammalian central nervous system (CNS an important contingent of dopaminergic neurons are localized in the substantia nigra and in the ventral tegmental area of the ventral midbrain. They constitute an anatomically and functionally heterogeneous group of cells involved in a variety of regulatory mechanisms, from locomotion to emotional/motivational behavior. Midbrain dopaminergic neuron (mDA primary cultures represent a useful tool to study molecular mechanisms involved in their development and maintenance. Considerable information has been gathered on the mDA neurons development and maturation in vivo, as well as on the molecular features of mDA primary cultures. Here we investigated in detail the gene expression differences between the tissue of origin and ventral midbrain primary cultures enriched in mDA neurons, using microarray technique. We integrated the results based on different re-annotations of the microarray probes. By using knowledge-based gene network techniques and promoter sequence analysis, we also uncovered mechanisms that might regulate the expression of CNS genes involved in the definition of the identity of specific cell types in the ventral midbrain. We integrate bioinformatics and functional genomics, together with developmental neurobiology. Moreover, we propose guidelines for the computational analysis of microarray gene expression data. Our findings help to clarify some molecular aspects of the development and differentiation of DA neurons within the midbrain.

Vitamin D regulates tyrosine hydroxylase expression: N-cadherin a possible mediator.

Science.gov (United States)

Cui, X; Pertile, R; Liu, P; Eyles, D W

2015-09-24

Vitamin D is a neuroactive steroid. Its genomic actions are mediated via the active form of vitamin D, 1,25(OH)2D3, binding to the vitamin D receptor (VDR). The VDR emerges in the rat mesencephalon at embryonic day 12, representing the peak period of dopaminergic cell birth. Our prior studies reveal that developmental vitamin D (DVD)-deficiency alters the ontogeny of dopaminergic neurons in the developing mesencephalon. There is also consistent evidence from others that 1,25(OH)2D3 promotes the survival of dopaminergic neurons in models of dopaminergic toxicity. In both developmental and toxicological studies it has been proposed that 1,25(OH)2D3 may modulate the differentiation and maturation of dopaminergic neurons; however, to date there is lack of direct evidence. The aim of the current study is to investigate this both in vitro using a human SH-SY5Y cell line transfected with rodent VDR and in vivo using a DVD-deficient model. Here we show that in VDR-expressing SH-SY5Y cells, 1,25(OH)2D3 significantly increased production of tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine synthesis. This effect was dose- and time-dependent, but was not due to an increase in TH-positive cell number, nor was it due to the production of trophic survival factors for dopamine neurons such as glial-derived neurotrophic factor (GDNF). In accordance with 1,25(OH)2D3's anti-proliferative actions in the brain, 1,25(OH)2D3 reduced the percentage of dividing cells from approximately 15-10%. Given the recently reported role of N-cadherin in the direct differentiation of dopaminergic neurons, we examined here whether it may be elevated by 1,25(OH)2D3. We confirmed this in vitro and more importantly, we showed DVD-deficiency decreases N-cadherin expression in the embryonic mesencephalon. In summary, in our in vitro model we have shown 1,25(OH)2D3 increases TH expression, decreases proliferation and elevates N-cadherin, a potential factor that mediates these processes

Normal computed tomographic anatomy of the cisterns and cranial nerves

International Nuclear Information System (INIS)

Manelfe, C.; Bonafe, A.

1980-01-01

This study, based on the normal CT anatomy of the cisterns investigated with Metrizamide, aims at attempting to find out with accuracy which plane of section is the most suitable for the investigation of each group of cisterns (posterior fossa, mesencephalon, suprasellar). Moreover we felt it necessary to include our study the normal appearance of the cranial nerves as their normal CT anatymy - optic nerves expected - is not well known yet. (orig./AJ) [de

Molecular and neurochemical substrates of the audiogenic seizure strains: The GASH:Sal model.

Science.gov (United States)

Prieto-Martín, Ana I; Aroca-Aguilar, J Daniel; Sánchez-Sánchez, Francisco; Muñoz, Luis J; López, Dolores E; Escribano, Julio; de Cabo, Carlos

2017-06-01

Animal models of audiogenic epilepsy are useful tools to understand the mechanisms underlying human reflex epilepsies. There is accumulating evidence regarding behavioral, anatomical, electrophysiological, and genetic substrates of audiogenic seizure strains, but there are still aspects concerning their neurochemical basis that remain to be elucidated. Previous studies have shown the involved of γ-amino butyric acid (GABA) in audiogenic seizures. The aim of our research was to clarify the role of the GABAergic system in the generation of epileptic seizures in the genetic audiogenic seizure-prone hamster (GASH:Sal) strain. We studied the K + /Cl - cotransporter KCC2 and β2-GABAA-type receptor (GABAAR) and β3-GABAAR subunit expressions in the GASH:Sal both at rest and after repeated sound-induced seizures in different brain regions using the Western blot technique. We also sequenced the coding region for the KCC2 gene both in wild- type and GASH:Sal hamsters. Lower expression of KCC2 protein was found in GASH:Sal when compared with controls at rest in several brain areas: hippocampus, cortex, cerebellum, hypothalamus, pons-medulla, and mesencephalon. Repeated induction of seizures caused a decrease in KCC2 protein content in the inferior colliculus and hippocampus and an increase in the pons-medulla. When compared to controls, the basal β 2 -GABA A R subunit in the GASH:Sal was overexpressed in the inferior colliculus, rest of the mesencephalon, and cerebellum, whereas basal β 3 subunit levels were lower in the inferior colliculus and rest of the mesencephalon. Repeated seizures increased β2 both in the inferior colliculus and in the hypothalamus and β 3 in the hypothalamus. No differences in the KCC2 gene-coding region were found between GASH:Sal and wild-type hamsters. These data indicate that GABAergic system functioning is impaired in the GASH:Sal strain, and repeated seizures seem to aggravate this dysfunction. These results have potential clinical

Biological and Theoretical Studies of Adaptive Networks: The Conditioned Response.

Science.gov (United States)

1992-06-30

suggest experimental tests and provide direction for physiological studies. 14 SU~la TIPO ~IS- NIJUMS Of PAGIS 17. @1d-ftA ITY CLASSIPtCATICON...mancte suditioned inhibition of the rabbit’s nictitating membrane response, CI tasks require the active suppression of CRs in the Bull . Psychon. Soc., 20... Bull ., 84 (1977) encephalon and mesencephalon26. 690-711. Several lines of evidence suggest that the septal and 8 Evans,J.A.C. and Thornton, E.W

Gadolinium-enhanced MRI in central nervous system Behcet's disease

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Erdem, E. (Dept. of Radiology (Neuroradiology), Hopital de Bicetre, Paris-Sud Univ. (France)); Carlier, R. (Dept. of Radiology (Neuroradiology), Hopital de Bicetre, Paris-Sud Univ. (France)); Idir, A.B.C. (Dept. of Radiology (Neuroradiology), Hopital de Bicetre, Paris-Sud Univ. (France)); Masnou, P.O. (Dept. of Neurology, Hopital de Bicetre, Paris-Sud Univ. (France)); Moulonguet, A. (Dept. of Neurology, Hopital de Bicetre, Paris-Sud Univ. (France)); Adams, D. (Dept. of Neurology, Hopital de Bicetre, Paris-Sud Univ. (France)); Doyon, D. (Dept. of Radiology (Neuroradiology), Hopital de Bicetre, Paris-Sud Univ. (France))

1993-02-01

Two cases of central nervous system Behcet's disease, studied by gadolinium-enhanced MRI, are presented. In one patient, whose clinical picture was dominated by a brain stem syndrome, the gadolinium enhancement resolved with clinical improvement, although the hyperintense areas in the mesencephalon on T2-weighted images persisted. In the second, who had a pseudobulbar palsy and a mild right hemiparesis, there were many abnormal areas, but an enhancing focus in the posterior limb of the left internal capsule was probably the lesion responsible for the hemiparesis. (orig.)

Nitration of soluble proteins in organotypic culture models of Parkinson's disease

DEFF Research Database (Denmark)

Larsen, Trine R; Söderling, Ann-Sofi; Caidahl, Kenneth

2008-01-01

Protein nitration due to oxidative and nitrative stress has been linked to the pathogenesis of Parkinson's disease (PD), but its relationship to the loss of dopamine (DA) or tyrosine hydroxylase (TH) activity is not clear. Here we quantified protein-bound 3-nitrotyrosine (3-NT) by a novel gas...... chromatography/negative chemical ionization tandem mass spectrometry technique and DA and 3,4-dihydroxyphenylalanine (DOPA) by HPLC in tissues or medium of organotypic, mouse mesencephalon cultures after acute or chronic treatments with the peroxynitrite donor 3-morpholino-sydnonimine (SIN-1), the dopaminergic...

Hyperintense basal ganglia lesions on T1-weighted MR images in asymptomatic patients with hepatic dysfunction

Energy Technology Data Exchange (ETDEWEB)

Saatci, I. [Dept. of Radiology, Hacettepe Univ. Hospital, Ankara (Turkey); Cila, A. [Dept. of Radiology, Hacettepe Univ. Hospital, Ankara (Turkey); Dincer, F.F. [Dept. of Radiology, Hacettepe Univ. Hospital, Ankara (Turkey)

1995-12-31

Cranial MRI findings in four patients who had hepatic dysfunction, including one with sole hepatic form of Wilson`s disease, were reported. The MR examinations revealed bilateral, symmetric hyperintensity in the globus pallidus, subthalamic nuclei and mesencephalon on T1-weighted images with no corresponding abnormality on T2-weighted sequences. The basal ganglia were normal on CT examinations in all patients. None of the patients had the clinical findings of hepatic encephalopathy. The MR findings in our patients did not correlate with the degree or duration of hepatic dysfunction. (orig.)

Kinetics of 137cesium in cerebral structures and blood

International Nuclear Information System (INIS)

Ribas, B.; Gonzalez, M.D.; Rio, J. del; Reus, M.I.S.; Gonzalez-Baron, M.

1987-01-01

The old clinical use of cesium in epilepsy expresses a relation of this metal with the central nervous system. Two groups of male Wistar rats of 200 g were administered single doses of 50μCi intravenously for blood kinetics and 2μCi 137 CsCl in each lateral ventricle of the brain for the kinetics in the cerebral structures, respectively. In both cases under ether anesthesia. Blood samples of IV gouts were weighed, and cerebral structure hypothalamus, hypocampus, striatum, cortex, cerebellum, mesencephalon and medulla oblongata dissected, cleaned, washed, dried, weighed, and in both cases cpm of the samples evaluated submitting it to the gamma radiations detector. In both experimental values of the 137 CsCl kinetics are expressed and applying the retroprojection method; parameters and constants are obtained. tsub(1/2) alpha = 0.0358 h and tsub(1/2) beta = 6.7159 h. In tables the equations of the alpha and beta phases are expressed. In blood after the rapid diminution of the radioactivity in the first 5 min the equilibrium phase is reached in 30 min afterwards, and the values remain almost the same 4 h after the injection and cesium is slowly eliminated by the rat. Cerebral structures after its intracerebroventricular application show that cesium has a great uptake velocity, it is rapidly incorporated by hypothalamus and after by cortex, hypocampus, striatum, mesencephalon and medulla oblongata, the two last showing the slower incorporation. After 24 h the cesium radioactivity declines slowly and progressively. (author)

Effect of radiation and serotonin treatment on serotoninergic system of mouse fetal mesencephalon and diencophalon

International Nuclear Information System (INIS)

Sapronova, A.Ya.; Proshlyakova, E.V.; Konstantinova, M.M.; Panaeva, S.V.; Podmareva, O.N.; Voronova, S.N.; Ugryumov, M.V.; Turpaev, T.M.

1996-01-01

Effect of radiation and introduction of serotonin before and after irradiation in the critical period of nervous system development on functional state of serotoninergic system of the mice marrow by the moment of their birth was determined. The revealed radioprotective effect of serotonin and its therapeutic effect after irradiation show that these effects are not conditioned by changes in the functional state of the serotoninergic system of the average and intermediate marrow of the mice fetus

Atlas of neuroanatomy with radiologic correlation and pathologic illustration

International Nuclear Information System (INIS)

Dublin, A.B.; Dublin, W.B.

1982-01-01

This atlas correlates gross neuroanatomic specimens with radiographs and computed tomographic scans. Pathologic specimens and radiographs are displayed in a similar manner. The first chapter, on embryology, shows the development of the telencephalon, diencephalon, mesencephalon, and metencephalon through a series of overlays. The anatomical section shows the surface of the brain, the ventricles and their adjacent structures, and the vascular system. CT anatomy is demonstrated by correlating CT scans with pathologic brain specimens cut in the axial plane. Pathologic changes associated with congenital malformations, injections, injuries, tumors, and other causes are demonstrated in the last six chapters

Reversibility of ecstasy-induced reduction in serotonin transporter availability in polydrug ecstasy users

International Nuclear Information System (INIS)

Buchert, Ralph; Wilke, Florian; Nebeling, Bruno; Clausen, Malte; Thomasius, Rainer; Petersen, Kay; Obrocki, Jost; Wartberg, Lutz; Zapletalova, Pavlina

2006-01-01

Animal data suggest that the synthetic drug ecstasy may damage brain serotonin neurons. Previously we reported protracted reductions in the availability of the serotonin transporter (SERT), an index of integrity of the axon terminals of brain serotonergic neurons, in SERT-rich brain regions in current human ecstasy users. Comparison of current ecstasy users and former ecstasy users yielded some evidence that this reduction might be reversible. However, participant selection effects could not be ruled out. Therefore, follow-up examinations were performed in these subjects to test the following a priori hypothesis in a prospective longitudinal design that eliminates participant selection effects to a large extent: availability of the SERT increases towards normal levels when ecstasy use is stopped, and remains unchanged or is further decreased if use is continued. Two follow-up positron emission tomography measurements using the SERT ligand [ 11 C](+)McN5652 were completed by 15 current and nine former ecstasy users. All subjects used illicit drugs other than ecstasy, too. The time interval between repeated measurements was about 1 year. The time course of the availability of the SERT was analysed in the following SERT-rich regions: mesencephalon, putamen, caudate and thalamus. Current ecstasy users showed a consistent increase in the availability of the SERT in the mesencephalon during the study (Friedman test: p=0.010), which most likely was caused by a decrease in the intensity of ecstasy consumption (Spearman correlation coefficient -0.725, p=0.002). Former ecstasy users showed a consistent increase in SERT availability in the thalamus (Friedman test: p=0.006). Ecstasy-induced protracted alterations in the availability of the SERT might be reversible. (orig.)

Reversibility of ecstasy-induced reduction in serotonin transporter availability in polydrug ecstasy users

Energy Technology Data Exchange (ETDEWEB)

Buchert, Ralph; Wilke, Florian; Nebeling, Bruno; Clausen, Malte [University Medical Center Hamburg-Eppendorf, Department of Nuclear Medicine, Hamburg (Germany); Thomasius, Rainer; Petersen, Kay; Obrocki, Jost; Wartberg, Lutz; Zapletalova, Pavlina [University Medical Center Hamburg-Eppendorf, Departments of Psychiatry and Psychotherapy, Hamburg (Germany)

2006-02-01

Animal data suggest that the synthetic drug ecstasy may damage brain serotonin neurons. Previously we reported protracted reductions in the availability of the serotonin transporter (SERT), an index of integrity of the axon terminals of brain serotonergic neurons, in SERT-rich brain regions in current human ecstasy users. Comparison of current ecstasy users and former ecstasy users yielded some evidence that this reduction might be reversible. However, participant selection effects could not be ruled out. Therefore, follow-up examinations were performed in these subjects to test the following a priori hypothesis in a prospective longitudinal design that eliminates participant selection effects to a large extent: availability of the SERT increases towards normal levels when ecstasy use is stopped, and remains unchanged or is further decreased if use is continued. Two follow-up positron emission tomography measurements using the SERT ligand [{sup 11}C](+)McN5652 were completed by 15 current and nine former ecstasy users. All subjects used illicit drugs other than ecstasy, too. The time interval between repeated measurements was about 1 year. The time course of the availability of the SERT was analysed in the following SERT-rich regions: mesencephalon, putamen, caudate and thalamus. Current ecstasy users showed a consistent increase in the availability of the SERT in the mesencephalon during the study (Friedman test: p=0.010), which most likely was caused by a decrease in the intensity of ecstasy consumption (Spearman correlation coefficient -0.725, p=0.002). Former ecstasy users showed a consistent increase in SERT availability in the thalamus (Friedman test: p=0.006). Ecstasy-induced protracted alterations in the availability of the SERT might be reversible. (orig.)

Synapsin I (Protein I) in different brain regions in senile dementia of Alzheimer type and in multiinfarct dementia. [Radioimmunoassay

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Adolfsson, R; Alafuzoff, I; Winblad, B [Umeaa Univ. (Sweden); Perdahl, E; Albert, K A; Nestler, E J; Greengard, P [Rockefeller Univ., New York (USA)

1984-01-01

Synapsin I (Protein I), a neuron-specfic phosphoprotein enriched in presynaptic nerve terminals, has been used as a quantitative marker for the density of nerve terminals in five brain regions (caudate nucleus, cingulate gyrus, hippocampus, mesencephalon and putamen) from patients who had suffered from Alzheimer disease/senile dementia of Alzheimer type (AD/SDAT), from patients with multi-infarct dementia (MID), and from agematched controls. Samples were obtained at autopsy. Lower levels of Synapsin I were observed in the hippocampus of patients with AD/SDAT but not with MID. There were no significant differences in Synapsin I levels between patients and controls in any of the other four brain regions examined.

Synapsin I (protein I) in different brain regions in senile dementia of Alzheimer type and in multiinfarct dementia

International Nuclear Information System (INIS)

Adolfsson, R.; Alafuzoff, I.; Winblad, B.; Perdahl, E.; Albert, K.A.; Nestler, E.J.; Greengard, P.

1984-01-01

Synapsin I (Protein I), a neuron-specfic phosphoprotein enriched in presynaptic nerve terminals, has been used as a quantitative marker for the density of nerve terminals in five brain regions (caudate nucleus, cingulate gyrus, hippocampus, mesencephalon and putamen) from patients who had suffered from Alzheimer disease/senile dementia of Alzheimer type (AD/SDAT), from patients with multi-infarct dementia (MID), and from agematched controls. Samples were obtained at autopsy. Lower levels of Synapsin I were observed in the hippocampus of patients with AD/SDAT but not with MID. There were no significant differences in Synapsin I levels between patients and controls in any of the other four brain regions examined. (Author)

Expansion and characterization of ventral mesencephalic precursor cells: effect of mitogens and investigation of FA1 as a potential dopaminergic marker

DEFF Research Database (Denmark)

Jensen, Pia; Bauer, Matthias; Jensen, Charlotte H

2007-01-01

factor 8 (FGF8) for expansion of such dopaminergic precursor cells, and fetal antigen-1 (FA1), a secreted neuronal protein of unknown function, as a non-invasive dopaminergic marker. Tissue from embryonic day (ED) 12 rat ventral mesencephalon was dissociated mechanically and cultured for 4 days...... to controls. After differentiation, biochemical analyses showed significantly more dopamine and FA1 in conditioned medium from both FGF2 and FGF8 expanded cultures than in controls. Correspondingly, numbers of tyrosine hydroxylase (TH)- and FA1-immunoreactive cells had increased 16-fold (P ... for these cells. Furthermore, FA1 was identified as a potential supplementary non-invasive marker of cultured dopaminergic neurons....

Isovaleric acidaemia: cranial CT and MRI findings

International Nuclear Information System (INIS)

Sogut, Ayhan; Acun, Ceyda; Tomsac, Nazan; Demirel, Fatma; Aydin, Kubilay; Aktuglu, Cigdem

2004-01-01

Isovaleric acidaemia is an inborn error of leucine metabolism due to deficiency of isovaleryl-CoA dehydrogenase, which results in accumulation of isovaleric acid in body fluids. There are acute and chronic-intermittent forms of the disease. We present the cranial CT and MRI findings of a 19-month-old girl with the chronic-intermittent form of isovaleric acidaemia. She presented with severe metabolic acidosis, hyperglycaemia, glycosuria, ketonuria and acute encephalopathy. Cranial CT revealed bilateral hypodensity of the globi pallidi. MRI showed signal changes in the globi pallidi and corticospinal tracts of the mesencephalon, which were hypointense on T1-weighted and hyperintense on T2-weighted images. (orig.)

Isovaleric acidaemia: cranial CT and MRI findings

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Sogut, Ayhan; Acun, Ceyda; Tomsac, Nazan; Demirel, Fatma [Department of Paediatrics, Karaelmas University, Zonguldak (Turkey); Aydin, Kubilay [Department of Radiology, Istanbul Medical School, Istanbul University, Camlikyolu, B. mehmetpasa sokak yavuz apt. No:10/10, Etiler, Istanbul (Turkey); Aktuglu, Cigdem [Department of Paediatrics, Cerrahpasa Medical School, Istanbul University, Istanbul (Turkey)

2004-02-01

Isovaleric acidaemia is an inborn error of leucine metabolism due to deficiency of isovaleryl-CoA dehydrogenase, which results in accumulation of isovaleric acid in body fluids. There are acute and chronic-intermittent forms of the disease. We present the cranial CT and MRI findings of a 19-month-old girl with the chronic-intermittent form of isovaleric acidaemia. She presented with severe metabolic acidosis, hyperglycaemia, glycosuria, ketonuria and acute encephalopathy. Cranial CT revealed bilateral hypodensity of the globi pallidi. MRI showed signal changes in the globi pallidi and corticospinal tracts of the mesencephalon, which were hypointense on T1-weighted and hyperintense on T2-weighted images. (orig.)

Diffuse and focal presentations of brainstem tumors in children: the images and the prognostic value; Presentacion difusa o focal de los tumores troncoencefalicos en los ninos: imagen y valor pronostico

Energy Technology Data Exchange (ETDEWEB)

Menor, F.; Canete, A.; Romero, M. J.; Trilles, L.; Carvajal, E. [Hospital Universitario La Fe. Valencia (Spain); Marti-Bonmati, L. [Hospital Universitario Dr. Peset. Valencia (Spain)

2000-07-01

To determine whether the presentation of brainstem tumors as diffuse or focal lesions showed any prognostic value in children. A retrospective review was carried out of the neuroradiological findings in 43 children with brainstem tumors, all of whom underwent computed tomography (CT) and 31 of whom underwent magnetic resonance (MR). The diffuse tumors (n=20) were all located in the pons, spreading to mesencephalon in 6 cases and to medulla oblongata in 1, and exhibiting exophytic growth, preferentially to the prepontine cistern. They presented homogeneous low attenuation in CT (90%) and decrease/increased signal intensity in T1/T2-weighted MR images (91.6%). Contrast uptake was observed in 20% of cases, with agreement between CT and MR. The patients showed a good initial response to treatment (70%), a high rate of relapse (80%) and a 5-year survival of 12%. The focal tumors were located in the pons (11 cases, spreading to the medulla oblongata in 2), mesencephalon (11 cases, 9 tectal and 2 peduncular) and medulla oblongata (1 case), and exhibited exophytic growth predominantly to the pontocerebellar junction and to the cerebellar peduncles. They showed a certain tendency toward heterogeneity (21.7%), toward isoattenuation in CT (47.8%) and isointensity in T1-weighted MR images (26.3%). CT showed a rate of tumor uptake of 26%, while the rate of contrast iptake was 58% MR. Fifty percent of these lesions responded well to therapy, with a recurrence rate of 28% and 4-year survival of 63%. Neuroimaging helps to define two basic patterns in brainstem tumors that play a role in prognosis. The diffuse tumor, which characteristically shows a good initial response to therapy, has a worse prognosis, probably reflecting its histological aggressiveness. (Author) 21 refs.

Diffuse and focal presentations of brainstem tumors in children: the images and the prognostic value

International Nuclear Information System (INIS)

Menor, F.; Canete, A.; Romero, M. J.; Trilles, L.; Carvajal, E.; Marti-Bonmati, L.

2000-01-01

To determine whether the presentation of brainstem tumors as diffuse or focal lesions showed any prognostic value in children. A retrospective review was carried out of the neuroradiological findings in 43 children with brainstem tumors, all of whom underwent computed tomography (CT) and 31 of whom underwent magnetic resonance (MR). The diffuse tumors (n=20) were all located in the pons, spreading to mesencephalon in 6 cases and to medulla oblongata in 1, and exhibiting exophytic growth, preferentially to the prepontine cistern. They presented homogeneous low attenuation in CT (90%) and decrease/increased signal intensity in T1/T2-weighted MR images (91.6%). Contrast uptake was observed in 20% of cases, with agreement between CT and MR. The patients showed a good initial response to treatment (70%), a high rate of relapse (80%) and a 5-year survival of 12%. The focal tumors were located in the pons (11 cases, spreading to the medulla oblongata in 2), mesencephalon (11 cases, 9 tectal and 2 peduncular) and medulla oblongata (1 case), and exhibited exophytic growth predominantly to the pontocerebellar junction and to the cerebellar peduncles. They showed a certain tendency toward heterogeneity (21.7%), toward isoattenuation in CT (47.8%) and isointensity in T1-weighted MR images (26.3%). CT showed a rate of tumor uptake of 26%, while the rate of contrast iptake was 58% MR. Fifty percent of these lesions responded well to therapy, with a recurrence rate of 28% and 4-year survival of 63%. Neuroimaging helps to define two basic patterns in brainstem tumors that play a role in prognosis. The diffuse tumor, which characteristically shows a good initial response to therapy, has a worse prognosis, probably reflecting its histological aggressiveness. (Author) 21 refs

Combined Ipsilateral Oculomotor Nerve Palsy and Contralateral Downbeat Nystagmus in a Case of Cerebral Infarction

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Kosuke Matsuzono

2014-04-01

Full Text Available We report a patient with acute cerebral infarction of the left paramedian thalamus, upper mesencephalon and cerebellum who exhibited ipsilateral oculomotor nerve palsy and contralateral downbeat nystagmus. The site of the infarction was considered to be the paramedian thalamopeduncular and cerebellar regions, which are supplied by the superior cerebellar artery containing direct perforating branches or both the superior cerebellar artery and the superior mesencephalic and posterior thalamosubthalamic arteries. Contralateral and monocular downbeat nystagmus is very rare. Our case suggests that the present downbeat nystagmus was due to dysfunction of cerebellar-modulated crossed oculovestibular fibers of the superior cerebellar peduncle or bilateral downbeat nystagmus with one-sided oculomotor nerve palsy.

Estrogen receptor-alpha-immunoreactive neurons in the mesencephalon, pons and medulla oblongata of the female golden hamster

NARCIS (Netherlands)

Boers, J; Gerrits, PO; Holstege, G

1999-01-01

Recent studies have revealed brainstem-spinal pathways involved in the generation of receptive behavior in hamster and cat, and the enormous influence of estrogen on these pathways. The present study gives an overview of the location of estrogen receptor-alpha-immunoreactive neurons (ER-alpha-IR) in

Hydrocephalus caused by conditional ablation of the Pten or beta-catenin gene

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Ohtoshi Akihira

2008-10-01

Full Text Available Abstract To investigate the roles of Pten and β-Catenin in the midbrain, either the Pten gene or the β-catenin gene was conditionally ablated, using Dmbx1 (diencephalon/mesencephalon-expressed brain homeobox gene 1-Cre mice. Homozygous disruption of the Pten or β-catenin gene in Dmbx1-expressing cells caused severe hydrocephalus and mortality during the postnatal period. Conditional deletion of Pten resulted in enlargement of midbrain structures. β-catenin conditional mutant mice showed malformation of the superior and inferior colliculi and stenosis of the midbrain aqueduct. These results demonstrate that both Pten and β-Catenin are essential for proper midbrain development, and provide the direct evidence that mutations of both Pten and β-catenin lead to hydrocephalus.

Generation and properties of a new human ventral mesencephalic neural stem cell line

DEFF Research Database (Denmark)

Villa, Ana; Liste, Isabel; Courtois, Elise T

2009-01-01

. Here we report the generation of a new stable cell line of human neural stem cells derived from ventral mesencephalon (hVM1) based on v-myc immortalization. The cells expressed neural stem cell and radial glia markers like nestin, vimentin and 3CB2 under proliferation conditions. After withdrawal......Neural stem cells (NSCs) are powerful research tools for the design and discovery of new approaches to cell therapy in neurodegenerative diseases like Parkinson's disease. Several epigenetic and genetic strategies have been tested for long-term maintenance and expansion of these cells in vitro...... derivatives may constitute good candidates for the study of development and physiology of human dopaminergic neurons in vitro, and to develop tools for Parkinson's disease cell replacement preclinical research and drug testing....

Dopamine release in organotypic cultures of foetal mouse mesencephalon: effects of depolarizing agents, pargyline, nomifensine, tetrodotoxin and calcium

DEFF Research Database (Denmark)

Larsen, Trine R; Rossen, Sine; Gramsbergen, Jan B

2008-01-01

Organotypic mesencephalic cultures provide an attractive in vitro alternative to study development of the nigrostriatal system and pathophysiological mechanisms related to Parkinson's disease. However, dopamine (DA) release mechanisms have been poorly characterized in such cultures. We report her...

Axonal transport and incorporation of radioactivity after injection of N-[3H]acetyl-D-mannosamine into rat mesencephalon

International Nuclear Information System (INIS)

Loopuijt, L.D.

1980-01-01

A study has been performed to demonstrate the possibility of incorporation of sialic acid into nerve endings of the rubrospinal tract after antegrade axonal transport. Young adult rats received injections of N-[ 3 H]acetyl-D-mannosamine into the red nucleus and axonal transport of the tritiated compounds along the axons of afferent and efferent connections of the red nucleus was studied and the transported material was analysed. Light microscopic autoradiography and biochemical methods were used. (Auth./C.F.)

Development of striatal patch/matrix organization in organotypic co-cultures of perinatal striatum, cortex and substantia nigra.

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Snyder-Keller, A; Costantini, L C; Graber, D J

2001-01-01

Organotypic cultures of fetal or early postnatal striatum were used to assess striatal patch formation and maintenance in the presence or absence of dopaminergic and glutamatergic influences. Vibratome-cut slices of the striatum prepared from embryonic day 19 to postnatal day 4 rat pups were maintained in static culture on clear membrane inserts in Dulbecco's modified Eagle's medium/F12 (1:1) with 20% horse serum. Some were co-cultured with embryonic day 12-16 ventral mesencephalon and/or embryonic day 19 to postnatal day 4 cortex, which produced a dense dopaminergic innervation and a modest cortical innervation. Donors of striatal and cortical tissue were previously injected with bromo-deoxyuridine (BrdU) on embryonic days 13 and 14 in order to label striatal neurons destined to populate the patch compartment of the striatum. Patches of BrdU-immunoreactive cells were maintained in organotypic cultures of late prenatal (embryonic days 20-22) or early postnatal striatum in the absence of nigral dopaminergic or cortical glutamatergic influences. In slices taken from embryonic day 19 fetuses prior to the time of in vivo patch formation, patches were observed to form after 10 days in vitro, in 39% of nigral-striatal co-cultures compared to 6% of striatal slices cultured alone or in the presence of cortex only. Patches of dopaminergic fibers, revealed by tyrosine hydroxylase immunoreactivity, were observed in the majority of nigral-striatal co-cultures. Immunostaining for the AMPA-type glutamate receptor GluR1 revealed a dense patch distribution in nearly all cultures, which developed in embryonic day 19 cultures after at least six days in vitro. These findings indicate that striatal patch/matrix organization is maintained in organotypic culture, and can be induced to form in vitro in striatal slices removed from fetuses prior to the time of in vivo patch formation. Furthermore, dopaminergic innervation from co-cultured pieces of ventral mesencephalon enhances patch

CT Scan Features of Presumptive Haemorrhagic Stroke in a Dog with Cushing’s Disease

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A. Liotta

2014-01-01

Full Text Available A 9-year-old, intact male, Brie’s shepherd dog, with a 10-day history of depression and tachypnoea developed signs of central neurological dysfunction. 16 Multislice Computed Tomography (CT pre- and postcontrast studies of the brain revealed a single intra-axial homogeneous well-circumscribed hyperattenuating (+/− 62 HU and noncontrast-enhancing area, 5 mm in diameter, in the caudal part of the mesencephalon. This finding was highly suggestive of a haemorrhagic event. A pituitary-dependent hyperadrenocorticism (PDH was identified and is considered likely to be the underlying cause. A repeat CT scan examination, 2 months later, showed almost complete resolution of the brain lesion. The present case describes a solitary 5 mm diameter lesion: the result of intracranial haemorrhage in a dog with presumed PDH.

A subpopulation of dopaminergic neurons co-expresses serotonin in ventral mesencephalic cultures but not after intrastriatal transplantation in a rat model of Parkinsons disease

DEFF Research Database (Denmark)

Di Santo, Stefano; Seiler, Stefanie; Ducray, Angélique

2017-01-01

Cell replacement therapy is a promising avenue into the investigation and treatment of Parkinson’s disease (PD) and in some cases significant long-term motor improvements have been demonstrated. The main source of donor tissue is the human fetal ventral mesencephalon (VM), which consists...... 30% of the dopaminergic neurons in the donor tissue co-expressed serotonin, no co-localization could be detected in grafts one month after intrastriatal transplantation into hemi-parkinsonian rats. In conclusion, a significant and susceptible sub-population of dopaminergic neurons in fetal VM tissues...... both fetal rat and human dissociated, organotypic and neurosphere VM cultures as well as an animal model of PD were investigated. In dissociated rat VM cultures approximately 30% of the TH positive neurons co-expressed serotonin, while no co-localization with GABA was observed. Interestingly, co...

[Locked-in syndrome. Report of a case and review of the literature].

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Farage Filho, M; Gomes, M D

1982-09-01

The case of a 46 year-old man who had a locked-in syndrome is reported. The patient had a haemorragic vascular accident with tetraplegia, anartria, vertical ocular movements and preservation of the consciousness. The EEG showed a projected disturbance possibly caused by a brain-stem lesion, that was confirmed by the CAT SCAN. Cerebral angiography showed high level of aterosclerosis. The lesion is located in the ventral part of the pons above the nucleus of the abducent nerve, without damaging the substantia reticularis of the mesencephalon and can be caused by thrombosis of the basilar artery and tumor, myastenia gravis, polyneurites, heroin overdose, after swine-flu inoculation and post-infectious polyneurites. The patient is still alive 2 years after the stroke with a good recovery. He can walk and speak fluently, but with cordonal ataxy of the limbs.

Giant posterior fossa mature teratoma with adjacent subacute haematoma, compressive on the brainstem, with acute hydrocephalus. Case report

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Balasa D.

2016-09-01

Full Text Available Mature teratoma of the vermis is a rare entity in neurosurgical adulthood pathology. We present the case of a 65 years old patient, admited as an emergency for intense headache (VAS 8/10, nausea, vomiting, gait ataxia, orizontal nistagmus, dismetria, disdiadocokinezia, predominant on the left side, long tracts signs, predominant on the left side. Native and contrast CT and MRI scan of the head revealed a tumoral lesion, in the vermian, paravermian and in the fourth ventricle, with the aspect of a teratoma with intratumoral subacute haemorrhage including a giant lesion 5,5/5/4,5 cm, compressive on mesencephalon, and with suprajacent acute internal hidrocephalus. Emergency neurosurgery was performed (occipital infratentorial craniectomy, microneurosurgical total tumoral resection and haematoma evacuation. Postoperative, the patient recovered progressivelly , subtotal neo and arhicerebellar symptoms. The motor long tract signs recovered slower and persisted incomplete.

Comparison of mesencephalic free-floating tissue culture grafts and cell suspension grafts in the 6-hydroxydopamine-lesioned rat

DEFF Research Database (Denmark)

Meyer, Morten; Widmer, H R; Wagner, B

1998-01-01

of grafted dopaminergic neurons and to correlate that with the behavioral effects. Additional cultures and acutely prepared explants were also fixed and stored for histological investigation in order to estimate the loss of dopaminergic neurons in culture and after transplantation. Similar behavioral...... numbers of TH-immunoreactive (TH-ir) neurons in grafts of cultured tissue (775 +/- 98, mean +/- SEM) and grafts of fresh, dissociated cell suspension (806 +/- 105, mean +/- SEM). Cell counts in fresh explants, 7-day-old cultures, and grafted cultures revealed a 68.2% loss of TH-ir cells 7 days after......Ventral mesencephalon (VM) of fetal rat and human origin grown as free-floating roller-tube (FFRT) cultures can survive subsequent grafting to the adult rat striatum. To further explore the functional efficacy of such grafts, embryonic day 13 ventral mesencephalic tissue was grafted either after 7...

Divergence of brain and retinal anatomy and histology in pelagic antarctic notothenioid fishes of the sister taxa Dissostichus and Pleuragramma.

Science.gov (United States)

Eastman, Joseph T; Lannoo, Michael J

2011-04-01

The neutrally buoyant Antarctic fishes of the sister taxa Dissostichus (D. eleginoides and D. mawsoni) and Pleuragramma antarcticum diverged early in the notothenioid radiation and filled different niches in the pelagic realm of the developing Southern Ocean. To assess the influence of phylogenetic and ecological factors in shaping neural morphology in these taxa, we studied the anatomy and histology of the brains and retinae, and determined the proportional weights of brain regions. With the brain of the non-Antarctic sister taxon Eleginops maclovinus as plesiomorphic, statistically significant departures in the brains of the two Antarctic taxa include reduction of the corpus cerebelli and expansion of the mesencephalon and medulla. Compared to Eleginops, both species also have a relatively smaller telencephalon, although this is significant only in Dissostichus. There are a number of apomorphic features in the brain of Pleuragramma including reduced olfactory nerves and bulbs, an extremely small corpus cerebelli and an expanded mesencephalon. Although there is not a significant difference in the relative weights of the medulla in the two taxa, the prominence of the eminentia granularis and bulging cap-like appearance of the crista cerebellaris are distinctive in Pleuragramma. Brain histology of Dissostichus and Pleuragramma reflects typical perciform patterns and the two species of Dissostichus are histologically identical. Lateral compression in Pleuragramma and notable lobation in Dissostichus also contribute to differences between the taxa. Compression in Pleuragramma is attributable to convergence on an anchovy/herring body shape and to the relatively large brain in this small fish. The less prominent pattern of lobation of the telencephalon, inferior lobes and corpus cerebelli in Pleuragramma probably reflects underlying histology, specifically a reduction in cellularity of the neuropil in the nuclei and lobes. The retinal histology of Dissostichus and

Nitric oxide is a mediator of methamphetamine (METH)-induced neurotoxicity. In vitro evidence from primary cultures of mesencephalic cells.

Science.gov (United States)

Sheng, P; Cerruti, C; Ali, S; Cadet, J L

1996-10-31

METH is a monoaminergic toxic that destroys dopamine terminals in vivo. Oxidative mechanisms associated with DA metabolism are thought to play an important role in its toxic effects. These ideas were supported by the demonstration that CuZn-superoxide dismutase (CuZnSOD) transgenic mice were protected against the toxic effects of the drug. In the present study, we sought to determine if nitric oxide (NO) production was also involved in METH-induced neurotoxicity using primary cultures obtained from fetal rat mesencephalon. METH caused dose- and time-dependent cell death in vitro. Blockade of nitric oxide (NO) formation with several nitric oxide (NO) synthase blockers attenuated METH-mediated toxicity. Moreover, inhibition of ADP-ribosylation with nicotinamide and benzamide also provided protection against the toxicity of the drug. These results, together with our previous results in transgenic mice, support a role for free radicals in METH-induced toxic effects.

Regional distribution of TL-201 in the brain and spinal cord after injection into the cerebrospinal fluid: Imaging of brain tumors

International Nuclear Information System (INIS)

Woo, D.V.; Rubertone, J.; Vincent, S.; Brady, L.W. Jr.

1986-01-01

Radiotracers are typically employed to evaluate the brain ventricular space; however, there are no agents designed to be taken up into specific neuronal regions after injection into the cerebrospinal fluids (CSF). The authors report studies in which T1-201 was stereotaxically administered into the lateral or fourth ventricles of Sprague-Dawley rats. Brains were removed (n = 42) 2-6 hours after injection and sectioned for apposition to autoradiographic film. Specific uptake was observed in active neurons of the diencephalon, mesencephalon, cerebellum, brain stem, and spinal gray matter. Astrocytoma cell implants into the caudate nucleus of Sprague-Dawley rats induced histologically confirmed brain tumors (n = 5). Significant localization of T1-201 was observed in the tumor 4 hours after injection into the lateral ventricle. These findings suggest that T1-201 may be useful for delineating specific neuronal function via CSF circulation and for imaging actively growing brain tumors

Anatomic and pathologic features of third cranial nerve disorders according to magnetic resonance studies

International Nuclear Information System (INIS)

Ruiz, Y.; Torres, J.; Ramos, M.; Caniego, J.L.; Manzanares, R.; Fresno, L.F.

1998-01-01

The objective of this report is to demonstrate the utility of magnetic resonance (MR) in the diagnosis of disorders involving the third cranial nerves. We have selected MR studies corresponding to patients with an anomaly affecting the third cranial nerves, whether alone or in combination with other cranial nerves. In order to better study the pathology of these cranial nerves, we considered four different segments of the nerves: mesencephalic, cisternal, cavernous and orbital. We present the MR features of the anatomy of the third cranial nerves and the most representative lesions affecting the different intracranial segments: infraction, multiple sclerosis, glioma and cavernoma in the mesencephalon; posterior communicating artery aneurysm, neuritis, neurinomas and meningioma in the cisternal segment; aneurysm of the internal carotid artery, cavernous carotid fistula, metastasis and meningioma in the cavernous sinus and Tolosa-Hunt syndrome in the orbital apex. (Author) 11 refs

The Pathology of Wobbly Hedgehog Syndrome.

Science.gov (United States)

Díaz-Delgado, Josué; Whitley, Derick B; Storts, Ralph W; Heatley, Jill J; Hoppes, Sharman; Porter, Brian F

2018-01-01

Wobbly hedgehog syndrome (WHS) is a leading cause of neurologic disease in African pygmy hedgehogs (APHs; Atelerix albiventris). This study describes the signalment, clinical signs, gross, microscopic, and ultrastructural lesions of WHS in a cohort of 12 pet APHs. Microscopically, lesions consisted of status spongiosus of the white matter, typically bilateral and symmetrical, with myelin degeneration and loss that was accompanied by neuronal/axonal degeneration plus reactive microgliosis and mild, focal astrocytosis and astrogliosis. Lesions were most severe in the cerebellum and medulla oblongata, as well as cervical and thoracic spinal cord. Less affected areas were the corona radiata, corpus callosum, corpus striatum, internal capsule, and the mesencephalon. Ultrastructurally, the lesions consisted of splitting of the myelin sheath at the intraperiod line with subsequent focal expansion, resulting in status spongiosus, disruption, dilatation, rhexis, and phagocytosis. Based on these results, WHS is best described as a "spongy myelinopathy" with widespread central nervous system involvement.

Spatio-temporal neural stem cell behavior that leads to both perfect and imperfect structural brain regeneration in adult newts.

Science.gov (United States)

Urata, Yuko; Yamashita, Wataru; Inoue, Takeshi; Agata, Kiyokazu

2018-06-14

Adult newts can regenerate large parts of their brain from adult neural stem cells (NSCs), but how adult NSCs reorganize brain structures during regeneration remains unclear. In development, elaborate brain structures are produced under broadly coordinated regulations of embryonic NSCs in the neural tube, whereas brain regeneration entails exquisite control of the reestablishment of certain brain parts, suggesting a yet-unknown mechanism directs NSCs upon partial brain excision. Here we report that upon one-quarter excision of the adult newt ( Pleurodeles waltl ) mesencephalon, active participation of local NSCs around specific brain subregions' boundaries leads to some imperfect and some perfect brain regeneration along an individual's rostrocaudal axis. Regeneration phenotypes depend on how the wound closing occurs using local NSCs, and perfect regeneration replicates development-like processes but takes more than one year. Our findings indicate that newt brain regeneration is supported by modularity of boundary-domain NSCs with self-organizing ability in neighboring fields. © 2018. Published by The Company of Biologists Ltd.

Contribution of magnetic resonance imaging to the diagnosis of multiple sclerosis

International Nuclear Information System (INIS)

Seidl, Z.; Obenberger, J.; Vitak, T.

1996-01-01

The potential of magnetic resonance imaging in the diagnosis of multiple sclerosis (MS) was confirmed on 52 patients. In 25 patients, MS was diagnosed as highly probable, in additional 8 patients this diagnosis was suspected. MR imaging supported the diagnosis in 21 (95%) patients where this disease had been diagnosed as highly probable, and in 3 (38%) suspect patients. Lesions were found most frequently paraventricularly in the white matter of the brain, but also in the deep structures of the white matter of the temporal lobe and below the tentorium (in the cerebellum, pons and mesencephalon). No lesions were found in the optic nerve despite the frequent diagnosis of retrobulbar neuritis. Computerized tomography (CT) was performed in 14 patients; this technique only supported the diagnosis of MS in 3 patients, in all of whom this diagnosis had also been suggested by MR imaging. It is concluded that MR imaging can fully supersede CT as a tool for diagnosing multiple sclerosis. 3 figs., 10 refs

Fahr Syndrome Unknown Complication: Overactive Bladder

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Devrim Tuglu

2014-01-01

Full Text Available A 38-year-old male patient was admitted to our outpatient department because of frequency and urgency incontinence. During evaluation it was detected that the patient was suffering from frequency which was progressive for one year, feeling of incontinence, and urgency incontinence. There was no urologic pathology detected in patient’s medical and family history. Neurologic consultation was requested due to his history of boredom, reluctance to do business, balance disorders, and recession for about 3 years. Brain computerized tomography (CT scan revealed that amorphous calcifications were detected in the bilaterally centrum semiovale, basal ganglia, capsula interna, thalami, mesencephalon, pons and bulbus, and the bilateral cerebellar hemispheres. We have detected spontaneous neurogenic detrusor overactivity without sphincter dyssynergia after evaluating the voiding diary, cystometry, and pressure flow study. We consider the detrusor overactivity which occurred one year after the start of the neurological symptoms as the suprapontine inhibition and damage in the axonal pathways in the Fahr syndrome.

Andrographis Paniculata shows anti-nociceptive effects in an animal model of sensory hypersensitivity associated with migraine.

Science.gov (United States)

Greco, Rosaria; Siani, Francesca; Demartini, Chiara; Zanaboni, Annamaria; Nappi, Giuseppe; Davinelli, Sergio; Scapagnini, Giovanni; Tassorelli, Cristina

2016-01-01

Administration of nitroglycerin (NTG) to rats induces a hyperalgesic condition and neuronal activation of central structures involved in migraine pain. In order to identify therapeutic strategies for migraine pain, we evaluated the anti-nociceptive activity of Andrographis Paniculata (AP), a herbaceous plant, in the hyperalgesia induced by NTG administration in the formalin test. We also analyzed mRNA expression of cytokines in specific brain areas after AP treatment. Male Sprague-Dawley rats were pre-treated with AP extract 30 minutes before NTG or vehicle injection. The data show that AP extract significantly reduced NTG-induced hyperalgesia in phase II of the test, 4 hours after NTG injection. In addition, AP extract reduced IL-6 mRNA expression in the medulla and mesencephalon and also mRNA levels of TNFalpha in the mesencephalic region. These findings suggest that AP extract may be a potential therapeutic approach in the treatment of general pain, and possibly of migraine.

Methamphetamine induces apoptosis in immortalized neural cells: protection by the proto-oncogene, bcl-2.

Science.gov (United States)

Cadet, J L; Ordonez, S V; Ordonez, J V

1997-02-01

Methamphetamine (METH) is an amphetamine analog that produces degeneration of the dopaminergic system in mammals. The neurotoxic effects of the drug are thought to be mediated by oxygen-based free radicals. In the present report, we have used immortalized neural cells obtained from rat mesencephalon in order to further assess the role of oxidative stress in METH-induced neurotoxicity. We thus tested if the anti-death proto-oncogene, bcl-2 could protect against METH-induced cytotoxicity. METH caused dose-dependent loss of cellular viability in control cells while bcl-2-expressing cells were protected against these deleterious effects. Using flow cytometry, immunofluorescent staining, and DNA electrophoresis, we also show that METH exposure can cause DNA strand breaks, chromatin condensation, nuclear fragmentation, and DNA laddering. All these changes were prevented by bcl-2 expression. These observations provide further support for the involvement of oxidative stress in the toxic effects of amphetamine analogs. They also document that METH-induced cytotoxicity is secondary to apoptosis. These findings may be of relevance to the cause(s) of Parkinson's disease which involves degeneration of the nigrostriatal dopaminergic pathway.

Non-classical nuclear localization signal peptides for high efficiency lipofection of primary neurons and neuronal cell lines.

Science.gov (United States)

Ma, H; Zhu, J; Maronski, M; Kotzbauer, P T; Lee, V M-Y; Dichter, M A; Diamond, S L

2002-01-01

Gene transfer into CNS is critical for potential therapeutic applications as well as for the study of the genetic basis of neural development and nerve function. Unfortunately, lipid-based gene transfer to CNS cells is extremely inefficient since the nucleus of these post-mitotic cells presents a significant barrier to transfection. We report the development of a simple and highly efficient lipofection method for primary embryonic rat hippocampal neurons (up to 25% transfection) that exploits the M9 sequence of the non-classical nuclear localization signal of heterogeneous nuclear ribonucleoprotein A1 for targeting beta(2)-karyopherin (transportin-1). M9-assistant lipofection resulted in 20-100-fold enhancement of transfection over lipofection alone for embryonic-derived retinal ganglion cells, rat pheochromocytoma (PC12) cells, embryonic rat ventral mesencephalon neurons, as well as the clinically relevant human NT2 cells or retinoic acid-differentiated NT2 neurons. This technique can facilitate the implementation of promoter construct experiments in post-mitotic cells, stable transformant generation, and dominant-negative mutant expression techniques in CNS cells.

Intermediate filament immunohistochemistry of astroglial cells in the leopard gecko, Eublepharis macularius.

Science.gov (United States)

Lazzari, Maurizio; Franceschini, Valeria

2005-11-01

The distribution of intermediate filament molecular markers, glial fibrillary acidic protein (GFAP) and vimentin, has been studied in the central nervous system (CNS) of the adult leopard gecko, Eublepharis macularius. This immunohistochemical study points out the presence of different astroglial cell types. The main pattern is constituted by ependymal radial glia, which have their cell bodies located in the ependymal layer throughout the brain ventricular system. Radial glia proper or radial astrocytes show their cell bodies displaced from the ependymal layer into a periependymal zone and are observed only in the spinal cord. Star-shaped astrocytes are scarce. They are detected in the ventral and lateral regions of the diencephalon and mesencephalon, in the superficial layer of the optic tectum, in the ventral medulla oblongata, and in the ventral and lateral spinal cord. In the different regions of the CNS, the staining intensity appears not to be identical even in the same cellular type. The results reported in the present study show an heterogeneous feature of the astroglial pattern in E. macularius.

Distribution of the a2, a3, and a5 nicotinic acetylcholine receptor subunits in the chick brain

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Torrão A.S.

1997-01-01

Full Text Available Nicotinic acetylcholine receptors (nAChRs are ionotropic receptors comprised of a and ß subunits. These receptors are widely distributed in the central nervous system, and previous studies have revealed specific patterns of localization for some nAChR subunits in the vertebrate brain. In the present study we used immunohistochemical methods and monoclonal antibodies to localize the a2, a3, and a5 nAChR subunits in the chick mesencephalon and diencephalon. We observed a differential distribution of these three subunits in the chick brain, and showed that the somata and neuropil of many central structures contain the a5 nAChR subunit. The a2 and a3 subunits, on the other hand, exhibited a more restricted distribution than a5 and other subunits previously studied, namely a7, a8 and ß2. The patterns of distribution of the different nAChR subunits suggest that neurons in many brain structures may contain several subtypes of nAChRs and that in a few regions one particular subtype may determine the cholinergic nicotinic responses

Distribution of kappa opioid receptors in the brain of young and old male rats

International Nuclear Information System (INIS)

Maggi, R.; Limonta, P.; Dondi, D.; Martini, L.; Piva, F.

1989-01-01

The experiments to be described have been designed in order to: (a) provide new information on the concentrations of opioid kappa receptors in different regions of the brain of the male rats; and (b) to analyze whether the density of brain kappa receptors might be modified by the process of aging. The concentration of kappa receptors was investigated in the hypothalamus, amygdala, mesencephalon, corpus striatum, hippocampus, thalamus, frontal poles, anterior and posterior cortex collected from male rats of 2 and 19 months of age. 3 H-bremazocine (BRZ) was used as the ligand of kappa receptors, after protection of mu and delta receptors respectively with dihydromorphine and d-ala-d-leu-enkephalin. The results obtained show that: (1) in young male rats, the number of kappa opioid receptors is different in the various brain areas examined. (2) Aging exerts little influence on the number of kappa receptors in the majority of the brain structures considered. However in the amygdala and in the thalamus the number of kappa receptors was increased in old animals

Comparative effects of prolonged administration of cyanide, thiocyanate and chokecherry (Prunus virginiana) to goats.

Science.gov (United States)

Soto-Blanco, B; Stegelmeier, B L; Pfister, J A; Gardner, D R; Panter, K E

2008-04-01

The aim of the present study was to determine and compare the clinical, hematological, biochemical and histopathological changes induced by cyanide, thiocyanate and chokecherry (Prunus virginiana) in goats. Sixteen Boer-Spanish cross-bred female goats were divided into four treatment groups: (1) control, (2) potassium cyanide (KCN) at 3.8 mg kg(-1) day(-1), (3) potassium thiocyanate (KSCN) at 4.5 mg kg(-1) day(-1) and (4) ground frozen chokecherry leaves and flowers at a target dose of 2.5 mg HCN kg(-1) day(-1), all for 4 weeks. Clinical signs were observed in two goats treated with chokecherry. Only sporadic changes were found in the hematological and blood chemical panel. Goats treated with chokecherry and thiocyanate had an increased number of vacuoles in the colloid of thyroid glands. Spongiosis and spheroids were found in the mesencephalon from goats treated with KCN and chokecherry. These findings suggest the thyroid lesions can be attributed to thiocyanate, whereas the effects on the nervous system were most likely caused by cyanide.

Traumatic brain injury and disturbed sleep and wakefulness.

Science.gov (United States)

Baumann, Christian R

2012-09-01

Traumatic brain injury is a frequent condition worldwide, and sleep-wake disturbances often complicate the course after the injuring event. Current evidence suggests that the most common sleep-wake disturbances following traumatic brain injury include excessive daytime sleepiness and posttraumatic hypersomnia, that is, increased sleep need per 24 h. The neuromolecular basis of posttraumatic sleep pressure enhancement is not entirely clear. First neuropathological and clinical studies suggest that impaired hypocretin (orexin) signalling might contribute to sleepiness, but direct or indirect traumatic injury also to other sleep-wake modulating systems in the brainstem and the mesencephalon is likely. Posttraumatic insomnia may be less common than posttraumatic sleepiness, but studies on its frequency revealed conflicting results. Furthermore, insomnia is often associated with psychiatric comorbidities, and some patients with posttraumatic disruption of their circadian rhythm may be misdiagnosed as insomnia patients. The pathophysiology of posttraumatic circadian sleep disorders remains elusive; however, there is some evidence that reduced evening melatonin production due to traumatic brain damage may cause disruption of circadian regulation of sleep and wakefulness.

A novel NDUFV1 gene mutation in complex I deficiency in consanguineous siblings with brainstem lesions and Leigh syndrome.

Science.gov (United States)

Vilain, C; Rens, C; Aeby, A; Balériaux, D; Van Bogaert, P; Remiche, G; Smet, J; Van Coster, R; Abramowicz, M; Pirson, I

2012-09-01

Although deficiency of complex I of the mitochondrial respiratory chain is a frequent cause of encephalopathy in children, only a few mutations have been reported in each of its subunits. In the absence of families large enough for conclusive segregation analysis and of robust functional testing, it is difficult to unequivocally show the causality of the observed mutations and to delineate genotype-phenotype correlations, making additional observations necessary. We observed two consanguineous siblings with an early-onset encephalopathy, medulla, brainstem and mesencephalon lesions on brain magnetic resonance imaging and death before 8 months of age, caused by a complex I deficiency. We used a homozygosity mapping approach and identified a missense mutation in the NDUFV1 gene. The mutation, p.Arg386His, affects a highly conserved residue, contiguous to a cysteine residue known to coordinate an Fe ion. This observation adds to our understanding of complex I deficiency disease. It validates the important role of Arg386 and therefore supports the current molecular model of iron-sulfur clusters in NDUFV1. © 2011 John Wiley & Sons A/S.

Melanin-concentrating hormone: unique peptide neuronal systems in the rat brain and pituitary gland

International Nuclear Information System (INIS)

Zamir, N.; Skofitsch, G.; Bannon, M.J.; Jacobowitz, D.M.

1986-01-01

A unique neuronal system was detected in the rat central nervous system by immunohistochemistry and radioimmunoassay with antibodies to salmon melanin-concentrating hormone (MCH). MCH-like immunoreactive (MCH-LI) cell bodies were confined to the hypothalamus. MCH-LI fibers were found throughout the brain but were most prevalent in hypothalamus, mesencephalon, and pons-medulla regions. High concentrations of MCH-LI were measured in the hypothalamic medial forebrain bundle (MFB), posterior hypothalamic nucleus, and nucleus of the diagonal band. Reversed-phase high-performance liquid chromatography of MFB extracts from rat brain indicate that MCH-like peptide from the rat has a different retention time than that of the salmon MCH. An osmotic stimuls (2% NaCl as drinking water for 120 hr) caused a marked increase in MCH-LI concentrations in the lateral hypothalamus and neurointermediate lobe. The present studies establish the presence of MCH-like peptide in the rat brain. The MCH-LI neuronal system is well situated to coordinate complex functions such as regulation of water intake

Complex neurological symptoms in bilateral thalamic stroke due to Percheron artery occlusion.

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Caruso, Paola; Manganotti, Paolo; Moretti, Rita

2017-01-01

The artery of Percheron is a rare anatomical variant where a single thalamic perforating artery arises from the proximal posterior cerebral artery (P1 segment) between the basilar artery and the posterior communicating artery and supplies the rostral mesencephalon and both paramedian territories of the thalami. Almost one-third of human brains present this variant. Occlusion of the artery of Percheron mostly results in a bilateral medial thalamic infarction, which usually manifests with altered consciousness (including coma), vertical gaze paresis, and cognitive disturbance. The presentation is similar to the "top of the basilar syndrome", and early recognition should be prompted. We describe the case of a young female with this vessel variant who experienced a bilateral thalamic stroke. Magnetic resonance angiography demonstrated bilateral thalamic infarcts and a truncated artery of Percheron. Occlusion of the vessel was presumably due to embolism from a patent foramen ovale. Thrombolysis was performed, with incomplete symptom remission, cognitive impairment, and persistence of speech disorders. Early recognition and treatment of posterior circulation strokes is mandatory, and further investigation for underlying stroke etiologies is needed.

Gender-specific role of mitochondria in the vulnerability of 6-hydroxydopamine-treated mesencephalic neurons.

Science.gov (United States)

Misiak, Magdalena; Beyer, Cordian; Arnold, Susanne

2010-01-01

Many neurodegenerative diseases, such as Morbus Parkinson, exhibit a gender-dependency showing a higher incidence in men than women. Most of the neurodegenerative disorders involve either causally or consequently a dysfunction of mitochondria. Therefore, neuronal mitochondria may demonstrate a gender-specificity with respect to structural and functional characteristics of these organelles during toxic and degenerative processes. The application of 6-OHDA (6-hydroxydopamine) in vitro and in vivo represents a well-accepted experimental model of Parkinson's disease causing Parkinsonian symptoms. Besides the known effects of 6-OHDA on mitochondria and neuronal survivability, we aimed to demonstrate that the mitochondrial neurotoxin affects the morphology and survival of primary dopaminergic and non-dopaminergic neurons in the mesencephalon in a gender-specific manner by influencing the transcription of mitochondrial genes, ATP and reactive oxygen species production. Our data suggest that cell death in response to 6-OHDA is primarily caused due to increased oxidative stress which is more pronounced in male than in female mesencephalic neurons. Copyright © 2010 Elsevier B.V. All rights reserved.

Autoradiographic study of the brain of the brambling (Fringilla montifringilla L.) after 3H-testosterone injection

International Nuclear Information System (INIS)

Luecke, J.; Haase, E.

1980-01-01

The topographic distribution of 3 H-testosterone and/or its metabolites in brains of brablings (Fringilla montifringilla L.) was studied autoradiographically and the intensity of labelling was estimated semiquantitatively. The highest accumulation of radioactivity was found in nuclei of the preoptic region and the hypothalamus. Cells of the nucleus preopticus medialis. Nucleus paraventricularis magnocellularis and nucleus lateralis hypothalami posterioris showed medium or high intensity labelling, while cells of the nucleus preopticus paraventricularis magnocellularis, nucleus hypothalamicus anterior medialis, nucleus hypothalamicus posterior medialis, and the infundibular area contained low or medium concentrations of radioactivity. The role of these nuclei in the gonadal feedback on the hypothalamo-hypophyseal system, in the control of the annual reproductive cycle and as effective sites of testosterone on sexual behaviour are discussed. Moderate accumulations of radioactivity were also observed in the hyperstriatum ventrale of the telencephalon, the nucleus intercollicularis of the mesencephalon and the nucleus nervi hypoglossi of the medulla. These structures are known to influence bird song and other vocalisations. Low labelled cells were found in the periventricular zone of the neostriatum, in the lateral septum, and more irregularly in other areas. The pattern of distribution was similar to that in other birds. (author)

A PET study of effects of chronic 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") on serotonin markers in Göttingen minipig brain

DEFF Research Database (Denmark)

Cumming, Paul; Møller, Mette; Benda, Kjeld

2007-01-01

The psychostimulant 3,4-methylendioxymethamphetamine (MDMA, "ecstasy") evokes degeneration of telencephalic serotonin innervations in rodents, nonhuman primates, and human recreational drug users. However, there has been no alternative to nonhuman primates for studies of the cognitive and neuroch......The psychostimulant 3,4-methylendioxymethamphetamine (MDMA, "ecstasy") evokes degeneration of telencephalic serotonin innervations in rodents, nonhuman primates, and human recreational drug users. However, there has been no alternative to nonhuman primates for studies of the cognitive...... with MDMA (i.m.), administered at a range of doses. In parallel PET studies, [(11)C]WAY-100635 was used to map the distribution of serotonin 5HT(1A) receptors. The acute MDMA treatment in awake pigs evoked 1 degrees C of hyperthermia. MDMA at total doses greater than 20 mg/kg administered over 2-4 days...... reduced the binding potential (pB) of [(11)C]DASB for serotonin transporters in porcine brain. A mean total dose of 42 mg/kg MDMA in four animals evoked a mean 32% decrease in [(11)C]DASB pB in mesencephalon and diencephalon, and a mean 53% decrease in telencephalic structures. However, this depletion...

Outbreaks of Eastern equine encephalitis in northeastern Brazil.

Science.gov (United States)

Silva, Maria L C R; Galiza, Glauco J N; Dantas, Antônio F M; Oliveira, Rafael N; Iamamoto, Keila; Achkar, Samira M; Riet-Correa, Franklin

2011-05-01

Outbreaks of eastern equine encephalitis observed from May 2008 to August 2009 in the Brazilian states of Pernambuco, Ceará, and Paraíba are reported. The disease occurred in 93 farms affecting 229 equids with a case fatality rate of 72.92%. Main clinical signs were circling, depression or hyperexcitability, ataxia, and progressive paralysis with a clinical manifestation period of 3-15 days. Main histologic lesions were a diffuse lymphocytic encephalomyelitis with neuronal death, satellitosis, neuronophagia, and hemorrhages being more severe in the cerebral gray matter of the telencephalon, diencephalon, and mesencephalon. Some animals also had areas of malacia in the telencephalon, thalamus, and basal nuclei. From 1 case, the virus was isolated by mice inoculation, and in other 13 cases was identified as Eastern equine encephalitis virus by semi-nested reverse transcription polymerase chain reaction. After DNA sequencing, all samples were identified as eastern equine encephalitis through the BLASTn analysis, but samples from the Ceará and Paraíba states corresponded to the same cluster, while the sample from the state of Pernambuco corresponded to a different cluster. © 2011 The Author(s)

Glucose metabolism in different regions of the rat brain under hypokinetic stress influence

Science.gov (United States)

Konitzer, K.; Voigt, S.

1980-01-01

Glucose metabolism in rats kept under long term hypokinetic stress was studied in 7 brain regions. Determination was made of the regional levels of glucose, lactate, glutamate, glutamine, aspartate, gamma-aminobutyrate and the incorporation of C-14 from plasma glucose into these metabolites, in glycogen and protein. From the content and activity data the regional glucose flux was approximated quantitatively. Under normal conditions the activity gradient cortex and frontal pole cerebellum, thalamus and mesencephalon, hypothalamus and pons and medulla is identical with that of the regional blood supply (measured with I131 serum albumin as the blood marker). Within the first days of immobilization a functional hypoxia occurred in all brain regions and the utilization of cycle amino acids for protein synthesis was strongly diminished. After the first week of stress the capillary volumes of all regions increased, aerobic glucose metabolism was enhanced (factors 1.3 - 2.0) and the incorporation of glucose C-14 via cycle amino acids into protein was considerably potentiated. The metabolic parameters normalized between the 7th and 11th week of stress. Blood supply and metabolic rate increased most in the hypothalamus.

Utility of a tripolar stimulating electrode for eliciting dopamine release in the rat striatum.

Science.gov (United States)

Bergstrom, B P; Garris, P A

1999-03-01

The present study evaluated tripolar stimulating electrodes for eliciting dopamine release in the rat brain in vivo. Stimulating electrodes were placed either in the medial forebrain bundle or in the ventral mesencephalon associated with the ventral tegmental area and substantia nigra. The concentration of extracellular dopamine was monitored in dopamine terminal fields at 100-ms intervals using fast-scan cyclic voltammetry at carbon-fiber microelectrodes. To characterize the stimulated area, recordings were collected in several striatal regions including the caudate putamen and the core and shell of the nucleus accumbens. The tripolar electrode was equally effective in stimulating dopamine release in medial and lateral regions of the striatum. In contrast, responses evoked by a bipolar electrode were typically greater in one mediolateral edge versus the other. The added size of the tripolar electrode did not appear to cause complications as signals were stable over the course of the experiment (3 h). Subsets of mesostriatal dopamine neurons could also be selectively activated using the tripolar electrode in excellent agreement with previously described topography. Taken together, these results suggested that the tripolar stimulating electrode is well suited for studying the regulation of midbrain dopamine neurons in vivo.

Biochemical evidence for. gamma. -aminobutyrate containing fibres from the nucleus accumbens to the substantia nigra and ventral tegmental area in the rat

Energy Technology Data Exchange (ETDEWEB)

Walaas, I; Fonnum, F

1980-01-01

Glutamate decarboxylase activity, a specific marker for ..gamma..-aminobutyrate-containing neurons, has been analysed in microdissected samples from rat mesencephalon following unilateral electrocoagulations of the nucleus accumbens. This lesion resulted in a consistent decrease of 50% in the enzyme activity in the rostromedial substantia nigra, and a slight, but insignificant decrease (- 15%) in the medial parts of the caudal pars compacta of the substantia nigra. No change was found in the lateral pars compacta or the central pars reticulata. In the ventral tegmental area, the highest activity was found in the rostromedial part, adjacent to the mammillary body. At this level, a significant decrease of 20% was found in the ventral tegmental area on the lesioned side. In contrast, the activities in the medial accessory optic nucleus and the caudal ventral tegmental area adjacent to the interpenduncular nucleus were unchanged. The results indicate that the nucleus accumbens sends ..gamma..-aminobutyrate-containing fibres to the rostromedial substantia nigra and to the rostral ventral tegmental area. The caudal ventral tegmental area, the lateral pars compacta and the central pars reticulata do not receive measurable amounts of such fibres.

MRI findings of radiation encephalopathy of brain stem after radiotherapy for nasopharyngeal cancer

International Nuclear Information System (INIS)

Liang Changhong; Li Guoye; Huang Biao; Huang Meiping; Zheng Junhui; Tan Shaoheng; Zeng Qiongxin

1998-01-01

Purpose: To study MRI findings and clinical manifestation of radiation encephalopathy (RE) of brain stem. Methods: MRI findings and clinical symptoms in 51 patients with RE of brain stem after radiotherapy for nasopharyngeal cancer were reviewed. Results: Clinical symptoms included number weakness or paralysis in the limbs and symptoms of damaged cranial nerves. All lesions appeared hypo- or iso-intense on spin echo(SE) T 1 -weighted images and inhomogeneous and mixed hyper- and iso-intense on Turbo spin echo (TSE) T 2 -weighted images. The lesions were located in mesencephalon, pons, medulla, basilar part of pons, basilar part of pons and medulla oblongata in 2,7,3,9 and 30 patients respectively. The enhancement patterns included irregular rings in 39 patients, spotty in 3 and no enhancement in 9 patients. Mass effect was minimal in all patients. On follow-up MRI, the lesions disappeared in 4 patients, did not change in size and shape in 8 patients and enlarged in 2 patients. Conclusion: MRI could demonstrate the characteristic findings of RE of brain stem. MRI findings sometimes are not consistent with the clinical symptoms

Increase in telencephalic dopamine and cerebellar norepinephrine contents by hydrostatic pressure in goldfish: the possible involvement in hydrostatic pressure-related locomotion.

Science.gov (United States)

Ikegami, Taro; Takemura, Akihiro; Choi, Eunjung; Suda, Atsushi; Tomonaga, Shozo; Badruzzaman, Muhammad; Furuse, Mitsuhiro

2015-10-01

Fish are faced with a wide range of hydrostatic pressure (HP) in their natural habitats. Additionally, freshwater fish are occasionally exposed to rapid changes in HP due to heavy rainfall, flood and/or dam release. Accordingly, variations in HP are one of the most important environmental cues for fish. However, little information is available on how HP information is perceived and transmitted in the central nervous system of fish. The present study examined the effect of HP (water depth of 1.3 m) on the quantities of monoamines and their metabolites in the telencephalon, optic tectum, diencephalon, cerebellum (including partial mesencephalon) and vagal lobe (including medulla oblongata) of the goldfish, Carassius auratus, using high-performance liquid chromatography. HP affected monoamine and metabolite contents in restricted brain regions, including the telencephalon, cerebellum and vagal lobe. In particular, HP significantly increased the levels of dopamine (DA) in the telencephalon at 15 min and that of norepinephrine (NE) in the cerebellum at 30 min. In addition, HP also significantly increased locomotor activity at 15 and 30 min after HP treatment. It is possible that HP indirectly induces locomotion in goldfish via telencephalic DA and cerebellar NE neuronal activity.

Distribution of glycogen phosphorylase and cytochrome oxidase in the central nervous system of the turtle Trachemys dorbigni.

Science.gov (United States)

Partata, W A; Krepsky, A M; Xavier, L L; Marques, M; Achaval, M

1999-10-01

Glycogen phosphorylase (GP) and cytochrome oxidase (CO) activities were mapped histochemically in the brain of the turtle Trachemys dorbigni. In the telencephalon, both activities occurred in the olfactory bulb, in all cortical areas, in the dorsal ventricular ridge, striatum, primordium hippocampi and olfactory tubercle. In the diencephalon, they were identified in some areas of the hypothalamus, and in rotundus and geniculate nuclei. Both reactions were detected in the oculomotor, trochlear, mesencephalic trigeminal nuclei, the nucleus of the posterior commissure, torus semicircularis, substantia nigra and ruber and isthmic nuclei of the mesencephalon. In all layers of the optic tectum GP activity was found, but CO only labelled the stratum griseum centrale. In the medulla oblonga both enzymes appear in the reticular, raphe and vestibular nuclei, locus coeruleus and nuclei of cranial nerves. In the cerebellum, the granular and molecular layers, and the deep cerebellar nuclei were positive for both enzymes. The Purkinje cells were only reactive for CO. In the spinal cord, motor and commissural neurones exhibited a positive reaction for the two enzymes. However, CO also occurred in the marginal nucleus and in the lateral funiculus. These results may be useful as a basis for subsequent studies on turtle brain metabolism.

Primary olfactory projections and the nervus terminalis in the African lungfish: implications for the phylogeny of cranial nerves.

Science.gov (United States)

von Bartheld, C S; Claas, B; Münz, H; Meyer, D L

1988-08-01

Primary olfactory and central projections of the nervus terminalis were investigated by injections of horseradish peroxidase into the olfactory epithelium in the African lungfish. In addition, gonadotropin-releasing hormone (GnRH) immunoreactivity of the nervus terminalis system was investigated. The primary olfactory projections are restricted to the olfactory bulb located at the rostral pole of the telencephalon; they do not extend into caudal parts of the telencephalon. A vomeronasal nerve and an accessory olfactory bulb could not be identified. The nervus terminalis courses through the dorsomedial telencephalon. Major targets include the nucleus of the anterior commissure and the nucleus praeopticus pars superior. some fibers cross to the contralateral side. A few fibers reach the diencephalon and mesencephalon. No label is present in the "posterior root of the nervus terminalis" (= "Pinkus's nerve" or "nervus praeopticus"). GnRH immunoreactivity is lacking in the "anterior root of the nervus terminalis," whereas it is abundant in nervus praeopticus (Pinkus's nerve). These findings may suggest that the nervus terminalis system originally consisted of two distinct cranial nerves, which have fused-in evolution-in most vertebrates. Theories of cranial nerve phylogeny are discussed in the light of the assumed "binerval origin" of the nervus terminalis system.

Regenerative Medicine for Neurological Disorders

Directory of Open Access Journals (Sweden)

Dong-Hyuk Park

2010-01-01

Full Text Available The annual meeting of the American Society for Neural Therapy and Repair (ASNTR has always introduced us to top-notch and up-to-date approaches for regenerative medicine related to neuroscience, ranging from stem cell–based therapy to novel drugs. The 16th ASNTR meeting focused on a variety of different topics, including the unknown pathogenesis or mechanisms of specific neurodegenerative diseases, stem cell biology, and development of novel alternative medicines or devices. Newly developed stem cells, such as amniotic epithelial stem cells and induced pluripotent stem cells, as well as well-known traditional stem cells, such as neural, embryonic, bone marrow mesenchymal, and human umbilical cord blood–derived stem cells, were reported. A number of commercialized stem cells were also covered at this meeting. Fetal neural tissues, such as ventral mesencephalon, striatum, and Schwann cells, were investigated for neurodegenerative diseases or spinal cord injury. A number of studies focused on novel methods for drug monitoring or graft tracking, and combination therapy with stem cells and medicine, such as cytokines or trophic factors. Finally, the National Institutes of Health guidelines for human stem cell research, clinical trials of commercialized stem cells without larger animal testing, and prohibition of medical tourism were big controversial issues that led to heated discussion.

Lunar phase-dependent expression of cryptochrome and a photoperiodic mechanism for lunar phase-recognition in a reef fish, goldlined spinefoot.

Science.gov (United States)

Fukushiro, Masato; Takeuchi, Takahiro; Takeuchi, Yuki; Hur, Sung-Pyo; Sugama, Nozomi; Takemura, Akihiro; Kubo, Yoko; Okano, Keiko; Okano, Toshiyuki

2011-01-01

Lunar cycle-associated physiology has been found in a wide variety of organisms. Recent study has revealed that mRNA levels of Cryptochrome (Cry), one of the circadian clock genes, were significantly higher on a full moon night than on a new moon night in coral, implying the involvement of a photoreception system in the lunar-synchronized spawning. To better establish the generalities surrounding such a mechanism and explore the underlying molecular mechanism, we focused on the relationship between lunar phase, Cry gene expression, and the spawning behavior in a lunar-synchronized spawner, the goldlined spinefoot (Siganus guttatus), and we identified two kinds of Cry genes in this animal. Their mRNA levels showed lunar cycle-dependent expression in the medial part of the brain (mesencephalon and diencephalon) peaking at the first quarter moon. Since this lunar phase coincided with the reproductive phase of the goldlined spinefoot, Cry gene expression was considered a state variable in the lunar phase recognition system. Based on the expression profiles of SgCrys together with the moonlight's pattern of timing and duration during its nightly lunar cycle, we have further speculated on a model of lunar phase recognition for reproductive control in the goldlined spinefoot, which integrates both moonlight and circadian signals in a manner similar to photoperiodic response.

Nonaneurysmal subarachnoid hemorrhage in intramural hematoma of the basilar artery - a case report and literature review

International Nuclear Information System (INIS)

Nedevska, A.; Nakov, V.; Hristov, H.

2012-01-01

Pretruncal (perimesencephalic) nonaneurysmal subarachnoid hemorrhage (SAH) is a benign variant of SAH. Although angiography fails to show a source of the hemorrhage, mild basilar artery narrowing may be observed. The cause of pretruncal nonaneurysmal SAH has not been established. Recent imaging studies have demonstrated that the center of this type of SAH is not around the mesencephalon but is in the prepontine or interpeduncular cistern with the hemorrhage closely associated with the basilar artery. We review the possible sources of hemorrhage in these cisterns and hypothesize that pretruncal nonaneurysmal SAH is caused by a primary intramural hematoma of the basilar artery. Such an intramural hematoma would explain bleeding under low pressure, the location of the hemorrhage anterior to the brainstem, and the typical findings of hemorrhage adjacent to the basilar artery lumen on magnetic resonance imaging and mild basilar artery narrowing on angiography. Hemorrhage in such location is easily found in native computed tomography (CT) images. Crescent, hyperdense thickening of the basilar artery wall is also observed. We have presented this unusual case to highlight the possible mechanism of hematoma formation and underline the importance of MDCT examination in the diagnosis confirmation and also excluding other potentially serious underlying condition that could also lead to non traumatic SAH. (authors)

Cerebral glucose utilization after vasopressin barrel rotation or bicuculline seizures

International Nuclear Information System (INIS)

Wurpel, J.; Dundore, R.; Bryan, R.; Keil, L.; Severs, W.B.

1986-01-01

Intraventricular (ivt) arginine vasopressin (AVP) causes a violent motor behavior termed barrel rotation (BR). AVP-BR is affected by visual/vestibular sensory input and may be related to other CNS motor disorders (seizures). Local cerebral glucose utilization (LCGU) was compared in SD rats during AVP-BR and bicuculline (BIC) seizures. Three groups were used: saline-ivt; AVP-ivt 0.5 μg; BIC-5.5 mg/kg,sc. 14 C-glucose (40 μCI iv) was injected 15 sec. after ivt-saline or AVP or onset of BIC seizures. Rats were decapitated 10 min. after 14 C-glucose. Brains were removed and dissected into 19 regions which were digested and glucose uptake quantified by liquid scintillation counting. LCGU was significantly increased in all CNS areas during BIC seizures vs controls (21-92%; p < 0.05 ANOVA). LCGU exhibits variable (upward arrow, downward arrow) changes in discrete areas during AVP-BR (p < .05). Glucose uptake increased in: cortex-olfactory (21%), sensory (9%), motor (8%) cerebellum-rt (13%) and 1t (17%) hemispheres, vermis (6%); pyramidal tract (6%); mesencephalon (5%); and pons (8%). Two areas decreased LCGU during AVP-BR: auditory cortex (-8%) and hippocampus (-11%). AVP-BR exhibits distinct changes in LCGU vs BIC seizures

Neuron-derived IgG protects dopaminergic neurons from insult by 6-OHDA and activates microglia through the FcγR I and TLR4 pathways.

Science.gov (United States)

Zhang, Jie; Niu, Na; Wang, Mingyu; McNutt, Michael A; Zhang, Donghong; Zhang, Baogang; Lu, Shijun; Liu, Yuqing; Liu, Zhihui

2013-08-01

Oxidative and immune attacks from the environment or microglia have been implicated in the loss of dopaminergic neurons of Parkinson's disease. The role of IgG which is an important immunologic molecule in the process of Parkinson's disease has been unclear. Evidence suggests that IgG can be produced by neurons in addition to its traditionally recognized source B lymphocytes, but its function in neurons is poorly understood. In this study, extensive expression of neuron-derived IgG was demonstrated in dopaminergic neurons of human and rat mesencephalon. With an in vitro Parkinson's disease model, we found that neuron-derived IgG can improve the survival and reduce apoptosis of dopaminergic neurons induced by 6-hydroxydopamine toxicity, and also depress the release of NO from microglia triggered by 6-hydroxydopamine. Expression of TNF-α and IL-10 in microglia was elevated to protective levels by neuron-derived IgG at a physiologic level via the FcγR I and TLR4 pathways and microglial activation could be attenuated by IgG blocking. All these data suggested that neuron-derived IgG may exert a self-protective function by activating microglia properly, and IgG may be involved in maintaining immunity homeostasis in the central nervous system and serve as an active factor under pathological conditions such as Parkinson's disease. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Regulation of differentiation flux by Notch signalling influences the number of dopaminergic neurons in the adult brain

Directory of Open Access Journals (Sweden)

Niurka Trujillo-Paredes

2016-03-01

Full Text Available Notch signalling is a well-established pathway that regulates neurogenesis. However, little is known about the role of Notch signalling in specific neuronal differentiation. Using Dll1 null mice, we found that Notch signalling has no function in the specification of mesencephalic dopaminergic neural precursor cells (NPCs, but plays an important role in regulating their expansion and differentiation into neurons. Premature neuronal differentiation was observed in mesencephalons of Dll1-deficient mice or after treatment with a Notch signalling inhibitor. Coupling between neurogenesis and dopaminergic differentiation was indicated from the coincident emergence of neuronal and dopaminergic markers. Early in differentiation, decreasing Notch signalling caused a reduction in NPCs and an increase in dopaminergic neurons in association with dynamic changes in the proportion of sequentially-linked dopaminergic NPCs (Msx1/2+, Ngn2+, Nurr1+. These effects in differentiation caused a significant reduction in the number of dopaminergic neurons produced. Accordingly, Dll1 haploinsufficient adult mice, in comparison with their wild-type littermates, have a consistent reduction in neuronal density that was particularly evident in the substantia nigra pars compacta. Our results are in agreement with a mathematical model based on a Dll1-mediated regulatory feedback loop between early progenitors and their dividing precursors that controls the emergence and number of dopaminergic neurons.

Evaluation of Possible Prognostic Factors of Fulminant Acute Disseminated Encephalomyelitis (ADEM) on Magnetic Resonance Imaging with Fluid-Attenuated Inversion Recovery (FLAIR) and Diffusion-Weighted Imaging

Energy Technology Data Exchange (ETDEWEB)

Donmez, F.Y.; Aslan, H.; Coskun, M. (Dept. of Radiology, Faculty of Medicine, Baskent Univ., Ankara (Turkey))

2009-04-15

Background: Acute disseminated encephalomyelitis (ADEM) may be a rapidly progressive disease with different clinical outcomes. Purpose: To investigate the radiological findings of fulminant ADEM on diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) images, and to correlate these findings with clinical outcome. Material and Methods: Initial and follow-up magnetic resonance imaging (MRI) scans in eight patients were retrospectively evaluated for distribution of lesions on FLAIR images and presence of hemorrhage or contrast enhancement. DWI of the patients was evaluated as to cytotoxic versus vasogenic edema. The clinical records were analyzed, and MRI results and clinical outcome were correlated. Results: Four of the eight patients died, three had full recovery, and one had residual cortical blindness. The distribution of the hyperintense lesions on FLAIR sequence was as follows: frontal (37.5%), parietal (50%), temporal (37.5%), occipital (62.5%), basal ganglia (50%), pons (37.5%), mesencephalon (37.5%), and cerebellum (50%). Three of the patients who died had brainstem involvement. Two patients had a cytotoxic edema, one of whom died, and the other developed cortical blindness. Six patients had vasogenic edema: three of these patients had a rapid progression to coma and died; three of them recovered. Conclusion: DWI is not always helpful for evaluating the evolution or predicting the outcome of ADEM. However, extension of the lesions, particularly brainstem involvement, may have an influence on the prognosis.

Regional cerebral blood flow in normal pressure hydrocephalus: diagnostic and prognostic aspects

International Nuclear Information System (INIS)

Larsson, A.; Bergh, A.C.; Bilting, M.; Aerlig, AA.; Jacobsson, L.; Stephensen, H.; Wikkelsoe, C.

1994-01-01

Relative regional cerebral blood flow (rrCBF) was measured by SPET using 99m Tc-HMPAO as flow tracer, in 23 patients with normal pressure hydrocephalus (NPH). 1000 MBq 99m Tc-HMPAO was given intravenously and the rrCBF calculated as regional/cerebellar count level ratios. The patients were examined before and 3-12 months after ventriculoperitoneal shunt surgery. rrCBF was also determined in ten healthy aged matched volunteers who served as controls. The NPH patients had decreased rrCBF in the hippocampal regions and in the frontal and parietal white matter as compared to the controls. The frontal/parietal rrCBF ratio correlated with both psychiatric disability and the preoperative degree of incontinence. Decreased flow in frontal white matter, frontoparietal and hippocampal grey matter and a low frontalparietal grey matter flow ratio preoperatively correlated with improvement in both Mini Mental State score and psychiatric disability after shunt surgery. After shunt surgery the rrCBF increased in the mesencephalon, frontal grey and white matter, parietal white matter and hippocampus. The flow increase in hippocampal regions and frontal white matter correlated with improvement in psychiatric symptomatology. The results of this study regarding the frontal and hippocampal rrCBF patterns, and the clinical correlation, support the hypothesis that CBF changes in these regions are of patohphysiological and prognostic importance in NPH. (orig./MG)

Changes in Cerebral Blood Flow during an Alteration in Glycemic State in a Large Non-human Primate (Papio hamadryas sp.).

Science.gov (United States)

Kochunov, Peter; Wey, Hsiao-Ying; Fox, Peter T; Lancaster, Jack L; Davis, Michael D; Wang, Danny J J; Lin, Ai-Ling; Bastarrachea, Raul A; Andrade, Marcia C R; Mattern, Vicki; Frost, Patrice; Higgins, Paul B; Comuzzie, Anthony G; Voruganti, Venkata S

2017-01-01

Changes in cerebral blood flow (CBF) during a hyperglycemic challenge were mapped, using perfusion-weighted MRI, in a group of non-human primates. Seven female baboons were fasted for 16 h prior to 1-h imaging experiment, performed under general anesthesia, that consisted of a 20-min baseline, followed by a bolus infusion of glucose (500 mg/kg). CBF maps were collected every 7 s and blood glucose and insulin levels were sampled at regular intervals. Blood glucose levels rose from 51.3 ± 10.9 to 203.9 ± 38.9 mg/dL and declined to 133.4 ± 22.0 mg/dL, at the end of the experiment. Regional CBF changes consisted of four clusters: cerebral cortex, thalamus, hypothalamus, and mesencephalon. Increases in the hypothalamic blood flow occurred concurrently with the regulatory response to systemic glucose change, whereas CBF declined for other clusters. The return to baseline of hypothalamic blood flow was observed while CBF was still increasing in other brain regions. The spatial pattern of extra-hypothalamic CBF changes was correlated with the patterns of several cerebral networks including the default mode network. These findings suggest that hypothalamic blood flow response to systemic glucose levels can potentially be explained by regulatory activity. The response of extra-hypothalamic clusters followed a different time course and its spatial pattern resembled that of the default-mode network.

Behcet's disease with cerebral vasculitis

International Nuclear Information System (INIS)

Scardamaglia, L.; Desmond, P.M.; Gonzales, M.F.; Bendrups, A.; Brodtmann, A.

2001-01-01

The case presented illustrates the diagnostic dilemma off neurological involvement in Behcet's disease and other inflammatory diseases. 'Psychiatric' symptoms were present for 2 years without abnormalities on SPECT or MRI and without CSF pleocytosis. Even at the time of fitting, no CSF abnormalities were observed. The preceding psychiatric presentations may have been due to cerebral vasculitis that was exacerbated by withdrawal of steroids. Magnetic resonance imaging is currently the most sensitive imaging modality. Lesions are usually in the brainstem, cerebellum, basal ganglia region or periventricular white matter, and the pons and the mesencephalon are commonly affected. In our patient there was no diencephalic or brainstem involvement. The inflammatory process can appear as a very large lesion, with gadolinium enhancement and significant mass effect, as in our patient. Brain magnetic resonance imaging. Postgadolinium-diethylenetriamine pentaacetic acid, axial image shows two large lesions in the right frontal lobe, with the larger, posterior lesion demonstrating vivid ring enhancement. A central nodule is isodense, with the cerebral white matter within the larger lesion. Surrounding low T 1 signal involves the hemispheric white matter without cortical extension and is consistent with vasogenic oedema. Minor mass effect is demonstrated with bowing of the anterior falx cerebri to the left. Biopsy shows prominent fibrinoid necrosis in small calibre postcapillary venules and cerebral white matter. There are surrounding acute and chronic inflammatory cells and nuclear debris, consistent with vasculitis

Musical hallucination associated with hearing loss.

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Sanchez, Tanit Ganz; Rocha, Savya Cybelle Milhomem; Knobel, Keila Alessandra Baraldi; Kii, Márcia Akemi; Santos, Rosa Maria Rodrigues dos; Pereira, Cristiana Borges

2011-01-01

In spite of the fact that musical hallucination have a significant impact on patients' lives, they have received very little attention of experts. Some researchers agree on a combination of peripheral and central dysfunctions as the mechanism that causes hallucination. The most accepted physiopathology of musical hallucination associated to hearing loss (caused by cochlear lesion, cochlear nerve lesion or by interruption of mesencephalon or pontine auditory information) is the disinhibition of auditory memory circuits due to sensory deprivation. Concerning the cortical area involved in musical hallucination, there is evidence that the excitatory mechanism of the superior temporal gyrus, as in epilepsies, is responsible for musical hallucination. In musical release hallucination there is also activation of the auditory association cortex. Finally, considering the laterality, functional studies with musical perception and imagery in normal individuals showed that songs with words cause bilateral temporal activation and melodies activate only the right lobe. The effect of hearing aids on the improvement of musical hallucination as a result of the hearing loss improvement is well documented. It happens because auditory hallucination may be influenced by the external acoustical environment. Neuroleptics, antidepressants and anticonvulsants have been used in the treatment of musical hallucination. Cases of improvement with the administration of carbamazepine, meclobemide and donepezil were reported, but the results obtained were not consistent.

Brain responses associated with consciousness of breathlessness (air hunger).

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Liotti, M; Brannan, S; Egan, G; Shade, R; Madden, L; Abplanalp, B; Robillard, R; Lancaster, J; Zamarripa, F E; Fox, P T; Denton, D

2001-02-13

Little is known about the physiological mechanisms subserving the experience of air hunger and the affective control of breathing in humans. Acute hunger for air after inhalation of CO(2) was studied in nine healthy volunteers with positron emission tomography. Subjective breathlessness was manipulated while end-tidal CO(2-) was held constant. Subjects experienced a significantly greater sense of air hunger breathing through a face mask than through a mouthpiece. The statistical contrast between the two conditions delineated a distributed network of primarily limbic/paralimbic brain regions, including multiple foci in dorsal anterior and middle cingulate gyrus, insula/claustrum, amygdala/periamygdala, lingual and middle temporal gyrus, hypothalamus, pulvinar, and midbrain. This pattern of activations was confirmed by a correlational analysis with breathlessness ratings. The commonality of regions of mesencephalon, diencephalon and limbic/paralimbic areas involved in primal emotions engendered by the basic vegetative systems including hunger for air, thirst, hunger, pain, micturition, and sleep, is discussed with particular reference to the cingulate gyrus. A theory that the phylogenetic origin of consciousness came from primal emotions engendered by immediate threat to the existence of the organism is discussed along with an alternative hypothesis by Edelman that primary awareness emerged with processes of ongoing perceptual categorization giving rise to a scene [Edelman, G. M. (1992) Bright Air, Brilliant Fire (Penguin, London)].

Autoradiographic localization of mu and delta opioid receptors in the mesocorticolimbic dopamine system

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Dilts, R.P. Jr.

1989-01-01

In vitro autoradiographic techniques were coupled with selective chemical lesions of the A10 dopamine cells and intrinsic perikarya of the region to delineate the anatomical localization of mu and delta opioid receptors, as well as, neurotensin receptors. Mu opioid receptors were labeled with {sup 125}I-DAGO. Delta receptors were labeled with {sup 125}I-DPDPE. Neurotensin receptors were labeled with {sup 125}I-NT3. Unilateral lesions of the dopamine perikarya were produced by injections of 6-OHDA administered in the ventral mesencephalon. Unilateral lesions of intrinsic perikarya were induced by injections of quinolinic acid in to the A10 dopamine cell region. Unilateral lesions produced with 6-OHDA resulted in the loss of neurotensin receptors in the A10 region and within the terminal fields. Mu opioid receptors were unaffected by this treatment, but delta opioid receptors increased in the contralateral striatum and nucleus accumbens following 6-OHDA administration. Quinolinic acid produced a reduction of mu opioid receptors within the A10 region with a concomitant reduction in neurotensin receptors in both the cell body region and terminal fields. These results are consistent with a variety of biochemical and behavioral data which suggest the indirect modulation of dopamine transmission by the opioids. In contrast these results strongly indicate a direct modulation of the mesolimbic dopamine system by neurotensin.

Clinical and pathological aspects of chronic Senecio spp. poisoning in sheep

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Paula R. Giaretta

2014-10-01

Full Text Available This paper describes an outbreak of chronic Senecio spp. poisoning in grazing sheep in Rio Grande do Sul, Brazil, causing the death of 10 out of 860 adult sheep. Eight sick ewes were euthanized and necropsied. Cattle from this farm were also affected. Clinical signs included progressive weight loss, apathy and photosensitization. Four out of seven tested sheep had increased gamma-glutamyl transferase serum activity and two of them presented serum elevation of alkaline phosphatase. At necropsy, three out of eight ewes presented slightly irregular toughened livers with multifocal nodules, two out of eight ewes had a whitish liver with thickened fibrotic Glisson's capsule partially adhered to the diaphragm, and three out of eight ewes had smooth and grossly normal livers. Necropsy findings attributed to liver failure included hydropericardium (7/8, ascites (5/8, icterus (2/8, hydrothorax (1/8, and edema of mesentery (1/8. The main hepatic histological findings that allowed the establishment of the diagnosis were megalocytosis, proliferation of bile ducts and fibrosis. Spongy degeneration was observed in the brains of all eight necropsied sheep and was more severe at the cerebellar peduncles, mesencephalon, thalamus, and pons. These are suggested as the portions of election to investigate microscopic lesions of hepatic encephalopathy in sheep with chronic seneciosis. The diagnosis of Senecio spp. poisoning was based on epidemiology, clinical signs, laboratory data, necropsy and histological findings.

Mesencephalic dopaminergic neurons express a repertoire of olfactory receptors and respond to odorant-like molecules.

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Grison, Alice; Zucchelli, Silvia; Urzì, Alice; Zamparo, Ilaria; Lazarevic, Dejan; Pascarella, Giovanni; Roncaglia, Paola; Giorgetti, Alejandro; Garcia-Esparcia, Paula; Vlachouli, Christina; Simone, Roberto; Persichetti, Francesca; Forrest, Alistair R R; Hayashizaki, Yoshihide; Carloni, Paolo; Ferrer, Isidro; Lodovichi, Claudia; Plessy, Charles; Carninci, Piero; Gustincich, Stefano

2014-08-27

The mesencephalic dopaminergic (mDA) cell system is composed of two major groups of projecting cells in the Substantia Nigra (SN) (A9 neurons) and the Ventral Tegmental Area (VTA) (A10 cells). Selective degeneration of A9 neurons occurs in Parkinson's disease (PD) while abnormal function of A10 cells has been linked to schizophrenia, attention deficit and addiction. The molecular basis that underlies selective vulnerability of A9 and A10 neurons is presently unknown. By taking advantage of transgenic labeling, laser capture microdissection coupled to nano Cap-Analysis of Gene Expression (nanoCAGE) technology on isolated A9 and A10 cells, we found that a subset of Olfactory Receptors (OR)s is expressed in mDA neurons. Gene expression analysis was integrated with the FANTOM5 Helicos CAGE sequencing datasets, showing the presence of these ORs in selected tissues and brain areas outside of the olfactory epithelium. OR expression in the mesencephalon was validated by RT-PCR and in situ hybridization. By screening 16 potential ligands on 5 mDA ORs recombinantly expressed in an heterologous in vitro system, we identified carvone enantiomers as agonists at Olfr287 and able to evoke an intracellular Ca2+ increase in solitary mDA neurons. ORs were found expressed in human SN and down-regulated in PD post mortem brains. Our study indicates that mDA neurons express ORs and respond to odor-like molecules providing new opportunities for pharmacological intervention in disease.

Functional integration of grafted neural stem cell-derived dopaminergic neurons monitored by optogenetics in an in vitro Parkinson model.

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Jan Tønnesen

Full Text Available Intrastriatal grafts of stem cell-derived dopamine (DA neurons induce behavioral recovery in animal models of Parkinson's disease (PD, but how they functionally integrate in host neural circuitries is poorly understood. Here, Wnt5a-overexpressing neural stem cells derived from embryonic ventral mesencephalon of tyrosine hydroxylase-GFP transgenic mice were expanded as neurospheres and transplanted into organotypic cultures of wild type mouse striatum. Differentiated GFP-labeled DA neurons in the grafts exhibited mature neuronal properties, including spontaneous firing of action potentials, presence of post-synaptic currents, and functional expression of DA D₂ autoreceptors. These properties resembled those recorded from identical cells in acute slices of intrastriatal grafts in the 6-hydroxy-DA-induced mouse PD model and from DA neurons in intact substantia nigra. Optogenetic activation or inhibition of grafted cells and host neurons using channelrhodopsin-2 (ChR2 and halorhodopsin (NpHR, respectively, revealed complex, bi-directional synaptic interactions between grafted cells and host neurons and extensive synaptic connectivity within the graft. Our data demonstrate for the first time using optogenetics that ectopically grafted stem cell-derived DA neurons become functionally integrated in the DA-denervated striatum. Further optogenetic dissection of the synaptic wiring between grafted and host neurons will be crucial to clarify the cellular and synaptic mechanisms underlying behavioral recovery as well as adverse effects following stem cell-based DA cell replacement strategies in PD.

Suprasellar germ cell tumor in a dog Tumor supra-selar de células germinativas em um cão

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Raquel Rubia Rech

2008-06-01

Full Text Available A case of suprasellar germ cell tumor is described in a 6-year -old Airedale Terrier bitch that presented behavioral changes and abrupt onset of blindness. The neoplasm compressed the ventral surface of the cerebrum from the level of basal ganglia to the mesencephalon. Histologically the neoplasm consisted of nests and trabeculae of round to polygonal cells that occasionally surround tubules and cysts formed by columnar cells. Neoplastic cells are immunopositive for cytokeratin and alpha-fetoprotein. The diagnosis was based on location, histological appearance and on the immunohistochemical staining.É descrito um caso de tumor de células germinativas supra-selar em numa cadela Airedale Terrier de seis anos de idade, que apresentou transtornos do comportamento e aparecimento abrupto de cegueira. O neoplasma comprimia a superfície ventral do cérebro desde a altura dos núcleos basais até o mesencéfalo. Histologicamente, o neoplasma consistia de ninhos e trabéculas de células redondas ou poligonais que ocasionalmente arranjavam-se ao redor de túbulos e cistos formados por células colunares. As células neoplásicas foram positivas na imunoistoquímica para citoqueratina e a-fetoproteína. O diagnóstico foi feito com base na localização do tumor, no seu aspecto histológico e nos resultados da marcação imunoistoquímica.

Astrocytic expression of GFAP and serum levels of IL-1β and TNF-α in rats treated with different pain relievers

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Gisele Ferreira Amaral

Full Text Available ABSTRACT Pro-inflammatory cytokines and glial cells, especially microglial cells, have been implicated in persistent pain sensitization. Less is known about the role of astrocytes in pain regulation. This study aimed to observe the expression of the astrocytic biomarker glial fibrillary acidic protein (GFAP and the serum levels of interleukin 1 beta (IL-1β and tumor necrosis factor alpha (TNF-α after short-term administration of central pain relievers in rats not submitted to noxious stimuli. Male Wistar rats were divided into five groups, receiving for nine days- (1 amitriptyline (Amt-10 mg/kg/day, by gavage; (2 gabapentin (Gb-60 mg/kg/day, by gavage; (3 methadone (Me-4.5 mg/kg/day, intraperitoneal route [IP]; (4 morphine (Mo-10 mg/kg/day, IP; or (5 0.9% saline solution, IP. Brain samples were collected for immunohistochemical study of GFAP expression in the mesencephalon and nucleus accumbens (NAc. The area of GFAP-positive cells was calculated using MetaMorph software and serum levels of IL-1β and TNF-α were measured by enzyme-linked immunosorbent assay. Serum TNF-α levels were decreased in the groups treated with Mo, Me and Gb, but not in the Amt-treated group. IL-1β decreased only in rats treated with Me. The astrocytic expression of GFAP was decreased in the brainstem with all drugs, while it was increased in the NAc with Amt, Me and Mo.

(3H)-dihydrotestosterone in catecholamine neurons of rat brain stem: combined localization by autoradiography and formaldehyde-induced fluorescence

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Heritage, A.S.; Stumpf, W.E.; Sar, M.; Grant, L.D.

1981-01-01

A combined formaldehyde-induced fluorescence (FIF)-autoradiography procedure was used to determine how and where the androgen, dihydrotestosterone (DHT), is associated with catecholamine systems in the rat brain. With this dual localization method, ( 3 H)-DHT target sites can be visualized in relation to catecholamine perikarya and terminals. In the hindbrain, catecholamine neurons adjacent to the fourth ventricle (group A4), the nucleus (n.) olivaris superior (group A5), the n. parabranchialis medialis (group A7), and in the locus coeruleus (group A6) and subcoeruleal regions, as well as in the substantia grisea centralis, concentrate ( 3 H)-DHT in their nuclei. ( 3 H)-DHT target neurons appear to be innervated by numerous catecholamine terminals in the following hindbrain regions: n. motorius dorsalis nervi vagi, n. tractus solitarii, n. commissuralis, n. raphe pallidus, n. olivaris inferior, the ventrolateral portion of the substantia grisea centralis, n. cuneiformis, and the ventrolateral reticular formation in the caudal mesencephalon. In the forebrain, ( 3 H)-DHT concentrates in nuclei of catecholamine neurons located in the n. arcuatus and n. periventricularis (group A12). In addition, ( 3 H)-DHT target neurons appear to be innervated by numerous catecholamine terminals in the following forebrain regions: n. periventricularis rotundocellularis, n. paraventricularis, n. dorsomedialis, n. periventricularis, area retrochiasmatica, n. interstititalis striae terminalis (ventral portion), and n. amygdaloideus centralis. The disclosure of a morphologic association between ( 3 H)-DHT target sites and certain brain catecholamine systems suggests a close functional interdependence between androgens and catecholamines

Potential sources of stem cells as a regenerative therapy for Parkinson's disease

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Abir Oueida El-Sadik

2010-12-01

Full Text Available Abir Oueida El-SadikDepartment of Anatomy and Embryology, Scientific Research Unit, Female Health Science College, King Saud University, Riyadh, Kingdom of Saudi ArabiaAbstract: Stem cells are believed to hold enormous promise as potential replacement therapy in the treatment of neurodegenerative diseases such as Parkinson's disease (PD. Stem cells were investigated to be the alternative therapeutic source capable of differentiating into dopamine (DA neurons. Multiple important signaling factors were recorded for the induction of DA neuronal traits from mouse embryonic stem cells (ESCs such as fibroblast growth factor 8, sonic hedgehog, and Wnt 1. Recent protocols were described for the differentiation of human ESCs into DA neurons, achieving high efficiency of DA neuronal derivation. Despite that, the use of human ESCs is still ethically controversial. The transcription factors necessary for DA neuron development from adult neural stem cells (NSCs, such as Pitx3, Nurr1, En-1, En-2, Lmx1a, Lmx1b, Msx1, and Ngn2, were investigated. In addition to replacement of lost DA neurons, adult NSCs were recorded to provide neuroprotective and neurogenic factors for the mesencephalon. In addition, induced pluripotent stem cells and bone marrow-derived mesenchymal stem cells represent reliable stem cell sources of DA neurons. Future studies are recommended to provide further insight into the regenerative capacity of stem cells needed for the treatment of PD.Keywords: dopamine, embryonic stem cells, neural stem cells, Parkinson's disease, induced pluripotent stem cells, mesenchymal stem cells

Rhombencephalosynapsis as a cause of aqueductal stenosis: an under-recognized association in hydrocephalic children

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Whitehead, Matthew T.; Choudhri, Asim F.; Grimm, John; Nelson, Marvin D.

2014-01-01

Rhombencephalosynapsis is a rare genetic aberration characterized by variable vermian hypoplasia/aplasia in conjunction with united cerebellar hemispheres. Genetic defects in the isthmic organizer at the mesencephalic-metencephalic junction are presumably responsible for the associated aqueductal stenosis. We performed a retrospective review of 20 children with rhombencephalosynapsis to evaluate for and emphasize the association of aqueductal stenosis and hydrocephalus. We retrospectively reviewed the MR and CT images of 20 children (0-11 years old) with rhombencephalosynapsis encountered at two academic children's hospitals. Rhombencephalosynapsis spectrum severity was graded based on pre-existing literature. We analyzed examinations for ventriculomegaly and degree of aqueductal stenosis. The collicular distances were measured from the collicular apices. Imaging studies were also analyzed for malformations of cortical and cerebellar development. Thirteen of the 20 children (65%) with rhombencephalosynapsis presented with clinical or imaging evidence of hydrocephalus and aqueductal stenosis, principally involving the caudal cerebral aqueduct. All children with aqueductal stenosis had collicular fusion. All six children with complete rhombencephalosynapsis had aqueductal stenosis. The cerebral aqueduct varied from normal to stenotic in children with incomplete rhombencephalosynapsis. Corpus callosum dysgenesis was present in four children. Aqueductal stenosis in the setting of rhombencephalosynapsis is an under-recognized cause of noncommunicating hydrocephalus. Our findings support the hypothesis that a defect involving the common gene(s) responsible for the differentiation and development of both the roof plate and midline cerebellar primordium at the mesencephalon/first rhombomere junction may be responsible for the association of aqueductal stenosis and rhombencephalosynapsis. (orig.)

SOX2 and OCT4 mRNA-expressing cells, detected by molecular beacons, localize to the center of neurospheres during differentiation.

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Mirolyuba Ilieva

Full Text Available Neurospheres are used as in vitro assay to measure the properties of neural stem cells. To investigate the molecular and phenotypic heterogeneity of neurospheres, molecular beacons (MBs targeted against the stem cell markers OCT4 and SOX2 were designed, and synthesized with a 2'-O-methyl RNA backbone. OCT4 and SOX2 MBs were transfected into human embryonic mesencephalon derived cells, which spontaneously form neurospheres when grown on poly-L-ornitine/fibronectin matrix and medium complemented with bFGF. OCT4 and SOX2 gene expression were tracked in individual cell using the MBs. Quantitative image analysis every day for seven days showed that the OCT4 and SOX2 mRNA-expressing cells clustered in the centre of the neurospheres cultured in differentiation medium. By contrast, cells at the periphery of the differentiating spheres developed neurite outgrowths and expressed the tyrosine hydroxylase protein, indicating terminal differentiation. Neurospheres cultured in growth medium contained OCT4 and SOX2-positive cells distributed throughout the entire sphere, and no differentiating neurones. Gene expression of SOX2 and OCT4 mRNA detected by MBs correlated well with gene and protein expression measured by qRT-PCR and immunostaining, respectively. These experimental data support the theoretical model that stem cells cluster in the centre of neurospheres, and demonstrate the use of MBs for the spatial localization of specific gene-expressing cells within heterogeneous cell populations.

Investigation of mRNA expression for secreted frizzled-related protein 2 (sFRP2) in chick embryos.

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Lin, Chung-Tien; Lin, Yu-Ting; Kuo, Tzong-Fu

2007-08-01

The roles of secreted frizzled-related protein 2 (sFRP2) in organ development of vertebrate animals are not well understood. We investigated expression of sFRP2 during embryogenesis of Arbor Acre broiler chicken eggs. Expression of sFRP2 was detected in the folds and lateral layer of developing brains. The sFRP2 signals in the developing eye were marked as a circle along the orbit. In younger embryos on days 3-6, the sFRP2 signals were consistent with growth of the sclerotome, suggesting that sFRP2 may be associated with somite development. Furthermore, with the exception of bones, sFRP2 mRNA was detectable in the interdigital tissue of embryos older than eight days as the limbs matured. This revealed that sFRP2 might play a role in myogenesis. In situ hybridization was also used to analyze the expression of sFRP2 in day 3-10 chick embryos. Signals were expressed in the gray matter of the developing brain coelom, including the optic lobe, metencephalon, myelencephalon, mesencephalon and diencephalon. The developing eyes contained an intercellular distribution of sFRP2 in the pigmented layer of the retina and photoreceptors. Furthermore, sFRP2 was expressed in the mantle layer of the neural tube and notochord. Based on these findings, it seems reasonable to suggest that sFRP2 may play an active role in embryogenesis, especially in development of the neural system, eyes, muscles and limbs.

Adult rat bone marrow stromal cells express genes associated with dopamine neurons

International Nuclear Information System (INIS)

Kramer, Brian C.; Woodbury, Dale; Black, Ira B.

2006-01-01

An intensive search is underway to identify candidates to replace the cells that degenerate in Parkinson's disease (PD). To date, no suitable substitute has been found. We have recently found that adult rat bone marrow stromal cells (MSCs) can be induced to assume a neuronal phenotype in vitro. These findings may have particular relevance to the treatment of PD. We now report that adult MSCs express multiple dopaminergic genes, suggesting that they are potential candidates for cell therapy. Using RT-PCR, we have examined families of genes that are associated with the development and/or survival of dopaminergic neurons. MSCs transcribe a variety of dopaminergic genes including patched and smoothened (components of the Shh receptor), Gli-1 (downstream mediator of Shh), and Otx-1, a gene associated with formation of the mesencephalon during development. Furthermore, Shh treatment elicits a 1.5-fold increase in DNA synthesis in cultured MSCs, suggesting the presence of a functional Shh receptor complex. We have also found that MSCs transcribe and translate Nurr-1, a nuclear receptor essential for the development of dopamine neurons. In addition, MSCs express a variety of growth factor receptors including the glycosyl-phosphatidylinositol-anchored ligand-binding subunit of the GDNF receptor, GFRα1, as well as fibroblast growth factor receptors one and four. The expression of genes that are associated with the development and survival of dopamine neurons suggests a potential role for these cells in the treatment of Parkinson's disease

Generation and properties of a new human ventral mesencephalic neural stem cell line

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Villa, Ana; Liste, Isabel; Courtois, Elise T.; Seiz, Emma G.; Ramos, Milagros [Center of Molecular Biology ' Severo Ochoa' , Autonomous University of Madrid-C.S.I.C., Campus Cantoblanco 28049-Madrid (Spain); Meyer, Morten [Department of Anatomy and Neurobiology, Institute of Medical Biology, University of Southern Denmark, Winslowparken 21,st, DK-500, Odense C (Denmark); Juliusson, Bengt; Kusk, Philip [NsGene A/S, Ballerup (Denmark); Martinez-Serrano, Alberto, E-mail: amserrano@cbm.uam.es [Center of Molecular Biology ' Severo Ochoa' , Autonomous University of Madrid-C.S.I.C., Campus Cantoblanco 28049-Madrid (Spain)

2009-07-01

Neural stem cells (NSCs) are powerful research tools for the design and discovery of new approaches to cell therapy in neurodegenerative diseases like Parkinson's disease. Several epigenetic and genetic strategies have been tested for long-term maintenance and expansion of these cells in vitro. Here we report the generation of a new stable cell line of human neural stem cells derived from ventral mesencephalon (hVM1) based on v-myc immortalization. The cells expressed neural stem cell and radial glia markers like nestin, vimentin and 3CB2 under proliferation conditions. After withdrawal of growth factors, proliferation and expression of v-myc were dramatically reduced and the cells differentiated into astrocytes, oligodendrocytes and neurons. hVM1 cells yield a large number of dopaminergic neurons (about 12% of total cells are TH{sup +}) after differentiation, which also produce dopamine. In addition to proneural genes (NGN2, MASH1), differentiated cells show expression of several genuine mesencephalic dopaminergic markers such as: LMX1A, LMX1B, GIRK2, ADH2, NURR1, PITX3, VMAT2 and DAT, indicating that they retain their regional identity. Our data indicate that this cell line and its clonal derivatives may constitute good candidates for the study of development and physiology of human dopaminergic neurons in vitro, and to develop tools for Parkinson's disease cell replacement preclinical research and drug testing.

What does anisotropy measure? Insights from increased and decreased anisotropy in selective fiber tracts in schizophrenia.

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Gabriel A De Erausquin

2013-03-01

Full Text Available Schizophrenia is a common, severe and chronically disabling mental illness of unknown cause. Recent MRI studies have focused attention on white matter abnormalities in schizophrenia using diffusion tensor imaging (DTI. Indices commonly derived from DTI include (a mean diffusivity, independent of direction, (b fractional anisotropy (FA or relative anisotropy (RA, (c axial diffusivity, and (d radial diffusivity. In cerebral white matter, contributions to these indices come from fiber arrangements, degree of myelination, and axonal integrity. Relatively pure deficits in myelin result in a modest increase in radial diffusivity, without affecting axial diffusivity and with preservation of anisotropy. Although schizophrenia is not characterized by gross abnormalities of white matter, it does involve a profound dysregulation of myelin-associated gene expression, reductions in oligodendrocyte numbers, and marked abnormalities in the ultrastructure of myelin sheaths. Since each oligodendrocyte myelinates as many as 40 axon segments, changes in the number of oligodendrocytes, and/or in the integrity of myelin sheaths, and/or axoglial contacts can have a profound impact on signal propagation and the integrity of neuronal circuits. Whereas a number of studies have revealed inconsistent decreases in anisotropy in schizophrenia, we and others have found increased fractional anisotropy in key subcortical tracts associated with the circuits underlying symptom generation in schizophrenia. We review data revealing increased anisotropy in dopaminergic tracts in the mesencephalon of schizophrenics and their unaffected relatives, and discuss the possible biological underpinnings and physiological significance of this finding.

What does anisotropy measure? Insights from increased and decreased anisotropy in selective fiber tracts in schizophrenia.

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Alba-Ferrara, L M; de Erausquin, Gabriel A

2013-01-01

Schizophrenia is a common, severe, and chronically disabling mental illness of unknown cause. Recent MRI studies have focused attention on white matter abnormalities in schizophrenia using diffusion tensor imaging (DTI). Indices commonly derived from DTI include (1) mean diffusivity, independent of direction, (2) fractional anisotropy (FA) or relative anisotropy (RA), (3) axial diffusivity, and (4) radial diffusivity. In cerebral white matter, contributions to these indices come from fiber arrangements, degree of myelination, and axonal integrity. Relatively pure deficits in myelin result in a modest increase in radial diffusivity, without affecting axial diffusivity and with preservation of anisotropy. Although schizophrenia is not characterized by gross abnormalities of white matter, it does involve a profound dysregulation of myelin-associated gene expression, reductions in oligodendrocyte numbers, and marked abnormalities in the ultrastructure of myelin sheaths. Since each oligodendrocyte myelinates as many as 40 axon segments, changes in the number of oligodendrocytes (OLG), and/or in the integrity of myelin sheaths, and/or axoglial contacts can have a profound impact on signal propagation and the integrity of neuronal circuits. Whereas a number of studies have revealed inconsistent decreases in anisotropy in schizophrenia, we and others have found increased FA in key subcortical tracts associated with the circuits underlying symptom generation in schizophrenia. We review data revealing increased anisotropy in dopaminergic tracts in the mesencephalon of schizophrenics and their unaffected relatives, and discuss the possible biological underpinnings and physiological significance of this finding.

Region-specific expression of mitochondrial complex I genes during murine brain development.

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Stefanie Wirtz

Full Text Available Mutations in the nuclear encoded subunits of mitochondrial complex I (NADH:ubiquinone oxidoreductase may cause circumscribed cerebral lesions ranging from degeneration of the striatal and brainstem gray matter (Leigh syndrome to leukodystrophy. We hypothesized that such pattern of regional pathology might be due to local differences in the dependence on complex I function. Using in situ hybridization we investigated the relative expression of 33 nuclear encoded complex I subunits in different brain regions of the mouse at E11.5, E17.5, P1, P11, P28 and adult (12 weeks. With respect to timing and relative intensity of complex I gene expression we found a highly variant pattern in different regions during development. High average expression levels were detected in periods of intense neurogenesis. In cerebellar Purkinje and in hippocampal CA1/CA3 pyramidal neurons we found a second even higher peak during the period of synaptogenesis and maturation. The extraordinary dependence of these structures on complex I gene expression during synaptogenesis is in accord with our recent findings that gamma oscillations--known to be associated with higher cognitive functions of the mammalian brain--strongly depend on the complex I activity. However, with the exception of the mesencephalon, we detected only average complex I expression levels in the striatum and basal ganglia, which does not explain the exquisite vulnerability of these structures in mitochondrial disorders.

Timing of neurodegeneration and beta-amyloid (Abeta) peptide deposition in the brain of aging kokanee salmon.

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Maldonado, Tammy A; Jones, Richard E; Norris, David O

2002-10-01

Brains of kokanee salmon (Oncorhynchus nerka kennerlyi) in one of four reproductive stages (sexually immature, maturing, sexually mature, and spawning) were stained with cresyl violet and silver stain to visualize neurodegeneration. These reproductive stages correlate with increasing somatic aging of kokanee salmon, which die after spawning. Twenty-four regions of each brain were examined. Brains of sexually immature fish exhibited low levels of neurodegeneration, whereas neurodegeneration was more marked in maturing fish and greatest in spawning fish. Neurodegeneration was present in specific regions of the telencephalon, diencephalon, mesencephalon, and rhombencephalon. Pyknotic neurons were observed in all regions previously reported to be immunopositive for A beta. Regions that did not exhibit neurodegeneration during aging included the magnocellular vestibular nucleus, the nucleus lateralis tuberis of the hypothalamus, and Purkinje cells of the cerebellum, all of which also lack A beta; perhaps these regions are neuroprotected. In 14 of 16 brain areas for which data were available on both the increase in A beta deposition and pyknosis, neurodegeneration preceded or appeared more or less simultaneously with A beta production, whereas in only two regions did A beta deposition precede neurodegeneration. This information supports the hypothesis that A beta deposition is a downstream product of neurodegeneration in most brain regions. Other conclusions are that the degree of neurodegeneration varies among brain regions, neurodegeneration begins in maturing fish and peaks in spawning fish, the timing of neurodegeneration varies among brain regions, and some regions do not exhibit accelerated neurodegeneration during aging. Copyright 2002 Wiley Periodicals, Inc.

Rhombencephalosynapsis as a cause of aqueductal stenosis: an under-recognized association in hydrocephalic children

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Whitehead, Matthew T. [University of Tennessee Health Science Center, Department of Radiology, Memphis, TN (United States); Le Bonheur Children' s Hospital, Department of Radiology, Memphis, TN (United States); Le Bonheur Children' s Hospital, Le Bonheur Neuroscience Institute, Memphis, TN (United States); Children' s National Medical Center, Washington, DC (United States); Choudhri, Asim F. [University of Tennessee Health Science Center, Department of Radiology, Memphis, TN (United States); Le Bonheur Children' s Hospital, Le Bonheur Neuroscience Institute, Memphis, TN (United States); University of Tennessee Health Science Center, Department of Neurosurgery, Memphis, TN (United States); Grimm, John; Nelson, Marvin D. [Children' s Hospital Los Angeles, Department of Radiology, Los Angeles, CA (United States)

2014-07-15

Rhombencephalosynapsis is a rare genetic aberration characterized by variable vermian hypoplasia/aplasia in conjunction with united cerebellar hemispheres. Genetic defects in the isthmic organizer at the mesencephalic-metencephalic junction are presumably responsible for the associated aqueductal stenosis. We performed a retrospective review of 20 children with rhombencephalosynapsis to evaluate for and emphasize the association of aqueductal stenosis and hydrocephalus. We retrospectively reviewed the MR and CT images of 20 children (0-11 years old) with rhombencephalosynapsis encountered at two academic children's hospitals. Rhombencephalosynapsis spectrum severity was graded based on pre-existing literature. We analyzed examinations for ventriculomegaly and degree of aqueductal stenosis. The collicular distances were measured from the collicular apices. Imaging studies were also analyzed for malformations of cortical and cerebellar development. Thirteen of the 20 children (65%) with rhombencephalosynapsis presented with clinical or imaging evidence of hydrocephalus and aqueductal stenosis, principally involving the caudal cerebral aqueduct. All children with aqueductal stenosis had collicular fusion. All six children with complete rhombencephalosynapsis had aqueductal stenosis. The cerebral aqueduct varied from normal to stenotic in children with incomplete rhombencephalosynapsis. Corpus callosum dysgenesis was present in four children. Aqueductal stenosis in the setting of rhombencephalosynapsis is an under-recognized cause of noncommunicating hydrocephalus. Our findings support the hypothesis that a defect involving the common gene(s) responsible for the differentiation and development of both the roof plate and midline cerebellar primordium at the mesencephalon/first rhombomere junction may be responsible for the association of aqueductal stenosis and rhombencephalosynapsis. (orig.)

Low doses of alcohol substantially decrease glucose metabolism in the human brain.

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Volkow, Nora D; Wang, Gene-Jack; Franceschi, Dinko; Fowler, Joanna S; Thanos, Panayotis Peter K; Maynard, Laurence; Gatley, S John; Wong, Christopher; Veech, Richard L; Kunos, George; Kai Li, Ting

2006-01-01

Moderate doses of alcohol decrease glucose metabolism in the human brain, which has been interpreted to reflect alcohol-induced decreases in brain activity. Here, we measure the effects of two relatively low doses of alcohol (0.25 g/kg and 0.5 g/kg, or 5 to 10 mM in total body H2O) on glucose metabolism in the human brain. Twenty healthy control subjects were tested using positron emission tomography (PET) and FDG after placebo and after acute oral administration of either 0.25 g/kg, or 0.5 g/kg of alcohol, administered over 40 min. Both doses of alcohol significantly decreased whole-brain glucose metabolism (10% and 23% respectively). The responses differed between doses; whereas the 0.25 g/kg dose predominantly reduced metabolism in cortical regions, the 0.5 g/kg dose reduced metabolism in cortical as well as subcortical regions (i.e. cerebellum, mesencephalon, basal ganglia and thalamus). These doses of alcohol did not significantly change the scores in cognitive performance, which contrasts with our previous results showing that a 13% reduction in brain metabolism by lorazepam was associated with significant impairment in performance on the same battery of cognitive tests. This seemingly paradoxical finding raises the possibility that the large brain metabolic decrements during alcohol intoxication could reflect a shift in the substrate for energy utilization, particularly in light of new evidence that blood-borne acetate, which is markedly increased during intoxication, is a substrate for energy production by the brain.

Penetrating Bihemispheric Traumatic Brain Injury: A Collective Review of Gunshot Wounds to the Head.

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Turco, Lauren; Cornell, David L; Phillips, Bradley

2017-08-01

Head injuries that cross midline structures of the brain are bihemispheric. Other terms have been used to describe such injuries, but bihemispheric is the most accurate and should be standard nomenclature. Bihemispheric head injuries are associated with greater mortality and morbidity than other penetrating traumatic brain injuries (TBIs). Currently, there is a tendency to manage severe gunshot wounds (GSWs) to the head nonoperatively, despite reports of improved outcome in military patients treated aggressively. Thus, controversy exists in the management of civilian TBI. PubMed was searched for query terms, and PRISMA guidelines were used. Studies were selected by relevance and inclusion of data regarding etiology, diagnosis, and management of bihemispheric TBI. Case reports, studies not in English, and records lacking information on mechanism or bihemispheric injuries were excluded. Thirteen studies were included and most contained level IV evidence. The mean mortality rate of all head GSWs was 62% in adults and 32% in children. Bihemispheric GSWs had greater mortality rates of 82% in adults and 60% in children. There was a larger proportion of self-inflicted injury in studies with greater rates of bihemispheric injuries. Bihemispheric injuries have greater mortality rates than other penetrating TBI. Violation of midline brain structures such as the diencephalon and mesencephalon, increased rate of self-inflicted wounds, and lack of a standard management algorithm may increase the lethality of these injuries. Although bihemispheric injuries historically have been considered nonsalvageable, an aggressive surgical approach has been shown to improve outcomes, particularly in the military population. Copyright © 2017 Elsevier Inc. All rights reserved.

PINK1 is necessary for long term survival and mitochondrial function in human dopaminergic neurons.

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Alison Wood-Kaczmar

2008-06-01

Full Text Available Parkinson's disease (PD is a common age-related neurodegenerative disease and it is critical to develop models which recapitulate the pathogenic process including the effect of the ageing process. Although the pathogenesis of sporadic PD is unknown, the identification of the mendelian genetic factor PINK1 has provided new mechanistic insights. In order to investigate the role of PINK1 in Parkinson's disease, we studied PINK1 loss of function in human and primary mouse neurons. Using RNAi, we created stable PINK1 knockdown in human dopaminergic neurons differentiated from foetal ventral mesencephalon stem cells, as well as in an immortalised human neuroblastoma cell line. We sought to validate our findings in primary neurons derived from a transgenic PINK1 knockout mouse. For the first time we demonstrate an age dependent neurodegenerative phenotype in human and mouse neurons. PINK1 deficiency leads to reduced long-term viability in human neurons, which die via the mitochondrial apoptosis pathway. Human neurons lacking PINK1 demonstrate features of marked oxidative stress with widespread mitochondrial dysfunction and abnormal mitochondrial morphology. We report that PINK1 plays a neuroprotective role in the mitochondria of mammalian neurons, especially against stress such as staurosporine. In addition we provide evidence that cellular compensatory mechanisms such as mitochondrial biogenesis and upregulation of lysosomal degradation pathways occur in PINK1 deficiency. The phenotypic effects of PINK1 loss-of-function described here in mammalian neurons provides mechanistic insight into the age-related degeneration of nigral dopaminergic neurons seen in PD.

Expression pattern of cdkl5 during zebrafish early development: implications for use as model for atypical Rett syndrome.

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Vitorino, Marta; Cunha, Nídia; Conceição, Natércia; Cancela, M Leonor

2018-05-11

Atypical Rett syndrome is a child neurodevelopmental disorder induced by mutations in CDKL5 gene and characterized by a progressive regression in development with loss of purposeful use of the hands, slowed brain and head growth, problems with walking, seizures, and intellectual disability. At the moment, there is no cure for this pathology and little information is available concerning animal models capable of mimicking its phenotypes, thus the development of additional animal models should be of interest to gain more knowledge about the disease. Zebrafish has been used successfully as model organism for many human genetic diseases; however, no information is available concerning the spatial and temporal expression of cdkl5 orthologous in this organism. In the present study, we identified the developmental expression patterns of cdkl5 in zebrafish by quantitative PCR and whole-mount in situ hybridization. cdkl5 is expressed maternally at low levels during the first 24 h of development. After that the expression of the gene increases significantly and it starts to be expressed mainly in the nervous system and in several brain structures, such as telencephalon, mesencephalon and diencephalon. The expression patterns of cdkl5 in zebrafish is in accordance with the tissues known to be affected in humans and associated to symptoms and deficits observed in Rett syndrome patients thus providing the first evidence that zebrafish could be an alternative model to study the molecular pathways of this disease as well as to test possible therapeutic approaches capable of rescuing the phenotype.

[Pontomedullary lacerations and concomitant injuries: a review of possible underlying mechanisms].

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Živković, Vladimir; Nikolić, Slobodan

2013-01-01

Anatomically, brainstem is constituted of medulla oblongata, pons and mesencephalon. Traumatic lesions of brainstem most commonly occur on pontomedullary junction. There are several possible mechanisms of pontomedullary lacerations. The first mechanism includes impact to the chin, with or without a skull base fracture, and most often leads to this fatal injury, due to impact force transmission through the jawbone and temporomandibular joint. The second mechanism includes lateral and posterior head impacts with subsequent hinge fractures, where occurrence of pontomedullary lacerations in these cases may depend on the energy of impact, as well as on the exact position of the fracture line, but less so on the head's movement. The third mechanism includes frontoposterior hyperextension of the head, due to frontal impact, concomitant with fractures or dislocations of upper spine. In the fourth mechanism, there is an absence of direct impact to the head, due to the indirect force of action after feet or buttocks-first impact. Most of these cases are accompanied by ring fractures as well. In situations such as these, the impact force is transmitted up the spinal column and upper vertebrae, and telescopically intruded into the skull, causing brainstem laceration. The jawbone and other facial bones can act as shock absorbers, and their fracture could diminish the energy transfer towards the skull and protect the brain and brainstem from injury. In all the cases with pontomedullary laceration posterior neck dissection should be performed during the autopsy, since upper spine injuries are often associated with this type of injury.

Pontomedullary lacerations and concomitant injuries: A review of possible underlying mechanisms

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Živković Vladimir

2013-01-01

Full Text Available Anatomically, brainstem is constituted of medulla oblongata, pons and mesencephalon. Traumatic lesions of brainstem most commonly occur on pontomedullary junction. There are several possible mechanisms of pontomedullary lacerations. The first mechanism includes impact to the chin, with or without a skull base fracture, and most often leads to this fatal injury, due to impact force transmission through the jawbone and temporomandibular joint. The second mechanism includes lateral and posterior head impacts with subsequent hinge fractures, where occurrence of pontomedullary lacerations in these cases may depend on the energy of impact, as well as on the exact position of the fracture line, but less so on the head’s movement. The third mechanism includes frontoposterior hyperextension of the head, due to frontal impact, concomitant with fractures or dislocations of upper spine. In the fourth mechanism, there is an absence of direct impact to the head, due to the indirect force of action after feet or buttocks­first impact. Most of these cases are accompanied by ring fractures as well. In situations such as these, the impact force is transmitted up the spinal column and upper vertebrae, and telescopically intruded into the skull, causing brainstem laceration. The jawbone and other facial bones can act as shock absorbers, and their fracture could diminish the energy transfer towards the skull and protect the brain and brainstem from injury. In all the cases with pontomedullary laceration posterior neck dissection should be performed during the autopsy, since upper spine injuries are often associated with this type of injury. [Projekat Ministarstva nauke Republike Srbije, br. 45005

Putative Adult Neurogenesis in Old World Parrots: The Congo African Grey Parrot (Psittacus erithacus and Timneh Grey Parrot (Psittacus timneh

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Pedzisai Mazengenya

2018-02-01

Full Text Available In the current study, we examined for the first time, the potential for adult neurogenesis throughout the brain of the Congo African grey parrot (Psittacus erithacus and Timneh grey parrot (Psittacus timneh using immunohistochemistry for the endogenous markers proliferating cell nuclear antigen (PCNA, which labels proliferating cells, and doublecortin (DCX, which stains immature and migrating neurons. A similar distribution of PCNA and DCX immunoreactivity was found throughout the brain of the Congo African grey and Timneh grey parrots, but minor differences were also observed. In both species of parrots, PCNA and DCX immunoreactivity was observed in the olfactory bulbs, subventricular zone of the lateral wall of the lateral ventricle, telencephalic subdivisions of the pallium and subpallium, diencephalon, mesencephalon and the rhombencephalon. The olfactory bulb and telencephalic subdivisions exhibited a higher density of both PCNA and DCX immunoreactive cells than any other brain region. DCX immunoreactive staining was stronger in the telencephalon than in the subtelencephalic structures. There was evidence of proliferative hot spots in the dorsal and ventral poles of the lateral ventricle in the Congo African grey parrots at rostral levels, whereas only the dorsal accumulation of proliferating cells was observed in the Timneh grey parrot. In most pallial regions the density of PCNA and DCX stained cells increased from rostral to caudal levels with the densest staining in the nidopallium caudolaterale (NCL. The widespread distribution of PCNA and DCX in the brains of both parrot species suggest the importance of adult neurogenesis and neuronal plasticity during learning and adaptation to external environmental variations.

Red nucleus and rubrospinal tract disorganization in the absence of Pou4f1

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Martinez-Lopez, Jesus E.; Moreno-Bravo, Juan A.; Madrigal, M. Pilar; Martinez, Salvador; Puelles, Eduardo

2015-01-01

The red nucleus (RN) is a neuronal population that plays an important role in forelimb motor control and locomotion. Histologically it is subdivided into two subpopulations, the parvocellular RN (pRN) located in the diencephalon and the magnocellular RN (mRN) in the mesencephalon. The RN integrates signals from motor cortex and cerebellum and projects to spinal cord interneurons and motor neurons through the rubrospinal tract (RST). Pou4f1 is a transcription factor highly expressed in this nucleus that has been related to its specification. Here we profoundly analyzed consequences of Pou4f1 loss-of-function in development, maturation and axonal projection of the RN. Surprisingly, RN neurons are specified and maintained in the mutant, no cell death was detected. Nevertheless, the nucleus appeared disorganized with a strong delay in radial migration and with a wider neuronal distribution; the neurons did not form a compacted population as they do in controls, Robo1 and Slit2 were miss-expressed. Cplx1 and Npas1, expressed in the RN, are transcription factors involved in neurotransmitter release, neuronal maturation and motor function processes among others. In our mutant mice, both transcription factors are lost, suggesting an abnormal maturation of the RN. The resulting altered nucleus occupied a wider territory. Finally, we examined RST development and found that the RN neurons were able to project to the spinal cord but their axons appeared defasciculated. These data suggest that Pou4f1 is necessary for the maturation of RN neurons but not for their specification and maintenance. PMID:25698939

Mitogen-activated protein kinase phosphatase (MKP)-1 as a neuroprotective agent: promotion of the morphological development of midbrain dopaminergic neurons.

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Collins, Louise M; O'Keeffe, Gerard W; Long-Smith, Caitriona M; Wyatt, Sean L; Sullivan, Aideen M; Toulouse, André; Nolan, Yvonne M

2013-06-01

A greater understanding of the mechanisms that promote the survival and growth of dopaminergic neurons is essential for the advancement of cell replacement therapies for Parkinson's disease (PD). Evidence supports a role for the mitogen-activated protein kinase p38 in the demise of dopaminergic neurons, while mitogen-activated protein kinase phosphatase-1 (MKP-1), which negatively regulates p38 activity, has not yet been investigated in this context. Here, we show that MKP-1 is expressed in dopaminergic neurons cultured from E14 rat ventral mesencephalon (VM). When dopaminergic neurons were transfected to overexpress MKP-1, they displayed a more complex morphology than their control counterparts in vitro. Specifically, MKP-1-transfection induced significant increases in neurite length and branching with a maximum increase observed in primary branches. We demonstrate that inhibition of dopaminergic neurite growth induced by treatment of rat VM neurons with the dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA) in vitro is mediated by p38 and is concomitant with a significant and selective decrease in MKP-1 expression in these neurons. We further show that overexpression of MKP-1 in dopaminergic neurons contributes to neuroprotection against the effects of 6-OHDA. Collectively, we report that MKP-1 can promote the growth and elaboration of dopaminergic neuronal processes and can help protect them from the neurotoxic effects of 6-OHDA. Thus, we propose that strategies aimed at augmenting MKP-1 expression or activity may be beneficial in protecting dopaminergic neurons and may provide potential therapeutic approaches for PD.

Autoradiographic localization of delta opioid receptors within the mesocorticolimbic dopamine system using radioiodinated (2-D-penicillamine, 5-D-penicillamine)enkephalin ( sup 125 I-DPDPE)

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Dilts, R.P.; Kalivas, P.W. (Washington State Univ., Pullman (USA))

1990-01-01

The enkephalin analog (2-D-penicillamine, 5-D-penicillamine)enkephalin was radioiodinated (125I-DPDPE) and shown to retain a pharmacological selectivity characteristic of the delta opioid receptor in in vitro binding studies. The distributions of 125I-DPDPE binding, using in vitro autoradiographic techniques, were similar to those previously reported for the delta opioid receptor. The nucleus accumbens, striatum, and medial prefrontal cortex contain dense gradients of 125I-DPDPE binding in regions known to receive dopaminergic afferents emanating from the mesencephalic tegmentum. Selective chemical lesions of the ventral tegmental area and substantia nigra were employed to deduce the location of the 125I-DPDPE binding within particular regions of the mesocorticolimbic dopamine system. Unilateral lesions of dopamine perikarya (A9 and A10) within the ventral tegmental area and substantia nigra produced by mesencephalic injection of 6-hydroxydopamine resulted in significant (20-30%) increases in 125I-DPDPE binding contralateral to the lesion within the striatum and nucleus accumbens. Lesions of the perikarya (dopaminergic and nondopaminergic) of the ventral tegmental area, induced by quinolinic acid injections, caused increases of less magnitude within these same nuclei. No significant alterations in 125I-DPDPE binding were observed within the mesencephalon as a result of either treatment. The specificity of the lesions was confirmed by immunocytochemistry for tyrosine hydroxylase. These results suggest that the enkephalins and opioid agonists acting through delta opioid receptors do not directly modulate dopaminergic afferents but do regulate postsynaptic targets of the mesocorticolimbic dopamine system.

Abuse potential and adverse cognitive effects of mitragynine (kratom).

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Yusoff, Nurul H M; Suhaimi, Farah W; Vadivelu, Raja K; Hassan, Zurina; Rümler, Anne; Rotter, Andrea; Amato, Davide; Dringenberg, Hans C; Mansor, Sharif M; Navaratnam, Visweswaran; Müller, Christian P

2016-01-01

Mitragynine is the major psychoactive alkaloid of the plant kratom/ketum. Kratom is widely used in Southeast Asia as a recreational drug, and increasingly appears as a pure compound or a component of 'herbal high' preparations in the Western world. While mitragynine/kratom may have analgesic, muscle relaxant and anti-inflammatory effects, its addictive properties and effects on cognitive performance are unknown. We isolated mitragynine from the plant and performed a thorough investigation of its behavioural effects in rats and mice. Here we describe an addictive profile and cognitive impairments of acute and chronic mitragynine administration, which closely resembles that of morphine. Acute mitragynine has complex effects on locomotor activity. Repeated administration induces locomotor sensitization, anxiolysis and conditioned place preference, enhances expression of dopamine transporter- and dopamine receptor-regulating factor mRNA in the mesencephalon. While there was no increase in spontaneous locomotor activity during withdrawal, animals showed hypersensitivity towards small challenging doses for up to 14 days. Severe somatic withdrawal signs developed after 12 hours, and increased level of anxiety became evident after 24 hours of withdrawal. Acute mitragynine independently impaired passive avoidance learning, memory consolidation and retrieval, possibly mediated by a disruption of cortical oscillatory activity, including the suppression of low-frequency rhythms (delta and theta) in the electrocorticogram. Chronic mitragynine administration led to impaired passive avoidance and object recognition learning. Altogether, these findings provide evidence for an addiction potential with cognitive impairments for mitragynine, which suggest its classification as a harmful drug. © 2014 Society for the Study of Addiction.

Putative Adult Neurogenesis in Old World Parrots: The Congo African Grey Parrot (Psittacus erithacus) and Timneh Grey Parrot (Psittacus timneh).

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Mazengenya, Pedzisai; Bhagwandin, Adhil; Manger, Paul R; Ihunwo, Amadi O

2018-01-01

In the current study, we examined for the first time, the potential for adult neurogenesis throughout the brain of the Congo African grey parrot ( Psittacus erithacus ) and Timneh grey parrot ( Psittacus timneh ) using immunohistochemistry for the endogenous markers proliferating cell nuclear antigen (PCNA), which labels proliferating cells, and doublecortin (DCX), which stains immature and migrating neurons. A similar distribution of PCNA and DCX immunoreactivity was found throughout the brain of the Congo African grey and Timneh grey parrots, but minor differences were also observed. In both species of parrots, PCNA and DCX immunoreactivity was observed in the olfactory bulbs, subventricular zone of the lateral wall of the lateral ventricle, telencephalic subdivisions of the pallium and subpallium, diencephalon, mesencephalon and the rhombencephalon. The olfactory bulb and telencephalic subdivisions exhibited a higher density of both PCNA and DCX immunoreactive cells than any other brain region. DCX immunoreactive staining was stronger in the telencephalon than in the subtelencephalic structures. There was evidence of proliferative hot spots in the dorsal and ventral poles of the lateral ventricle in the Congo African grey parrots at rostral levels, whereas only the dorsal accumulation of proliferating cells was observed in the Timneh grey parrot. In most pallial regions the density of PCNA and DCX stained cells increased from rostral to caudal levels with the densest staining in the nidopallium caudolaterale (NCL). The widespread distribution of PCNA and DCX in the brains of both parrot species suggest the importance of adult neurogenesis and neuronal plasticity during learning and adaptation to external environmental variations.

Magnetic Resonance Imaging of a Case of Central Neurocytoma.

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Dedushi, Kreshnike; Kabashi, Serbeze; Ugurel, Mehmet Sahin; Ramadani, Naser; Mucaj, Sefedin; Zeqiraj, Kamber

2016-12-01

The purpose of this study is to investigate the MRI features of central neurocytoma. A 45 year old man with 3 months of worsening daily headaches. These headaches were diffuse, lasted for several hours, and mostly occurred in the morning. She was initially diagnosed and treated for migraines but later he had epileptic attack and diplopia and neurolog recomaded MRI. precontrast MRI; TSE/T2Wsequence in axial/coronal planes; 3D-Hi-resolution T1W sagittal; FLAIR/T2W axial; FLAIR/T2W and Flash/T2W oblique coronal plane (perpendicular to temporal lobes) GRE/T2W axial plane for detection of heme products. Post-contrast TSE/T1W sequence in axial, coronal and sagittal planes. Diffusion weighted and ADC mapping MRI images for EPI sequence in axial plane. A 23x12mm heterogeneous mass within aqueductus cerebri, with calcified and hemorrhagic foci and extending downwards till fourth ventricle. It's originating from the right paramedian posterior aqueductal wall (tectum), and also extending to and involving the tegmentum of mesencephalon at its right paramedian aspect. CSF flow obstruction secondary to described aqueductal mass, with resultant triventricular hydrocephalus). Marked transependymal CSF leak can be noted at periventricular white matter, secondary to severe hydrocephalus. After IV injection of contrast media, this mass shows mild-to-moderate heterogenous speckled enhancement. MRI is helpful in defining tumor extension, which is important in preoperative planning. Although IN is a relatively rare lesion, it should be considered in the differential diagnosis of intraventricular lesions in the presence of such typical MR findings. However, a definitive diagnosis requires immunochemical study and electron microscopy.

Autologous Adrenal Medullary, Fetal Mesencephalic, and Fetal Adrenal Brain Transplantation in Parkinson's Disease: A Long-Term Postoperative Follow-Up

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Madrazo, Ignacio; Franco-Bourland, Rebecca; Aguilera, Maricarmen; Ostrosky-Solis, Feggy; Madrazo, Mario; Cuevas, Carlos; Catrejon, Hugo; Guizar-Zahagun, Gabriel; Magallon, Eduardo

1991-01-01

We report on the clinical status of 5 patients with Parkinson's disease (PD) 3 years after autologous adrenal medullary (AM)-to-caudate nucleus (CN) implanfion, and of 2 PD patients, 2 years after fetal ventral mesencephalon (VM)- and fetal adrenal (A)-to-CN homotransplantation. Current clinical evaluation of 4 of the AM grafted patients revealed sustained bilateral amelioration of their PD signs, most notably of rgidity, postural imbalance and gait disturbances, resulting in a substantial improvement in their quality of life. the disease-related dystonia of one of them disappeared only 2 years after surgery. The levodopa requirements of 2 of these patients and the anticholinergic therapy of another have been reduced. In agreement with the satisfactory clinical evaluation of these 4 patients, their neuropsychological and electrophysiological improvements, initially registered 3 months after surgery, have been maintained for 3 years. After 1 year of significant recovery, the 5th patient of this group has almost returned to her preoperative state. The 2 homotransplanted patients also showed sustained bilateral improvement of their PD signs. Two years after surgery, the most improved signs of the fetal VM case were rigidity, bradykinesia, postural imbalance, gait disturbances and facial expression. The fetal A case has only shown amelioration of rigidity and bradykinesia. Neither of them has shown significant neuropsychological changes. Their current levodopa requirements are less than before surgery. The improvements shown here by PD patients after brain tissue grafts go beyond those obtained using any other therapeutic approach, when levodopa fails. Although more studies and the development of these procedures are obviously required, these initial human trials appear to be resisting the test of time. PMID:1782251

Regional oligodendrocytopathy and astrocytopathy precede myelin loss and blood-brain barrier disruption in a murine model of osmotic demyelination syndrome.

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Bouchat, Joanna; Couturier, Bruno; Marneffe, Catherine; Gankam-Kengne, Fabrice; Balau, Benoît; De Swert, Kathleen; Brion, Jean-Pierre; Poncelet, Luc; Gilloteaux, Jacques; Nicaise, Charles

2018-03-01

The osmotic demyelination syndrome (ODS) is a non-primary inflammatory disorder of the central nervous system myelin that is often associated with a precipitous rise of serum sodium concentration. To investigate the physiopathology of ODS in vivo, we generated a novel murine model based on the abrupt correction of chronic hyponatremia. Accordingly, ODS mice developed impairments in brainstem auditory evoked potentials and in grip strength. At 24 hr post-correction, oligodendrocyte markers (APC and Cx47) were downregulated, prior to any detectable demyelination. Oligodendrocytopathy was temporally and spatially correlated with the loss of astrocyte markers (ALDH1L1 and Cx43), and both with the brain areas that will develop demyelination. Oligodendrocytopathy and astrocytopathy were confirmed at the ultrastructural level and culminated with necroptotic cell death, as demonstrated by pMLKL immunoreactivity. At 48 hr post-correction, ODS brains contained pathognomonic demyelinating lesions in the pons, mesencephalon, thalamus and cortical regions. These damages were accompanied by blood-brain barrier (BBB) leakages. Expression levels of IL-1β, FasL, TNFRSF6 and LIF factors were significantly upregulated in the ODS lesions. Quiescent microglial cells type A acquired an activated type B morphology within 24 hr post-correction, and reached type D at 48 hr. In conclusion, this murine model of ODS reproduces the CNS demyelination observed in human pathology and indicates ambiguous causes that is regional vulnerability of oligodendrocytes and astrocytes, while it discards BBB disruption as a primary cause of demyelination. This study also raises new queries about the glial heterogeneity in susceptible brain regions as well as about the early microglial activation associated with ODS. © 2017 Wiley Periodicals, Inc.

Anatomical and MRI relations of the cerebral aqueduct to the adjacent parts of the brain and calvaria

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Stanković Gordana

2017-01-01

Full Text Available Introducton/Objective. Insufficiency of relevant anatomic data and great neurological and neurosurgical significance were the reasons for this study with scientific and practical implications. The purpose was to determine, at the transverse in situ section of the head, the position and relations of the sylvian aqueduct of the mesencephalon by measuring its distances from particular brain and calvaria structures. Also, the aim was to determine the same distances according to axial sections by using MRI. Methods. The material consisted of twenty autopsy human heads. The section of the head was made at the level of the tentorial hiatus and the midbrain. After that, we measured the distances between the cerebral aqueduct and a posterior border of the optic chiasm, b upper border of the dorsum sellae, c terminal bifurcation of the basilar artery, d beginning of the straight sinus, e internal occipital protuberance, f tentorial edge (lateral from the aqueduct, and g internal surface of the calvaria (lateral to the aqueduct. We determined the same distances by the MRI system. The measurements were made in 37 subjects. Results. The numerical data obtained by this study will be of benefit to neurosurgeons in choosing a surgical approach to the contents of the incisural space, and to neurologists for the exact localization of the lesion and interpretation of certain signs and symptoms. Conclusion. The results of a detailed examination of the sylvian aqueduct position and relations have shown that the use of MRI is the morphometric method of choice, because it is more precise for all the parameters monitored than in situ measurements. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 175030

The right thalamus may play an important role in anesthesia-awakening regulation in frogs

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Yanzhu Fan

2018-03-01

Full Text Available Background Previous studies have shown that the mammalian thalamus is a key structure for anesthesia-induced unconsciousness and anesthesia-awakening regulation. However, both the dynamic characteristics and probable lateralization of thalamic functioning during anesthesia-awakening regulation are not fully understood, and little is known of the evolutionary basis of the role of the thalamus in anesthesia-awakening regulation. Methods An amphibian species, the South African clawed frog (Xenopus laevis was used in the present study. The frogs were immersed in triciane methanesulfonate (MS-222 for general anesthesia. Electroencephalogram (EEG signals were recorded continuously from both sides of the telencephalon, diencephalon (thalamus and mesencephalon during the pre-anesthesia stage, administration stage, recovery stage and post-anesthesia stage. EEG data was analyzed including calculation of approximate entropy (ApEn and permutation entropy (PE. Results Both ApEn and PE values differed significantly between anesthesia stages, with the highest values occurring during the awakening period and the lowest values during the anesthesia period. There was a significant correlation between the stage durations and ApEn or PE values during anesthesia-awakening cycle primarily for the right diencephalon (right thalamus. ApEn and PE values for females were significantly higher than those for males. Discussion ApEn and PE measurements are suitable for estimating depth of anesthesia and complexity of amphibian brain activity. The right thalamus appears physiologically positioned to play an important role in anesthesia-awakening regulation in frogs indicating an early evolutionary origin of the role of the thalamus in arousal and consciousness in land vertebrates. Sex differences exist in the neural regulation of general anesthesia in frogs.

Neuropathogenesis of a highly pathogenic avian influenza virus (H7N1 in experimentally infected chickens

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Chaves Aida J

2011-10-01

Full Text Available Abstract In order to understand the mechanism of neuroinvasion of a highly pathogenic avian influenza virus (HPAIV into the central nervous system (CNS of chickens, specific pathogen free chickens were inoculated with a H7N1 HPAIV. Blood, cerebrospinal fluid (CSF, nasal cavity and brain tissue samples were obtained from 1 to 4 days post-inoculation (dpi of infected and control chickens. Viral antigen topographical distribution, presence of influenza A virus receptors in the brain, as well as, the role of the olfactory route in virus CNS invasion were studied using different immunohistochemistry techniques. Besides, viral RNA load in CSF and blood was quantified by means of a quantitative real-time reverse transcription-polymerase chain reaction. Viral antigen was observed widely distributed in the CNS, showing bilateral and symmetrical distribution in the nuclei of the diencephalon, mesencephalon and rhombencephalon. Viral RNA was detected in blood and CSF at one dpi, indicating that the virus crosses the blood-CSF-barrier early during infection. This early dissemination is possibly favoured by the presence of Siaα2,3 Gal and Siaα2,6 Gal receptors in brain vascular endothelial cells, and Siaα2,3 Gal receptors in ependymal and choroid plexus cells. No viral antigen was observed in olfactory sensory neurons, while the olfactory bulb showed only weak staining, suggesting that the virus did not use this pathway to enter into the brain. The sequence of virus appearance and the topographical distribution of this H7N1 HPAIV indicate that the viral entry occurs via the haematogenous route, with early and generalized spreading through the CSF.

Neuropathogenesis of a highly pathogenic avian influenza virus (H7N1) in experimentally infected chickens.

Science.gov (United States)

Chaves, Aida J; Busquets, Núria; Valle, Rosa; Rivas, Raquel; Vergara-Alert, Júlia; Dolz, Roser; Ramis, Antonio; Darji, Ayub; Majó, Natàlia

2011-10-07

In order to understand the mechanism of neuroinvasion of a highly pathogenic avian influenza virus (HPAIV) into the central nervous system (CNS) of chickens, specific pathogen free chickens were inoculated with a H7N1 HPAIV. Blood, cerebrospinal fluid (CSF), nasal cavity and brain tissue samples were obtained from 1 to 4 days post-inoculation (dpi) of infected and control chickens. Viral antigen topographical distribution, presence of influenza A virus receptors in the brain, as well as, the role of the olfactory route in virus CNS invasion were studied using different immunohistochemistry techniques. Besides, viral RNA load in CSF and blood was quantified by means of a quantitative real-time reverse transcription-polymerase chain reaction. Viral antigen was observed widely distributed in the CNS, showing bilateral and symmetrical distribution in the nuclei of the diencephalon, mesencephalon and rhombencephalon. Viral RNA was detected in blood and CSF at one dpi, indicating that the virus crosses the blood-CSF-barrier early during infection. This early dissemination is possibly favoured by the presence of Siaα2,3 Gal and Siaα2,6 Gal receptors in brain vascular endothelial cells, and Siaα2,3 Gal receptors in ependymal and choroid plexus cells. No viral antigen was observed in olfactory sensory neurons, while the olfactory bulb showed only weak staining, suggesting that the virus did not use this pathway to enter into the brain. The sequence of virus appearance and the topographical distribution of this H7N1 HPAIV indicate that the viral entry occurs via the haematogenous route, with early and generalized spreading through the CSF.

Morfologia da artéria cerebelar superior do macaco prego (Cebus apella L., 1766: divisões e anastomoses Morphology of the superior cerebellar artery of the “macaco prego” (Cebus paella L., 1766: divisions and anastomoses

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Rosimeire Alves da Silva

2002-04-01

Full Text Available Dando continuidade a estudos já existentes na área de mapeamento da vascularização cerebral do Cebus apella e considerando a semelhança desse animal com outros primatas descritos, inclusive os humanos, estudou-se a morfologia das artérias cerebelares superiores, que destinam a irrigar a superfície superior do cerebelo. 57 hemisférios cerebelares foram injetados com látex corado e fixados em solução de formol a 10%, dissecados sob mesoscopia de luz com microdissecações. As artérias cerebelares superiores são simétricas em 84,21% e assimétricas em 7,01%, ramificam-se em 4 ramos: sendo 1 para o mesencéfalo e 3 troncos principais para a superfície superior do cerebelo e regiões anterior dessa superfície. Estas artérias terminam na fissura póstero-superior ou pós-semilunar após emitir vários ramos colaterais de hierarquia decrescente de calibreIn order to continue studies already done in the area of mapping the cerebral vascularization of Cebus paella and taking into consideration the resemblance of this animal with other primates described, humans included, we studied the morphology of the superior cerebellar arteries determined to perfuse the superior surface of the cerebellum. Fifty-seven cerebellar hemispheres were injected with stained latex, fixed in 10% formol solution and dissected under light mesoscopy. The superior cerebellar arteries are symmetrical in 84,21% and asymmetrical in 7,01%, and give off four branches, one to the mesencephalon and three mains branches to the upper surface of the cerebellum and its anterior portion. These arteries end in the posterior superior or post-semilunar fissure, after giving off many collaterals of decreasing diameter

Mesencephalic substantia nigra and Parkinson's disease: spin-echo and inversion-recovery MRI evaluation

International Nuclear Information System (INIS)

Michaux, Ruben P.

2004-01-01

Objective: To comparatively assess the images of the mesencephalic substantia nigra (mSN) obtained with FSE (PD and T2) and IR (STIR; T1; WMS and GMS) sequences in patients with Parkinson's disease (PKD) and normal volunteers. Methods: We studied 8 normal volunteers (N group) and 8 patients (PKD groups) of similar age, both men and women, with a clinical diagnosis of PKD. We obtained axial oblique images of the mesencephalon with FSE PD and T2 sequences; Inversion-Recovery (IR) with a short inversion time (STIR); T1 weighted (IR-T1 phase reconstruction) with white matter signal suppression (IR-WMS) and gray matter signal suppression (IR-GMS). Average values were measured for: a) normalized signal intensity; b) thickness; and c) area of the mSN in each sequence and group. A statistical analysis of the values obtained for each of the variables was performed for both groups (Student and Welch correlation tests), comparing the results of the intra an inter-group sequences. A p value 0.05). Images obtained with IR-WMS and GMS sequences showed significant differences between the three variables assessed, particularly thickness and area (p<0.01), and also showed a posterolateral-anteromedial gradient in the mSN alteration in patients with PKD or recent onset and chronic evolution. Conclusions: The T2 weighted FSE sequences are not useful for the assessment of mSN, whereas PD, STIR and IR-T1 sequences allow to delineate it more accurately, without morphological differences (thickness and area), or signal intensity differences among the groups assessed. The WMS and GMS sequences showed statistically significant differences in the assessment of thickness, area and the signal intensity of the mSN, and may hence be useful for diagnosis. (author)

Putative adult neurogenesis in two domestic pigeon breeds (Columba livia domestica): racing homer versus utility carneau pigeons.

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Mazengenya, Pedzisai; Bhagwandin, Adhil; Nkomozepi, Pilani; Manger, Paul R; Ihunwo, Amadi O

2017-07-01

Generation of neurons in the brains of adult birds has been studied extensively in the telencephalon of song birds and few studies are reported on the distribution of PCNA and DCX in the telencephalon of adult non-song learning birds. We report here on adult neurogenesis throughout the brains of two breeds of adult domestic pigeons (Columba livia domestica), the racing homer and utility carneau using endogenous immunohistochemical markers proliferating cell nuclear antigen (PCNA) for proliferating cells and doublecortin (DCX) for immature and migrating neurons. The distribution of PCNA and DCX immunoreactivity was very similar in both pigeon breeds with only a few minor differences. In both pigeons, PCNA and DCX immunoreactivity was observed in the olfactory bulbs, walls of the lateral ventricle, telencephalic subdivisions of the pallium and subpallium, diencephalon, mesencephalon and cerebellum. Generally, the olfactory bulbs and telencephalon had more PCNA and DCX cells than other regions. Two proliferative hotspots were evident in the dorsal and ventral poles of the lateral ventricles. PCNA- and DCX-immunoreactive cells migrated radially from the walls of the lateral ventricle into the parenchyma. In most telencephalic regions, the density of PCNA- and DCX-immunoreactive cells increased from rostral to caudal, except in the mesopallium where the density decreased from rostral to middle levels and then increased caudally. DCX immunoreactivity was more intense in fibres than in cell bodies and DCX-immunoreactive cells included small granular cells, fusiform bipolar cells, large round and or polygonal multipolar cells. The similarity in the distribution of proliferating cells and new neurons in the telencephalon of the two breeds of pigeons may suggest that adult neurogenesis is a conserved trait as an ecological adaptation irrespective of body size.

Putative adult neurogenesis in two domestic pigeon breeds (Columba livia domestica: racing homer versus utility carneau pigeons

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Pedzisai Mazengenya

2017-01-01

Full Text Available Generation of neurons in the brains of adult birds has been studied extensively in the telencephalon of song birds and few studies are reported on the distribution of PCNA and DCX in the telencephalon of adult non-song learning birds. We report here on adult neurogenesis throughout the brains of two breeds of adult domestic pigeons (Columba livia domestica, the racing homer and utility carneau using endogenous immunohistochemical markers proliferating cell nuclear antigen (PCNA for proliferating cells and doublecortin (DCX for immature and migrating neurons. The distribution of PCNA and DCX immunoreactivity was very similar in both pigeon breeds with only a few minor differences. In both pigeons, PCNA and DCX immunoreactivity was observed in the olfactory bulbs, walls of the lateral ventricle, telencephalic subdivisions of the pallium and subpallium, diencephalon, mesencephalon and cerebellum. Generally, the olfactory bulbs and telencephalon had more PCNA and DCX cells than other regions. Two proliferative hotspots were evident in the dorsal and ventral poles of the lateral ventricles. PCNA- and DCX-immunoreactive cells migrated radially from the walls of the lateral ventricle into the parenchyma. In most telencephalic regions, the density of PCNA- and DCX-immunoreactive cells increased from rostral to caudal, except in the mesopallium where the density decreased from rostral to middle levels and then increased caudally. DCX immunoreactivity was more intense in fibres than in cell bodies and DCX-immunoreactive cells included small granular cells, fusiform bipolar cells, large round and or polygonal multipolar cells. The similarity in the distribution of proliferating cells and new neurons in the telencephalon of the two breeds of pigeons may suggest that adult neurogenesis is a conserved trait as an ecological adaptation irrespective of body size.

Toxic effects of prolonged administration of leaves of cassava (Manihot esculenta Crantz) to goats.

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Soto-Blanco, Benito; Górniak, Silvana Lima

2010-07-01

Cassava (Manihot esculenta Crantz) is a major source of dietary energy for humans and domestic animals in many tropical countries. However, consumption of cassava is limited by its characteristic content of cyanogenic glycosides. The present work aimed to evaluate the toxic effects of ingestion of cassava leaves by goats for 30 consecutive days, and to compare the results with the toxic effects of cyanide in goats, which have been described previously. Eight Alpine cross-bred female goats were divided into two equal groups, and were treated with ground frozen cassava leaves at a target dose of 6.0mg hydrogen cyanide (HCN)/kg/day (treated animals), or with ground hay and water only (control group) by gavage for 30 consecutive days. Blood samples were collected on days 0, 7, 15, 21, and 30 for biochemical panel and cyanide determination. At the end of the experiment, fragments of pancreas, thyroid gland, liver, kidney, lungs, heart, spleen, and the whole central nervous system were collected for histopathological examination. Clinical signs were observed in all goats treated with cassava on the first day of the experiment. From the second day the dose of cassava leaves was reduced to 4.5mgHCN/kg/day. No changes were found in the blood chemical panel. A mild increase in the number of resorption vacuoles in the thyroid follicular colloid, slight vacuolation of periportal hepatocytes, and spongiosis of the mesencephalon were found in goats treated with cassava. The pattern of lesions seen in the present goats was similar to what has been described previously in cyanide-dosed goats. Thus, the toxic effects of the ingestion of cassava leaves by goats can be attributed to the action of cyanide released from cyanogenic glycosides, and none of the effects was promoted by these glycosides directly.

Magnetic Resonance Imaging of a Case of Central Neurocytoma

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Dedushi, Kreshnike; Kabashi, Serbeze; Ugurel, Mehmet Sahin; Ramadani, Naser; Mucaj, Sefedin; Zeqiraj, Kamber

2016-01-01

Background: The purpose of this study is to investigate the MRI features of central neurocytoma. Case report: A 45 year old man with 3 months of worsening daily headaches. These headaches were diffuse, lasted for several hours, and mostly occurred in the morning. She was initially diagnosed and treated for migraines but later he had epileptic attack and diplopia and neurolog recomaded MRI. Methods: precontrast MRI; TSE/T2Wsequence in axial/coronal planes; 3D–Hi-resolution T1W sagittal; FLAIR/T2W axial; FLAIR/T2W and Flash/T2W oblique coronal plane (perpendicular to temporal lobes) GRE/T2W axial plane for detection of heme products. Post-contrast TSE/T1W sequence in axial, coronal and sagittal planes. Diffusion weighted and ADC mapping MRI images for EPI sequence in axial plane. Results: A 23x12mm heterogeneous mass within aqueductus cerebri, with calcified and hemorrhagic foci and extending downwards till fourth ventricle. It’s originating from the right paramedian posterior aqueductal wall (tectum), and also extending to and involving the tegmentum of mesencephalon at its right paramedian aspect. CSF flow obstruction secondary to described aqueductal mass, with resultant triventricular hydrocephalus). Marked transependymal CSF leak can be noted at periventricular white matter, secondary to severe hydrocephalus. After IV injection of contrast media, this mass shows mild-to-moderate heterogenous speckled enhancement. Conclusion: MRI is helpful in defining tumor extension, which is important in preoperative planning. Although IN is a relatively rare lesion, it should be considered in the differential diagnosis of intraventricular lesions in the presence of such typical MR findings. However, a definitive diagnosis requires immunochemical study and electron microscopy. PMID:28077908

Developmental disturbances of the fetal brain in guinea-pigs caused by methylmercury

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Inouye, Minoru; Kajiwara, Yuji

1988-08-01

Pregnant guinea-pigs of Hartley strain were orally administered methylmercuric chloride once at a dose of 7.5 mg Hg/animal (weighing 500-800 g) on one of days 21, 28, 35, 42 or 49 (3-7 weeks) of gestation. They were killed on day 63 (9 weeks) and their fetuses were removed. Both maternal and fetal blood, brain, liver and kidney, and fetal hair, urine, gastric content and amniotic fluid as well, were sampled for mercury analysis. The fetal brains were also examined pathologically. The maternal kidney contained mercury at a high concentration but the fetal kidney did not. The mercury concentration was strikingly high in the fetal hair, but fairly low in the urine, gastric contents and amniotic fluid. Mercury distributed unevenly in various brain regions of both dams and fetuses after treatment at 6 and 7 weeks of pregnancy (3 and 2 weeks before sampling). The concentration was high in the neopallium and archipallium, followed by the paleopallium, diencephalon and mesencephalon, but low in the rhombencephalon, including cerebellum. Mercury contents were relatively low and distributed almost evenly in various brain regions of both the dams and fetuses following treatment at 3, 4 and 5 weeks of pregnancy. Morphologically, the fetal brains were disturbed in the development following treatment at 3, 4 and 5 weeks of pregnancy. The cerebral cortex was thinned, the nucleus caudatus putamen and the hippocampal formation were reduced in size, and the lateral ventricles were dilated. However, the histological architecture of the cerebral cortex was not strikingly maldeveloped; only a slight disarrangement of the cellular alignment was noted. Following treatment at 6 and 7 weeks of pregnancy, focal degeneration of the neuronal cells was observed in the fetal neocortex; the severe cases showed spongy degeneration and dysgenetic hydrocephalus.

Oestrogen influences on mitochondrial gene expression and respiratory chain activity in cortical and mesencephalic astrocytes.

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Araújo, G W; Beyer, C; Arnold, S

2008-07-01

The regulation of mitochondrial energy metabolism plays an essential role in the central nervous system (CNS). Abnormalities of the mitochondrial respiratory chain often accompany neurodegenerative diseases. This makes mitochondria a perfect target for strategies of cellular protection against toxic compounds and pathological conditions. Steroid hormones, such as oestrogen, are well-known to fulfil a protective role in the brain during ischaemic and degenerative processes. Because astrocytes function as the major energy supplier in the CNS, we have analysed oestrogen effects on the mitochondrial respiratory chain of this cell type. In our studies, we applied semi- and quantitative polymerase chain reaction analysis of gene expression and polarographic measurements of the respiratory chain activity of mitochondria. We observed that structural and functional properties were regulated dependent on the oestrogen exposure time and the brain region, but independent of the nuclear oestrogen receptors. We could demonstrate that long-term oestrogen exposure increases the subunit gene expression of respiratory chain complexes and the mitochondrial DNA content, thereby indicating an up-regulation of the amount of mitochondria per cell together with an increase of mitochondrial energy production. This could represent an important indirect mechanism by which long-term oestrogen exposure protects neurones from cell death under neurotoxic conditions. On the other hand, we observed short-term effects of oestrogen on the activity of mitochondrial, proton-pumping respiratory chain complexes. In astrocytes from the cortex, respiratory chain activity was decreased, whereas it was increased in astrocytes from the mesencephalon. An increased production of reactive oxygen species would be the consequence of an increased respiratory chain activity in mesencephalic astrocytes. This could explain the different efficiencies of oestrogen-mediated short-term protection in distinct brain

Cerebral metabonomics study on Parkinson's disease mice treated with extract of Acanthopanax senticosus harms.

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Li, Xu-zhao; Zhang, Shuai-nan; Lu, Fang; Liu, Chang-feng; Wang, Yu; Bai, Yu; Wang, Na; Liu, Shu-min

2013-10-15

Extract of Acanthopanax senticosus harms (EAS) has neuroprotective effect on Parkinson's disease (PD) mice against dopaminergic neuronal damage. However, studies of its anti-PD mechanism are challenging, owing to the complex pathophysiology of PD, and complexity of EAS with multiple constituents acting on different metabolic pathways. Here, we have investigated the metabolic profiles and potential biomarkers in a mice model of MPTP-induced PD after treatment of EAS. Metabonomics based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used to profile the metabolic fingerprints of mesencephalon obtained from 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine Hydrochloride (MPTP-HCl)-induced PD mice model with and without EAS treatment. Through partial least squares-discriminate analysis (PLS-DA), it was observed that metabolic perturbations induced by MPTP were restored after treatment with EAS. Metabolites with significant changes induced by MPTP, including L-dopa, 5'-methylthioadenosine, tetradecanoylcarnitine, phytosphingosine-1-P, Cer(d18:0/18:0), LysoPC(20:4(5Z,8Z,11Z,14Z)), L-palmitoyl -carnitine, tetracosanoylglycine, morphiceptin and stearoylcarnitine, were characterized as potential biomarkers involved in the pathogenesis of PD. The derivations of all those biomarkers can be regulated by EAS treatment except Cer(d18:0/18:0), LysoPC(20:4(5Z,8Z,11Z,14Z)), morphiceptin. The therapeutic effect of EAS on PD may involve in regulating the tyrosine metabolism, mitochondrial beta-oxidation of long chain saturated fatty acids, fatty acid metabolism, methionine metabolism, and sphingolipid metabolism. This study indicated that changed metabolites can be certainly recovered by EAS, and the treatment of EAS can be connected with the regulation of related metabolic pathways. Copyright © 2013 Elsevier GmbH. All rights reserved.

The cytoarchitecture of the torus semicircularis in the Tegu lizard, Tupinambis nigropunctatus.

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Browner, R H; Rubinson, K

1977-12-15

The torus semicircularis (TS) of the Tegu lizard extends from the superficial caudal mesencephalon, dorsal to the exiting trochlear nerve, to a position ventral to the middle part of the optic tectum and its ventricle. It has an oblique orientation with the caudal pole abutting the midline while the rostal end is lateral and slightly ventral. The TS consists of a central nucleus and several adjacent cell groups. The central nucleus and the laminar nucleus, situated medially, extend the entire length of the TS while the cortical nucleus, situated dorsally and laterally, is present only in the caudal superficial portion. The central nucleus is composed of ovoid neurons with branched, radiating dendrites. The dendrites are directed medially and laterally with spines on the distal portion of the dendritic tree. The laminar nucleus consists of three to five neuronal layers. It is mainly composed of fusiform neurons with one dendritic trunk from each extremity of the soma. There is little branching and few dendritic spines. The cortical nucleus is a laminated region consisting of alternating layers of neurons and lateral lemniscal fibers. The neurons of the superficial layers are fusiform with their long axis perpendicular to the long axis of the brainstem. They possess two main dendritic trunks which parallel the laminae and are covered with dendritic spines. The deeper layers consist of pyramidal neurons with three dendritic trunks, secondary branches, and few spines. The long axis of these neurons extends from the center of the TS to the periphery. Two dendritic trunks extend dorsally or laterally towards the surface, while the third extends towards the central nucleus. The dendrites, thus, extend across the laminae. In addition, a cell-free lateral zone is described.

Postotic and preotic cranial neural crest cells differently contribute to thyroid development.

Science.gov (United States)

Maeda, Kazuhiro; Asai, Rieko; Maruyama, Kazuaki; Kurihara, Yukiko; Nakanishi, Toshio; Kurihara, Hiroki; Miyagawa-Tomita, Sachiko

2016-01-01

Thyroid development and formation vary among species, but in most species the thyroid morphogenesis consists of five stages: specification, budding, descent, bilobation and folliculogenesis. The detailed mechanisms of these stages have not been fully clarified. During early development, the cranial neural crest (CNC) contributes to the thyroid gland. The removal of the postotic CNC (corresponding to rhombomeres 6, 7 and 8, also known as the cardiac neural crest) results in abnormalities of the cardiovascular system, thymus, parathyroid glands, and thyroid gland. To investigate the influence of the CNC on thyroid bilobation process, we divided the CNC into two regions, the postotic CNC and the preotic CNC (from the mesencephalon to rhombomere 5) regions and examined. We found that preotic CNC-ablated embryos had a unilateral thyroid lobe, and confirmed the presence of a single lobe or the absence of lobes in postotic CNC-ablated chick embryos. The thyroid anlage in each region-ablated embryos was of a normal size at the descent stage, but at a later stage, the thyroid in preotic CNC-ablated embryos was of a normal size, conflicting with a previous report in which the thyroid was reduced in size in the postotic CNC-ablated embryos. The postotic CNC cells differentiated into connective tissues of the thyroid in quail-to-chick chimeras. In contrast, the preotic CNC cells did not differentiate into connective tissues of the thyroid. We found that preotic CNC cells encompassed the thyroid anlage from the specification stage to the descent stage. Finally, we found that endothelin-1 and endothelin type A receptor-knockout mice and bosentan (endothelin receptor antagonist)-treated chick embryos showed bilobation anomalies that included single-lobe formation. Therefore, not only the postotic CNC, but also the preotic CNC plays an important role in thyroid morphogenesis. Copyright © 2015 Elsevier Inc. All rights reserved.

Histological studies in developing brain after 0.5 Gy neutron irradiation in utero

International Nuclear Information System (INIS)

Antal, S.; Fueloep, Z.

1986-01-01

Pregnant mice were irradiated with 0.5 Gy neutrons on day 13, 15 or 18 of gestation. There was no significant difference in number of living young born per litter between in neutron irradiated mice and controls. Mortality of irradiated offspings increased in the first 3 days after birth. The brain weight of 21-day old animals after neutron irradiation averaged only 55, 56 and 69% of controls, resp. At six hours after irradiation morphological analysis showed nuclear pyknosis in the central nervous system. On day 13 the telencephalon was severely affected. The 30% cells were pyknotic in the wall of the cerebral hemisphere and 20% of cells in corpus striatum. In the metencephalon marked pyknosis was established in the tectal lamina of mesencephalon (16%) and in the cerebellar anlage (21%). The olfactory plate (24%), the ventricular zone of cerebral hemisphere (30%) and colliculus ganglionaris were damaged mostly (40%) after radiation on day 15 of gestation. The tectum of the mesencephali and in metencephalon the external granular layer of cerebellum and area of the rhombic lip were affected by irradiation (17-20%). The telencephalon found pyknotic but to a less extent in group irradiated on day 18 than it was on day 15. In the olfactory bulb 10% of pyknotic cells were seen and 16% of primary cortex of cerebral hemisphere more over 30% of nucleus caudatus/putamen were affected. In metencephalon 19% of external granular layer of cerebellum and 13% of trigonum cerebelli were pyknotic. In general, lesions of irradiation were rather mild in diencephalon and myelencephalon at all examined ages. Histological examinations support that defined parts of brain are damaged after neutron irradiation in utero and it may lead to the described physiological 18-20 and biochemical consequences 20,23 . (orig.)

The Ontogeny and Brain Distribution Dynamics of the Appetite Regulators NPY, CART and pOX in Larval Atlantic Cod (Gadus morhua L.).

Science.gov (United States)

Le, Hoang T M D; Angotzi, Anna Rita; Ebbesson, Lars O E; Karlsen, Ørjan; Rønnestad, Ivar

2016-01-01

Similar to many marine teleost species, Atlantic cod undergo remarkable physiological changes during the early life stages with concurrent and profound changes in feeding biology and ecology. In contrast to the digestive system, very little is known about the ontogeny and the localization of the centers that control appetite and feed ingestion in the developing brain of fish. We examined the expression patterns of three appetite regulating factors (orexigenic: neuropeptide Y, NPY; prepro-orexin, pOX and anorexigenic: cocaine- and amphetamine-regulated transcript, CART) in discrete brain regions of developing Atlantic cod using chromogenic and double fluorescent in situ hybridization. Differential temporal and spatial expression patterns for each appetite regulator were found from first feeding (4 days post hatch; dph) to juvenile stage (76 dph). Neurons expressing NPY mRNA were detected in the telencephalon (highest expression), diencephalon, and optic tectum from 4 dph onward. CART mRNA expression had a wider distribution along the anterior-posterior brain axis, including both telencephalon and diencephalon from 4 dph. From 46 dph, CART transcripts were also detected in the olfactory bulb, region of the nucleus of medial longitudinal fascicle, optic tectum and midbrain tegmentum. At 4 and 20 dph, pOX mRNA expression was exclusively found in the preoptic region, but extended to the hypothalamus at 46 and 76 dph. Co-expression of both CART and pOX genes were also observed in several hypothalamic neurons throughout larval development. Our results show that both orexigenic and anorexigenic factors are present in the telencephalon, diencephalon and mesencephalon in cod larvae. The telencephalon mostly contains key factors of hunger control (NPY), while the diencephalon, and particularly the hypothalamus may have a more complex role in modulating the multifunctional control of appetite in this species. As the larvae develop, the overall progression in temporal and

A discrete dopaminergic projection from the incertohypothalamic A13 cell group to the dorsolateral periaqueductal gray in rat

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Fany eMessanvi

2013-12-01

Full Text Available Several findings have indicated an involvement of dopamine in panic and defensive behaviors. The dorsolateral column of the periaqueductal gray (dlPAG is crucially involved in the expression of panic attacks in humans and defensive behaviors, also referred to as panic-like behaviors, in animals. Although the dlPAG is known to receive a specific innervation of dopaminergic fibers and abundantly expresses dopamine receptors, the origin of this dopaminergic input is largely unknown. This study aimed at mapping the dopaminergic projections to the dlPAG in order to provide further insight into the panic-like related behavior circuitry of the dlPAG. For this purpose, the retrograde tracer cholera toxin subunit b (CTb was injected into the dlPAG of male Wistar rats and double immunofluorescence for CTb and tyrosine hydroxylase (TH, the rate-limiting enzyme in the synthesis of dopamine, was performed. Neurons labeled for both CTb and TH were counted in different dopaminergic cell groups. The findings indicate that the dopaminergic nerve terminals present in the dlPAG originate from multiple dopamine-containing cell groups in the hypothalamus and mesencephalon. Interestingly, the A13 cell group is the main source of dopaminergic afferents to the dlPAG and contains at least 45% of the total number of CTb/TH-positive neurons. Anterograde tracing with biotinylated dextran amine (BDA combined with double immunofluorescence for BDA and TH confirmed the projections from the A13 cell group to the dlPAG. The remainder of the dopamine-positive terminals present in the dlPAG was found to originate from the extended A10 cell group and the A11 group. The A13 cell group is known to send dopaminergic efferents to several other brain regions implicated in defensive behavior, including the central amygdala and ventromedial hypothalamus. Therefore, although direct behavioral evidence is lacking, our finding that the A13 cell group is also the main source of dopaminergic

Suppression of bulboreticular unit responses to noxious stimuli by analgesic mesencephalic stimulation.

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Morrow, T J; Casey, K L

1983-01-01

The responses of 302 neurons in the medial medullary reticular formation (MRF) to a variety of noxious and innocuous somatic stimuli were studied in anesthetized and awake rats. In addition, the effects of analgesic electrical stimulation in the mesencephalon (MES) on unit responses were examined. Tail shock was the most effective stimulus, exciting more than 80% of all units recorded. This stimulus was considered separately during data analysis, since it could not be classified as noxious or innocuous. Noxious somatic stimuli (including pinch, firm pressure, pin prick, and radiant heating of the tail above 45 degrees C were especially effective in eliciting discharge in a significant fraction of all cells in both awake (123/205) and anesthetized (45/97) animals. Nociceptive neurons could be classified as nociceptive specific (NS) or wide dynamic range (WDR) depending on their responses to all somatic stimuli tested. Nociceptive neurons showed no preferential anatomical distribution. Most neurons, including those responsive to noxious inputs, exhibited large, often bilateral receptive fields which frequently covered the tail, one or more limbs, and extensive areas of the body or head. Electrical stimulation within or adjacent to the mesencephalic periaqueductal gray matter depressed the spontaneous and evoked discharge of MRF neurons in both acute and chronic preparations. This inhibition showed a significant preference (p less than 0.001, chi-square statistic) for units that were excited by somatic and especially noxious stimuli. No units were facilitated by MES stimulation. In the awake rat, unit suppression closely followed the time course and level of MES-induced analgesia. Excitability data from the acute experiments suggest that this response inhibition may be the result of a direct action on MRF neurons. Anesthesia severely depressed the spontaneous discharge of MRF neurons as well as the activity evoked by innocuous somatic stimulation. Our data suggest

Proliferation zones in the axolotl brain and regeneration of the telencephalon

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Maden Malcolm

2013-01-01

Full Text Available Abstract Background Although the brains of lower vertebrates are known to exhibit somewhat limited regeneration after incisional or stab wounds, the Urodele brain exhibits extensive regeneration after massive tissue removal. Discovering whether and how neural progenitor cells that reside in the ventricular zones of Urodeles proliferate to mediate tissue repair in response to injury may produce novel leads for regenerative strategies. Here we show that endogenous neural progenitor cells resident to the ventricular zone of Urodeles spontaneously proliferate, producing progeny that migrate throughout the telencephalon before terminally differentiating into neurons. These progenitor cells appear to be responsible for telencephalon regeneration after tissue removal and their activity may be up-regulated by injury through an olfactory cue. Results There is extensive proliferation of endogenous neural progenitor cells throughout the ventricular zone of the adult axolotl brain. The highest levels are observed in the telencephalon, especially the dorsolateral aspect, and cerebellum. Lower levels are observed in the mesencephalon and rhombencephalon. New cells produced in the ventricular zone migrate laterally, dorsally and ventrally into the surrounding neuronal layer. After migrating from the ventricular zone, the new cells primarily express markers of neuronal differentiative fates. Large-scale telencephalic tissue removal stimulates progenitor cell proliferation in the ventricular zone of the damaged region, followed by proliferation in the tissue that surrounds the healing edges of the wound until the telencephalon has completed regeneration. The proliferative stimulus appears to reside in the olfactory system, because telencephalic regeneration does not occur in the brains of olfactory bulbectomized animals in which the damaged neural tissue simply heals over. Conclusion There is a continual generation of neuronal cells from neural progenitor cells

Hypoxia Stress Modifies Na/K-ATPase, H/K-ATPase, , and Isoform Expression in the Brain of Immune-Challenged Air-Breathing Fish

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MC Subhash Peter

2017-11-01

Full Text Available Fishes are equipped to sense stressful stimuli and are able to respond to environmental stressor such as hypoxia with varying pattern of stress response. The functional attributes of brain to hypoxia stress in relation to ion transport and its interaction during immune challenge have not yet delineated in fish. We, therefore, explored the pattern of ion transporter functions and messenger RNA (mRNA expression of α1-subunit isoforms of Na + /K + -ATPase (NKA in the brain segments, namely, prosencephalon (PC, mesencephalon (MC, and metencephalon (MeC in an obligate air-breathing fish exposed either to hypoxia stress (30 minutes forced immersion in water or challenged with zymosan treatment (25-200 ng g −1 for 24 hours or both. Zymosan that produced nonspecific immune responses evoked differential regulation of NKA, H + /K + -ATPase (HKA, and Na + / NH 4 + - ATPase (NNA in the varied brain segments. On the contrary, hypoxia stress that demanded activation of NKA in PC and MeC showed a reversed NKA activity pattern in MeC of immune-challenged fish. A compromised HKA and NNA regulation during hypoxia stress was found in immune-challenged fish, indicating the role of these brain ion transporters to hypoxia stress and immune challenges. The differential mRNA expression of α1-subunit isoforms of NKA, nkaα1a , nkaα1b , and nkaα1c , in hypoxia-stressed brain showed a shift in its expression pattern during hypoxia stress-immune interaction in PC and MC. Evidence is thus presented for the first time that ion transporters such as HKA and NNA along with NKA act as functional brain markers which respond differentially to both hypoxia stress and immune challenges. Taken together, the data further provide evidence for a differential Na + , K + , H + , and NH 4 + ion signaling that exists in brain neuronal clusters during hypoxia stress-immune interaction as a result of modified regulations of NKA, HKA, and NNA transporter functions and nkaα1 isoform

Hypoxia Stress Modifies Na+/K+-ATPase, H+/K+-ATPase, Na+/NH4+-ATPase, and nkaα1 Isoform Expression in the Brain of Immune-Challenged Air-Breathing Fish

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Peter, MC Subhash; Simi, Satheesan

2017-01-01

Fishes are equipped to sense stressful stimuli and are able to respond to environmental stressor such as hypoxia with varying pattern of stress response. The functional attributes of brain to hypoxia stress in relation to ion transport and its interaction during immune challenge have not yet delineated in fish. We, therefore, explored the pattern of ion transporter functions and messenger RNA (mRNA) expression of α1-subunit isoforms of Na+/K+-ATPase (NKA) in the brain segments, namely, prosencephalon (PC), mesencephalon (MC), and metencephalon (MeC) in an obligate air-breathing fish exposed either to hypoxia stress (30 minutes forced immersion in water) or challenged with zymosan treatment (25-200 ng g−1 for 24 hours) or both. Zymosan that produced nonspecific immune responses evoked differential regulation of NKA, H+/K+-ATPase (HKA), and Na+/NH4+-ATPase (NNA) in the varied brain segments. On the contrary, hypoxia stress that demanded activation of NKA in PC and MeC showed a reversed NKA activity pattern in MeC of immune-challenged fish. A compromised HKA and NNA regulation during hypoxia stress was found in immune-challenged fish, indicating the role of these brain ion transporters to hypoxia stress and immune challenges. The differential mRNA expression of α1-subunit isoforms of NKA, nkaα1a, nkaα1b, and nkaα1c, in hypoxia-stressed brain showed a shift in its expression pattern during hypoxia stress-immune interaction in PC and MC. Evidence is thus presented for the first time that ion transporters such as HKA and NNA along with NKA act as functional brain markers which respond differentially to both hypoxia stress and immune challenges. Taken together, the data further provide evidence for a differential Na+, K+, H+, and NH4+ ion signaling that exists in brain neuronal clusters during hypoxia stress-immune interaction as a result of modified regulations of NKA, HKA, and NNA transporter functions and nkaα1 isoform regulation. PMID:29238219

Hypoxia Stress Modifies Na+/K+-ATPase, H+/K+-ATPase, [Formula: see text], and nkaα1 Isoform Expression in the Brain of Immune-Challenged Air-Breathing Fish.

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Peter, Mc Subhash; Simi, Satheesan

2017-01-01

Fishes are equipped to sense stressful stimuli and are able to respond to environmental stressor such as hypoxia with varying pattern of stress response. The functional attributes of brain to hypoxia stress in relation to ion transport and its interaction during immune challenge have not yet delineated in fish. We, therefore, explored the pattern of ion transporter functions and messenger RNA (mRNA) expression of α1-subunit isoforms of Na + /K + -ATPase (NKA) in the brain segments, namely, prosencephalon (PC), mesencephalon (MC), and metencephalon (MeC) in an obligate air-breathing fish exposed either to hypoxia stress (30 minutes forced immersion in water) or challenged with zymosan treatment (25-200 ng g -1 for 24 hours) or both. Zymosan that produced nonspecific immune responses evoked differential regulation of NKA, H + /K + -ATPase (HKA), and [Formula: see text] (NNA) in the varied brain segments. On the contrary, hypoxia stress that demanded activation of NKA in PC and MeC showed a reversed NKA activity pattern in MeC of immune-challenged fish. A compromised HKA and NNA regulation during hypoxia stress was found in immune-challenged fish, indicating the role of these brain ion transporters to hypoxia stress and immune challenges. The differential mRNA expression of α1-subunit isoforms of NKA, nkaα1a , nkaα1b , and nkaα1c , in hypoxia-stressed brain showed a shift in its expression pattern during hypoxia stress-immune interaction in PC and MC. Evidence is thus presented for the first time that ion transporters such as HKA and NNA along with NKA act as functional brain markers which respond differentially to both hypoxia stress and immune challenges. Taken together, the data further provide evidence for a differential Na + , K + , H + , and [Formula: see text] ion signaling that exists in brain neuronal clusters during hypoxia stress-immune interaction as a result of modified regulations of NKA, HKA, and NNA transporter functions and nkaα1 isoform

GFAP-immunopositive structures in spiny dogfish, Squalus acanthias, and little skate, Raia erinacea, brains: differences have evolutionary implications.

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Kálmán, M; Gould, R M

2001-07-01

GFAP expression patterns were compared between the brains of a spiny dogfish (Squalus acanthias) and a little skate (Raia erinacea). After anesthesia, the animals were perfused with paraformaldehyde. Serial vibratome sections were immunostained against GFAP using the avidin-biotin method. Spiny dogfish brain contained mainly uniformly-distributed, radially arranged ependymoglia. From GFAP distribution, the layered organization in both the telencephalon and the tectum were visible. In the cerebellum, the molecular and granular layers displayed conspicuously different glial structures; in the former a Bergmann glia-like population was found. No true astrocytes (i.e., stellate-shaped cells) were found. Radial glial endfeet lined all meningeal surfaces. Radial fibers also seemed to form endfeet and en passant contacts on the vessels. Plexuses of fine perivascular glial fibers also contributed to the perivascular glia. Compared with spiny dogfish brain, GFAP expression in the little skate brain was confined. Radial glia were limited to a few areas, e.g., segments of the ventricular surface of the telencephalon, and the midline of the diencephalon and mesencephalon. Scarce astrocytes occurred in every brain part, but only the optic chiasm, and the junction of the tegmentum and optic tectum contained large numbers of astrocytes. Astrocytes formed the meningeal glia limitans and the perivascular glia. No GFAP-immunopositive Bergmann glia-like structure was found. Astrocytes seen in the little skate were clearly different from the mammalian and avian ones; they had a different process system - extra large forms were frequently seen, and the meningeal and perivascular cells were spread along the surface instead of forming endfeet by processes. The differences between Squalus and Raia astroglia were much like those found between reptiles versus mammals and birds. It suggests independent and parallel glial evolutionary processes in amniotes and chondrichthyans, seemingly

Experimental and iatrogenic poisoning by sodium selenite in pigs

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Paulo V. Peixoto

Full Text Available ABSTRACT: Following a case of iatrogenic selenium poisoning in a young pig, an experimental study was carry out. Sodium selenite was orally and parenterally administered to 13 pigs that were subdivided into three groups (G1, G2 and G3. The animals in groups G1 and G3 received sodium selenite intramuscularly (IM, G1 received a comercial formula, and G3 received sodium selenite mixed with distilled water at different dosages, and those in group G2 were fed commercial sodium selenite. Acute and subacute poisoning was observed in both groups, although the onset of clinical signs was slower in group G2. Only one pig (in group G1 that had received the highest dose showed a peracute course. Apathy, anorexia, dyspnea, vomiting, muscular tremors, proprioceptive deficit, ataxia and paresis of the hind limbs progressing to the front limbs evolving to tetraplegia were observed. Postmortem findings differed whether the animals received the injected (G1 and G3 or oral (G2 sodium selenite. The liver was moderately atrophic in some animals of G2. Some of the animals in groups G1 and G3 presented with lung edema. One pig in G3 had yellowish-brown areas in the ventral horns of the cervical intumescences of the spinal cord. The most important histological changes were present in the ventral horns of the cervical and lumbar intumescences of the spinal cord. In one animal, changes were present in the brainstem and mesencephalon. The initial lesion was a perivascular and astrocyte edema that progressing to lysis and death of astrocytes and neurons. In the chronic stage of the lesions, there were extensive areas of liquefaction necrosis with perivascular lymphocytic and histiocytic infiltration and occasional eosinophils. It seems that disruption of the blood-brain barrier due to astrocyte edema is the most likely mechanism of CNS lesion.

Opposite modulation of brain stimulation reward by NMDA and AMPA receptors in the ventral tegmental area.

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Ducrot, Charles; Fortier, Emmanuel; Bouchard, Claude; Rompré, Pierre-Paul

2013-01-01

Previous studies have shown that blockade of ventral tegmental area (VTA) glutamate N-Methyl-D-Aspartate (NMDA) receptors induces reward, stimulates forward locomotion and enhances brain stimulation reward. Glutamate induces two types of excitatory response on VTA neurons, a fast and short lasting depolarization mediated by α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors and a longer lasting depolarization mediated by NMDA receptors. A role for the two glutamate receptors in modulation of VTA neuronal activity is evidenced by the functional change in AMPA and NMDA synaptic responses that result from repeated exposure to reward. Since both receptors contribute to the action of glutamate on VTA neuronal activity, we studied the effects of VTA AMPA and NMDA receptor blockade on reward induced by electrical brain stimulation. Experiments were performed on rats trained to self-administer electrical pulses in the medial posterior mesencephalon. Reward thresholds were measured with the curve-shift paradigm before and for 2 h after bilateral VTA microinjections of the AMPA antagonist, NBQX (2,3,-Dioxo-6-nitro-1,2,3,4-tetrahydrobenzo(f)quinoxaline-7-sulfonamide, 0, 80, and 800 pmol/0.5 μl/side) and of a single dose (0.825 nmol/0.5 μl/side) of the NMDA antagonist, PPPA (2R,4S)-4-(3-Phosphonopropyl)-2-piperidinecarboxylic acid). NBQX produced a dose-dependent increase in reward threshold with no significant change in maximum rate of responding. Whereas PPPA injected at the same VTA sites produced a significant time dependent decrease in reward threshold and increase in maximum rate of responding. We found a negative correlation between the magnitude of the attenuation effect of NBQX and the enhancement effect of PPPA; moreover, NBQX and PPPA were most effective when injected, respectively, into the anterior and posterior VTA. These results suggest that glutamate acts on different receptor sub-types, most likely located on different VTA neurons, to

Atomoxetine affects transcription/translation of the NMDA receptor and the norepinephrine transporter in the rat brain – an in vivo study

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Udvardi, Patrick T; Föhr, Karl J; Henes, Carolin; Liebau, Stefan; Dreyhaupt, Jens; Boeckers, Tobias M; Ludolph, Andrea G

2013-01-01

Attention-deficit/hyperactivity disorder (ADHD) is the most frequently diagnosed neurodevelopmental disorder. The norepinephrine transporter (NET) inhibitor atomoxetine, the first nonstimulant drug licensed for ADHD treatment, also acts as an N-methyl-D-aspartate receptor (NMDAR) antagonist. The compound’s effects on gene expression and protein levels of NET and NMDAR subunits (1, 2A, and 2B) are unknown. Therefore, adolescent Sprague Dawley rats were treated with atomoxetine (3 mg/kg, intraperitoneal injection [ip]) or saline (0.9%, ip) for 21 consecutive days on postnatal days (PND) 21–41. In humans, atomoxetine’s earliest clinical therapeutic effects emerge after 2–3 weeks. Material from prefrontal cortex, striatum (STR), mesencephalon (MES), and hippocampus (HC) was analyzed either directly after treatment (PND 42) or 2 months after termination of treatment (PND 101) to assess the compound’s long-term effects. In rat brains analyzed immediately after treatment, protein analysis exhibited decreased levels of the NET in HC, and NMDAR subunit 2B in both STR and HC; the transcript levels were unaltered. In rat brains probed 2 months after final atomoxetine exposure, messenger RNA analysis also revealed significantly reduced levels of genes coding for NMDAR subunits in MES and STR. NMDAR protein levels were reduced in STR and HC. Furthermore, the levels of two SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins, synaptophysin and synaptosomal-associated protein 25, were also significantly altered in both treatment groups. This in vivo study detected atomoxetine’s effects beyond NET inhibition. Taken together, these data reveal that atomoxetine seems to decrease glutamatergic transmission in a brain region-specific manner. Long-term data show that the compound’s impact is not due to an acute pharmacological effect but lasts or even amplifies after a drug-free period of 2 months, leading to altered development of

Opposite modulation of brain stimulation reward by NMDA and AMPA receptors in the ventral tegmental area.

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Charles eDucrot

2013-10-01

Full Text Available Previous studies have shown that blockade of ventral midbrain (VM glutamate N-Methyl-D-Aspartate (NMDA receptors induces reward, stimulates forward locomotion and enhances brain stimulation reward. Glutamate induces two types of excitatory response on VM neurons, a fast and short lasting depolarisation mediated by a-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA receptors and a longer lasting depolarization mediated by NMDA receptors. A role for the two glutamate receptors in modulation of VM neuronal activity is evidenced by the functional change in AMPA and NMDA synaptic responses that result from repeated exposure to reward. Since both receptors contribute to the action of glutamate on VM neuronal activity, we studied the effects of VM AMPA and NMDA receptor blockade on reward induced by electrical brain stimulation. Experiments were performed on rats trained to self-administer electrical pulses in the medial posterior mesencephalon. Reward thresholds were measured with the curve-shift paradigm before and for two hours after bilateral VM microinjections of the AMPA antagonist, NBQX (2,3,-Dioxo-6-nitro-1,2,3,4-tetrahydrobenzo(fquinoxaline-7-sulfonamide, 0, 80, and 800 pmol/0.5ul/side and of a single dose (0.825 nmol/0.5ul/side of the NMDA antagonist, PPPA (2R,4S-4-(3-Phosphonopropyl-2-piperidinecarboxylic acid. NBQX produced a dose-dependent increase in reward threshold with no significant change in maximum rate of responding. Whereas PPPA injected at the same VM sites produced a significant time dependent decrease in reward threshold and increase in maximum rate of responding. We found a negative correlation between the magnitude of the attenuation effect of NBQX and the enhancement effect of PPPA; moreover, NBQX and PPPA were most effective when injected respectively into the anterior and posterior VM. These results suggest that glutamate acts on different receptor sub-types, most likely located on different VM neurons, to modulate

Brain Magnetic Resonance Imaging of Siblings from Families with Two or More Children with Learning or Intellectual Disabilities and Need for Full-Time Special Education

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Mannerkoski, M.; Heiskala, H.; Aaberg, L. (Child Neurology, HUCH Dept. of Pediatric and Adolescent Medicine, Helsinki (Finland)); Raininko, R. (Dept. of Radiology, Uppsala Univ., Uppsala (Sweden)); Sarna, S. (Dept. of Public Health, Univ. of Helsinki, Helsinki (Finland)); Wirtavuori, K. (HUCH Dept. of Pediatric and Adolescent Medicine, Helsinki (Finland)); Autti, T. (HUCH Helsinki Medical Imaging Center, Helsinki (Finland))

2009-05-15

Background: Several factors are involved in determining a child's need for special education (Sweden). Thus, the value of brain magnetic resonance imaging (MRI) for subjects with learning and intellectual disabilities is uncertain. Purpose: To evaluate the usefulness of MRI in the diagnostic process of siblings with learning and intellectual disabilities and need for full-time SE. Material and Methods: Altogether, 119 siblings (mean age 11.9 years) from families in which two or more children attended/had previously attended full-time SE underwent prospective brain MRI. SE grouping included three levels, from specific learning disabilities (level 1) to global intellectual disabilities (level 3). Forty-three controls (level 0, mean age 12.0 years) attended mainstream education groups. Signal intensity and structural abnormalities were analyzed, and areas of the cerebrum, posterior fossa, corpus callosum, vermis and brain stem, and diameters of the corpus callosum were measured. In analyses, all area measurements were calculated in proportion to the total inner skull area. Results: Abnormal finding in MRI was more common for siblings (n=62; 52%) in SE (58% for level 3; 49% for level 2; 35% for level 1) than for controls (n=13; 16%). The siblings showed enlarged supra- (P<0.001) and infratentorial (P=0.015) cerebrospinal fluid (CSF) spaces and mild corpus callosum abnormalities (P=0.003) compared to controls. Siblings in SE had smaller inner skull area than controls (P<0.001). Further, the relative area of the mesencephalon (P=0.027) and the diameter of the body of the corpus callosum (P=0.015) were significantly smaller than in controls. In binary logistic regression analysis, enlarged supratentorial CSF spaces increased the probability of SE (odds ratio 4.2; P=0.023). Conclusion: Subjects with learning and intellectual disabilities commonly have more MRI findings than controls. Enlarged supratentorial CSF spaces were a frequent finding in siblings in full

FGF-2 deficiency does not influence FGF ligand and receptor expression during development of the nigrostriatal system.

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Ratzka, Andreas; Baron, Olga; Grothe, Claudia

2011-01-01

Secreted proteins of the fibroblast growth factor (FGF) family play important roles during development of various organ systems. A detailed knowledge of their temporal and spatial expression profiles, especially of closely related FGF family members, are essential to further identification of specific functions in distinct tissues. In the central nervous system dopaminergic neurons of the substantia nigra and their axonal projections into the striatum progressively degenerate in Parkinson's disease. In contrast, FGF-2 deficient mice display increased numbers of dopaminergic neurons. In this study, we determined the expression profiles of all 22 FGF-ligands and 10 FGF-receptor isoforms, in order to clarify, if FGF-2 deficiency leads to compensatory up-regulation of other FGFs in the nigrostriatal system. Three tissues, ventral mesencephalon (VM), striatum (STR) and as reference tissue spinal cord (SC) of wild-type and FGF-2 deficient mice at four developmental stages E14.5, P0, P28, and adult were comparatively analyzed by quantitative RT-PCR. As no differences between the genotypes were observed, a compensatory up-regulation can be excluded. Moreover, this analysis revealed that the majority of FGF-ligands (18/22) and FGF-receptors (9/10) are expressed during normal development of the nigrostriatal system and identified dynamic changes for some family members. By comparing relative expression level changes to SC reference tissue, general alterations in all 3 tissues, such as increased expression of FGF-1, -2, -22, FgfR-2c, -3c and decreased expression of FGF-13 during postnatal development were identified. Further, specific changes affecting only one tissue, such as increased FGF-16 (STR) or decreased FGF-17 (VM) expression, or two tissues, such as decreased expression of FGF-8 (VM, STR) and FGF-15 (SC, VM) were found. Moreover, 3 developmentally down-regulated FGFs (FGF-8b, FGF-15, FGF-17a) were functionally characterized by plasmid-based over-expression in

Cranial Neuropathy in Multiple Sclerosis

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Mine Hayriye Sorgun

2011-09-01

Full Text Available OBJECTIVE: It has been reported that cranial neuropathy findings could be seen in the neurologic examination of multiple sclerosis (MS patients, although brain magnetic resonance imaging (MRI may not reveal any lesion responsible for the cranial nerve involvement. The aim of this study was to determine the frequency of brainstem and cranial nerve involvement, except for olfactory and optic nerves, during MS attacks, and to investigate the rate of an available explanation for the cranial neuropathy findings by lesion localization on brain MRI. METHODS: Ninety-five attacks of 86 MS patients were included in the study. The patients underwent a complete neurological examination, and cranial nerve palsies (CNP were determined during MS attacks. RESULTS: CNP were found as follows: 3rd CNP in 7 (7.4%, 4th CNP in 1 (1.1%, 5th CNP in 6 (6.3%, 6th CNP in 12 (12.6%, 7th CNP in 5 (5.3%, 8th CNP in 4 (4.2%, and 9th and 10th CNP in 2 (2.1% out of 95 attacks. Internuclear ophthalmoplegia (INO was detected in 5 (5.4%, nystagmus in 37 (38.9%, vertigo in 9 (6.3%, and diplopia in 14 (14.7% out of 95 attacks. Pons, mesencephalon and bulbus lesions were detected in 58.7%, 41.5% and 21.1% of the patients, respectively, on the brain MRI. Cranial nerve palsy findings could not be explained by the localization of the lesions on brainstem MRI in 5 attacks; 2 of them were 3rd CNP (1 with INO, 2 were 6th CNP and 1 was a combination of 6th, 7th and 8th CNP. CONCLUSION: The most frequently affected cranial nerve and brainstem region in MS patients is the 6th cranial nerve and pons, respectively. A few of the MS patients have normal brainstem MRI, although they have cranial neuropathy findings in the neurologic examination.

Brain Magnetic Resonance Imaging of Siblings from Families with Two or More Children with Learning or Intellectual Disabilities and Need for Full-Time Special Education

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Mannerkoski, M.; Heiskala, H.; Aaberg, L.; Raininko, R.; Sarna, S.; Wirtavuori, K.; Autti, T.

2009-01-01

Background: Several factors are involved in determining a child's need for special education (SE). Thus, the value of brain magnetic resonance imaging (MRI) for subjects with learning and intellectual disabilities is uncertain. Purpose: To evaluate the usefulness of MRI in the diagnostic process of siblings with learning and intellectual disabilities and need for full-time SE. Material and Methods: Altogether, 119 siblings (mean age 11.9 years) from families in which two or more children attended/had previously attended full-time SE underwent prospective brain MRI. SE grouping included three levels, from specific learning disabilities (level 1) to global intellectual disabilities (level 3). Forty-three controls (level 0, mean age 12.0 years) attended mainstream education groups. Signal intensity and structural abnormalities were analyzed, and areas of the cerebrum, posterior fossa, corpus callosum, vermis and brain stem, and diameters of the corpus callosum were measured. In analyses, all area measurements were calculated in proportion to the total inner skull area. Results: Abnormal finding in MRI was more common for siblings (n=62; 52%) in SE (58% for level 3; 49% for level 2; 35% for level 1) than for controls (n=13; 16%). The siblings showed enlarged supra- (P<0.001) and infratentorial (P=0.015) cerebrospinal fluid (CSF) spaces and mild corpus callosum abnormalities (P=0.003) compared to controls. Siblings in SE had smaller inner skull area than controls (P<0.001). Further, the relative area of the mesencephalon (P=0.027) and the diameter of the body of the corpus callosum (P=0.015) were significantly smaller than in controls. In binary logistic regression analysis, enlarged supratentorial CSF spaces increased the probability of SE (odds ratio 4.2; P=0.023). Conclusion: Subjects with learning and intellectual disabilities commonly have more MRI findings than controls. Enlarged supratentorial CSF spaces were a frequent finding in siblings in full-time SE

Neuroprotective effects of edaravone-administration on 6-OHDA-treated dopaminergic neurons

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Wang Feifei

2008-08-01

Full Text Available Abstract Background Parkinson's disease (PD is a neurological disorder characterized by the degeneration of nigrostriatal dopaminergic systems. Free radicals induced by oxidative stress are involved in the mechanisms of cell death in PD. This study clarifies the neuroprotective effects of edaravone (MCI-186, 3-methyl-1-phenyl-2-pyrazolin-5-one, which has already been used for the treatment of cerebral ischemia in Japan, on TH-positive dopaminergic neurons using PD model both in vitro and in vivo. 6-hydroxydopamine (6-OHDA, a neurotoxin for dopaminergic neurons, was added to cultured dopaminergic neurons derived from murine embryonal ventral mesencephalon with subsequet administration of edaravone or saline. The number of surviving TH-positive neurons and the degree of cell damage induced by free radicals were analyzed. In parallel, edaravone or saline was intravenously administered for PD model of rats receiving intrastriatal 6-OHDA lesion with subsequent behavioral and histological analyses. Results In vitro study showed that edaravone significantly ameliorated the survival of TH-positive neurons in a dose-responsive manner. The number of apoptotic cells and HEt-positive cells significantly decreased, thus indicating that the neuroprotective effects of edaravone might be mediated by anti-apoptotic effects through the suppression of free radicals by edaravone. In vivo study demonstrated that edaravone-administration at 30 minutes after 6-OHDA lesion reduced the number of amphetamine-induced rotations significantly than edaravone-administration at 24 hours. Tyrosine hydroxylase (TH staining of the striatum and substantia nigra pars compacta revealed that edaravone might exert neuroprotective effects on nigrostriatal dopaminergic systems. The neuroprotective effects were prominent when edaravone was administered early and in high concentration. TUNEL, HEt and Iba-1 staining in vivo might demonstrate the involvement of anti-apoptotic, anti

Glioblastoma pediátrico: estudo clínico patológico de 12 casos com imunoistoquímica para proteína p53 Pediatric glioblastoma: a clinicopathological study of 12 cases with p53 protein immunohistochemistry

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Leonora Zozula Blind Pope

2007-12-01

Full Text Available Glioblastoma é um dos tumores primários mais letais do sistema nervoso central (SNC. Apesar dos significativos progressos, há poucas análises em crianças. Com o objetivo de avaliar localização, idade, sexo, sobrevida e imunoistoquímica para proteína p53, foram coletados casos de glioblastomas pediátricos do "Banco de Tumores do SNC de Curitiba", durante 1987-2003 e do Hospital Municipal Jesus, Rio de Janeiro, de 1970 a 1988. Doze preencheram os critérios de inclusão. A idade variou até 12 anos (média 7, sendo sete do sexo feminino e cinco do masculino. A sobrevida média foi 7,9 meses. Localizavam-se em hemisférios cerebrais (58,4%, mesencéfalo e tronco (33,3% e um no cerebelo. A imunoistoquímica demonstrou p53 positivo em 9 (75%. Em conclusão, glioblastoma tem comportamento semelhante entre crianças e adultos, sendo nestas menos freqüentes. Acomete hemisférios cerebrais com maior freqüência que estruturas infratentoriais, mostrando alta sensitividade com a imunomarcação para proteína p53, sendo nestes casos mais agressivos, com menor sobrevida.Glioblastoma is one of the most lethal central nervous system (CNS primary tumor. Although significant progress, only few analysis have been made in pediatric glioblastoma, which are less common and have worse prognosis than in adults. To evaluate gender, site, age, survival, and immunohistochemistry to p53, we selected cases of pediatric glioblastoma of "CNS Tumors Database in Curitiba", 1987-2003 and of the Hospital Municipal Jesus, Rio de Janeiro, 1970-1988. Twelve tumors were included. The age ranged from up to 12 years (median 7. There were 7 females and 5 males. The median survival was 7.9 months. Location was: cerebral hemispheres (58.4%, mesencephalon and brainstem (33.3% and one case in the cerebellum. Immunostained to p53 in 9 (75% cases. In conclusion, glioblastoma behaves similarly in children and adults. It is rare in children, affects both cerebral hemispheres more

Cathepsin K deficiency in mice induces structural and metabolic changes in the central nervous system that are associated with learning and memory deficits

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Oswald Julia

2011-07-01

Full Text Available Abstract Background Cathepsin K is a cysteine peptidase known for its importance in osteoclast-mediated bone resorption. Inhibitors of cathepsin K are in clinical trials for treatment of osteoporosis. However, side effects of first generation inhibitors included altered levels of related cathepsins in peripheral organs and in the central nervous system (CNS. Cathepsin K has been recently detected in brain parenchyma and it has been linked to neurobehavioral disorders such as schizophrenia. Thus, the study of the functions that cathepsin K fulfils in the brain becomes highly relevant. Results Cathepsin K messenger RNA was detectable in all brain regions of wild type (WT mice. At the protein level, cathepsin K was detected by immunofluorescence microscopy in vesicles of neuronal and non-neuronal cells throughout the mouse brain. The hippocampus of WT mice exhibited the highest levels of cathepsin K activity in fluorogenic assays, while the cortex, striatum, and cerebellum revealed significantly lower enzymatic activities. At the molecular level, the proteolytic network of cysteine cathepsins was disrupted in the brain of cathepsin K-deficient (Ctsk-/- animals. Specifically, cathepsin B and L protein and activity levels were altered, whereas cathepsin D remained largely unaffected. Cystatin C, an endogenous inhibitor of cysteine cathepsins, was elevated in the striatum and hippocampus, pointing to regional differences in the tissue response to Ctsk ablation. Decreased levels of astrocytic glial fibrillary acidic protein, fewer and less ramified profiles of astrocyte processes, differentially altered levels of oligodendrocytic cyclic nucleotide phosphodiesterase, as well as alterations in the patterning of neuronal cell layers were observed in the hippocampus of Ctsk-/- mice. A number of molecular and cellular changes were detected in other brain regions, including the cortex, striatum/mesencephalon, and cerebellum. Moreover, an overall induction of

The Ontogeny and Brain Distribution Dynamics of the Appetite Regulators NPY, CART and pOX in Larval Atlantic Cod (Gadus morhua L..

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Hoang T M D Le

Full Text Available Similar to many marine teleost species, Atlantic cod undergo remarkable physiological changes during the early life stages with concurrent and profound changes in feeding biology and ecology. In contrast to the digestive system, very little is known about the ontogeny and the localization of the centers that control appetite and feed ingestion in the developing brain of fish. We examined the expression patterns of three appetite regulating factors (orexigenic: neuropeptide Y, NPY; prepro-orexin, pOX and anorexigenic: cocaine- and amphetamine-regulated transcript, CART in discrete brain regions of developing Atlantic cod using chromogenic and double fluorescent in situ hybridization. Differential temporal and spatial expression patterns for each appetite regulator were found from first feeding (4 days post hatch; dph to juvenile stage (76 dph. Neurons expressing NPY mRNA were detected in the telencephalon (highest expression, diencephalon, and optic tectum from 4 dph onward. CART mRNA expression had a wider distribution along the anterior-posterior brain axis, including both telencephalon and diencephalon from 4 dph. From 46 dph, CART transcripts were also detected in the olfactory bulb, region of the nucleus of medial longitudinal fascicle, optic tectum and midbrain tegmentum. At 4 and 20 dph, pOX mRNA expression was exclusively found in the preoptic region, but extended to the hypothalamus at 46 and 76 dph. Co-expression of both CART and pOX genes were also observed in several hypothalamic neurons throughout larval development. Our results show that both orexigenic and anorexigenic factors are present in the telencephalon, diencephalon and mesencephalon in cod larvae. The telencephalon mostly contains key factors of hunger control (NPY, while the diencephalon, and particularly the hypothalamus may have a more complex role in modulating the multifunctional control of appetite in this species. As the larvae develop, the overall progression in

The Histamine H1 Receptor Participates in the Increased Dorsal Telencephalic Neurogenesis in Embryos from Diabetic Rats

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Karina H. Solís

2017-12-01

Full Text Available Increased neuron telencephalic differentiation during deep cortical layer formation has been reported in embryos from diabetic mice. Transitory histaminergic neurons within the mesencephalon/rhombencephalon are responsible for fetal histamine synthesis during development, fibers from this system arrives to the frontal and parietal cortex at embryo day (E 15. Histamine is a neurogenic factor for cortical neural stem cells in vitro through H1 receptor (H1R which is highly expressed during corticogenesis in rats and mice. Furthermore, in utero administration of an H1R antagonist, chlorpheniramine, decreases the neuron markers microtubuline associated protein 2 (MAP2 and forkhead box protein 2. Interestingly, in the diabetic mouse model of diabetes induced with streptozotocin, an increase in fetal neurogenesis in terms of MAP2 expression in the telencephalon is reported at E11.5. Because of the reported effects on cortical neuron differentiation of maternal diabetes in one hand and of histamine in the other, here the participation of histamine and H1R on the increased dorsal telencephalic neurogenesis was explored. First, the increased neurogenesis in the dorsal telencephalon at E14 in diabetic rats was corroborated by immunohistochemistry and Western blot. Then, changes during corticogenesis in the level of histamine was analyzed by ELISA and in H1R expression by qRT-PCR and Western blot and, finally, we tested H1R participation in the increased dorsal telencephalic neurogenesis by the systemic administration of chlorpheniramine. Our results showed a significant increase of histamine at E14 and in the expression of the receptor at E12. The administration of chlorpheniramine to diabetic rats at E12 prevented the increased expression of βIII-tubulin and MAP2 mRNAs (neuron markers and partially reverted the increased level of MAP2 protein at E14, concluding that H1R have an important role in the increased neurogenesis within the dorsal telencephalon

Functional and ultrastructural neuroanatomy of interactive intratectal/tectonigral mesencephalic opioid inhibitory links and nigrotectal GABAergic pathways: involvement of GABAA and mu1-opioid receptors in the modulation of panic-like reactions elicited by electrical stimulation of the dorsal midbrain.

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Ribeiro, S J; Ciscato, J G; de Oliveira, R; de Oliveira, R C; D'Angelo-Dias, R; Carvalho, A D; Felippotti, T T; Rebouças, E C C; Castellan-Baldan, L; Hoffmann, A; Corrêa, S A L; Moreira, J E; Coimbra, N C

2005-12-01

the dlSC/dlPAG featuring close axo-somatic and axo-dendritic appositions in both locations. In addition, ultrastructural approaches show inhibitory axo-axonic synapses in MT and inhibitory axo-somatic/axo-axonic synapses in the SNpr. These findings, in addition to the psychopharmacological evidence for the interaction between opioid and GABAergic mechanisms in the cranial aspects of the MT as well as in the mesencephalic tegmentum, offer a neuroanatomical basis of a pre-synaptic opioid inhibition of GABAergic nigrotectal neurons modulating fear in defensive behavior-related structures of the cranial mesencephalon, in a short link, and through a major neural circuit, also in GABA-containing perikarya and axons of nigrotectal neurons.

Doença de Creutzfeldt-Jakob: considerações clínicas, eletrencefalográficas e anatomopatológicas a propósito de uma caso Creutzfeldt-Jakob disease: a case report with clinical, electroencephalographic and neuropathological aspects

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Wilson Luiz Sanvito

1971-03-01

nuclei, the mesencephalon, the pons and the anterior horns. In the cerebelum the granular cells were reduced. Pathogenetic and etiological considerations remained inconclusive, but the slow-virus concept applicable to other neurological diseases (Kuru, subacute sclerosing leuco-encephalitis should not be dismissed from etiopathogenetic considerations of Creutzfeldt-Jakob disease.

Atomoxetine affects transcription/translation of the NMDA receptor and the norepinephrine transporter in the rat brain – an in vivo study

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Udvardi PT

2013-12-01

Full Text Available Patrick T Udvardi,1,2 Karl J Föhr,3 Carolin Henes,1,2 Stefan Liebau,2 Jens Dreyhaupt,4 Tobias M Boeckers,2 Andrea G Ludolph11Department of Child and Adolescent Psychiatry and Psychotherapy, 2Institute of Anatomy and Cell Biology, 3Department of Anaesthesiology, 4Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, GermanyAbstract: Attention-deficit/hyperactivity disorder (ADHD is the most frequently diagnosed neurodevelopmental disorder. The norepinephrine transporter (NET inhibitor atomoxetine, the first nonstimulant drug licensed for ADHD treatment, also acts as an N-methyl-D-aspartate receptor (NMDAR antagonist. The compound's effects on gene expression and protein levels of NET and NMDAR subunits (1, 2A, and 2B are unknown. Therefore, adolescent Sprague Dawley rats were treated with atomoxetine (3 mg/kg, intraperitoneal injection [ip] or saline (0.9%, ip for 21 consecutive days on postnatal days (PND 21–41. In humans, atomoxetine's earliest clinical therapeutic effects emerge after 2–3 weeks. Material from prefrontal cortex, striatum (STR, mesencephalon (MES, and hippocampus (HC was analyzed either directly after treatment (PND 42 or 2 months after termination of treatment (PND 101 to assess the compound's long-term effects. In rat brains analyzed immediately after treatment, protein analysis exhibited decreased levels of the NET in HC, and NMDAR subunit 2B in both STR and HC; the transcript levels were unaltered. In rat brains probed 2 months after final atomoxetine exposure, messenger RNA analysis also revealed significantly reduced levels of genes coding for NMDAR subunits in MES and STR. NMDAR protein levels were reduced in STR and HC. Furthermore, the levels of two SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor proteins, synaptophysin and synaptosomal-associated protein 25, were also significantly altered in both treatment groups. This in vivo study detected atomoxetine's effects

Polysialylated-neural cell adhesion molecule (PSA-NCAM in the human trigeminal ganglion and brainstem at prenatal and adult ages

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Melis Tiziana

2008-11-01

Full Text Available Abstract Background The polysialylated neuronal cell adhesion molecule (PSA-NCAM is considered a marker of developing and migrating neurons and of synaptogenesis in the immature vertebrate nervous system. However, it persists in the mature normal brain in some regions which retain a capability for morphofunctional reorganization throughout life. With the aim of providing information relevant to the potential for dynamic changes of specific neuronal populations in man, this study analyses the immunohistochemical occurrence of PSA-NCAM in the human trigeminal ganglion (TG and brainstem neuronal populations at prenatal and adult age. Results Western blot analysis in human and rat hippocampus supports the specificity of the anti-PSA-NCAM antibody and the immunodetectability of the molecule in postmortem tissue. Immunohistochemical staining for PSA-NCAM occurs in TG and several brainstem regions during prenatal life and in adulthood. As a general rule, it appears as a surface staining suggestive of membrane labelling on neuronal perikarya and proximal processes, and as filamentous and dot-like elements in the neuropil. In the TG, PSA-NCAM is localized to neuronal perikarya, nerve fibres, pericellular networks, and satellite and Schwann cells; further, cytoplasmic perikaryal staining and positive pericellular fibre networks are detectable with higher frequency in adult than in newborn tissue. In the adult tissue, positive neurons are mostly small- and medium-sized, and amount to about 6% of the total ganglionic population. In the brainstem, PSA-NCAM is mainly distributed at the level of the medulla oblongata and pons and appears scarce in the mesencephalon. Immunoreactivity also occurs in discretely localized glial structures. At all ages examined, PSA-NCAM occurs in the spinal trigeminal nucleus, solitary nuclear complex, vestibular and cochlear nuclei, reticular formation nuclei, and most of the precerebellar nuclei. In specimens of different age

Connectivity derived thalamic segmentation in deep brain stimulation for tremor.

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Akram, Harith; Dayal, Viswas; Mahlknecht, Philipp; Georgiev, Dejan; Hyam, Jonathan; Foltynie, Thomas; Limousin, Patricia; De Vita, Enrico; Jahanshahi, Marjan; Ashburner, John; Behrens, Tim; Hariz, Marwan; Zrinzo, Ludvic

2018-01-01

) and ventroposterior (VP) thalamus. The dentate-thalamic area, lay within the M1-thalamic area in a ventral and lateral location. Streamlines corresponding to the DRT connected M1 to the contralateral dentate nucleus via the dentate-thalamic area, clearly crossing the midline in the mesencephalon. Good response was seen when the active contact VTA was in the thalamic area with highest connectivity to the contralateral dentate nucleus. Non-responders had active contact VTAs outside the dentate-thalamic area. We conclude that probabilistic tractography techniques can be used to segment the VL and VP thalamus based on cortical and cerebellar connectivity. The thalamic area, best representing the VIM, is connected to the contralateral dentate cerebellar nucleus. Connectivity based segmentation of the VIM can be achieved in individual patients in a clinically feasible timescale, using HARDI and high performance computing with parallel GPU processing. This same technique can map out the DRT tract with clear mesencephalic crossing.

Aspectos epidemiológicos, clínicos e distribuição das lesões histológicas no encéfalo de bovinos com raiva Epidemiology, clinical signs and distribution of lesions in the brain of rabid cattle

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Ingeborg Maria Langohr

2003-02-01

Full Text Available Foram determinados o tipo, a distribuição e a intensidade das alterações histopatológicas no encéfalo de 25 bovinos com sinais clínicos neurológicos confirmados como casos de raiva pela imunofluorescência direta ou inoculação em camundongos. Foram examinadas secções do encéfalo que incluíram bulbo na altura do óbex, ponte e pedúnculos cerebelares, cerebelo, mesencéfalo na altura dos colículos rostrais, diencéfalo e telencéfalo na altura dos corpos mamilares, e telencéfalo na altura do córtex frontal. A medula cervical foi também examinada em sete desses casos. A duração do curso clínico foi, em média, cinco dias e se caracterizou por paresia ascendente. Não foram observados achados de necropsia específicos. Microscopicamente, o tronco encefálico, o cerebelo e a medula cervical foram mais afetados que o tálamo e o telencéfalo (inluindo o hipocampo. O tipo de lesões era característico de encefalites por infecção viral e incluía encefalomielite não-supurativa com degeneração neuronal, gliose nodular e infiltrado mononuclear perivascular. Corpúsculos de Negri foram encontrados em 17 (68% dos encéfalos examinados. A intensidade e a distribuição das lesões observadas foram correlacionadas com os sinais e a duração da doença clínica.The type, distribution and intensity of the histopathological changes were determined in the brain of 25 cattle which had neurological signs and were confirmed as rabies cases by direct immunofluorescent antibody or biological assay in mice. Sections of the brain examined included medulla at the obex; pons and cerebellar peduncles/ cerebellum; mesencephalon at the level of rostral colliculi; diencephalon and telencephalon through the mamillary bodies; and telencephalon at the level of frontal cortex. The cervical spinal cord was also examined in seven of those cases. The duration of clinical course averaged five days and was characterized by ascendent paresia. Specific

The neurologist facing pain in dementia.

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Álvaro González, Luis Carlos

2015-01-01

Ageing, a common background in dementia, is usually associated with painful disorders. Nevertheless, the use of analgesics is limited due to poor communication. On the other hand, dementia lesions are placed in the nociceptive pathways. For this reason, the painful experience becomes different and distinctive for every lesional type. The lateral nociceptive pathway (lateral thalamic nuclei and primary parietal cortex), which is in charge of the primary pain perception, is preserved in dementia. Thereafter, the shear painful perception, including pain intensity and threshold, remains unmodified. Distinctly, the medial pain pathways are affected by dementia lesions. In this pathway are included: the intralaminar thalamic nuclei, the pons (locus ceruleus:LC), the mesencephalon (periaacueductal grey substance: PGS), the hypothalamus (paraventricular nuclei, mamilary tuberculum) and different areas of the parietal (primary, secondary, operculum), temporal (amigdala, hypoccampus) and frontal (anterior cingular: ACC). As a consequence, the features of pain executed by these areas will be compromised: the cognitive assessment, the mood and emotion inherent to pain, the pain memory or the autonomic responses are modified in dementia. Specifically, in Alzheimer's disease (AD) there is a reduction in the anticipatory and avoidance responses and also a flattening of the autonomic responses. These are essentially secondary to the degenerative changes in the medial temporal (pain memory) and ACC (cognitive and mood aspects) areas. In vascular dementias, there is a cortico-subcortical deafferentation secondary to the white matter lesions. The consequence is the presence of hyperpathy and hyperalgesia. In the frontotemporal dementias, there is a reduction in pain expressivity. It is linked to the lesions in the orbitofrontal and anterior temporal areas, which are responsible of the emotional aspects of pain. In Parkinson's disease, painful conditions are a common characteristic

A phase I trial of etanidazole and hyperfractionated radiotherapy in children with diffuse brain stem glioma

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Dutton, S.C.; Pomeroy, S.L.; Billett, A.L.; Barnes, P.; Kuhlman, C.; Riese, N.E.; Goumnerova, L.; Scott, R.M.; Coleman, C.N.; Tarbell, N.J.

1997-01-01

Objective: Prospective phase I study to evaluate the toxicity and maximum tolerated dose of etanidazole administered concurrently with hyperfractionated radiation therapy (HRT) for children with brain stem glioma. Materials and Methods: Eighteen patients with brain stem glioma were treated with etanidazole and HRT from 1990-1996. Eligibility required MRI confirmation of diffuse glioma of medulla, pons or mesencephalon, and signs/symptoms of cranial nerve deficit, ataxia or long tract signs of ≤ 6 months duration. Cervico-medullary tumors were excluded. Patients (median age 8.5 years; 11 males, 7 females) received HRT to the tumor volume plus a 2 cm margin with parallel opposed 6-15 MV photons. The total dose was 66 Gy for the first 3 patients, followed by 63 Gy over 4.2 weeks (1.5 Gy BID with 6 hours between fractions) for the subsequent 15 patients. Etanidazole was administered as a rapid IV infusion 30 minutes prior to the morning fraction of HRT at doses of 1.8 gm/m2 x 17 doses (30.6 gm/m2) at step 1 to a maximum of 2.4 gm/m2 x 21 doses (50.4 gm/m2) at step 8. Dose escalation was planned with 3 patients at each of the 8 levels. Results: Three patients were treated at each dose level except level 2, on which only one patient was treated. The highest dose level achieved was step 7 which delivered a total etanidazole dose of 46.2 gm/m2. Two patients were treated at this level, and both patients experienced grade 3 toxicity in the form of a diffuse cutaneous rash. Three patients received a lower dose of 42 gm/m2 without significant toxicity, and this represents the maximum tolerated dose (MTD). There were 24 cases of grade 1 toxicity (10 vomiting, 5 peripheral neuropathy, 2 rash, 2 constipation, 1 skin erythema, 1 weight loss, 3 other), eleven cases of grade 2 toxicity (4 vomiting, 2 skin erythema, 2 constipation, 1 arthalgia, 1 urinary retention, 1 hematologic), and four grade b 3 toxicities (2 rash, 1 vomiting, 1 skin desquamation). Grade 2 or 3 peripheral

The treatment of Parkinson's disease with dopamine agonists

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Frank, Wilhelm

2008-06-01

Full Text Available Parkinson’s disease is a chronic degenerative organic disease with unknown causes. A disappearance of cells with melanin in the substantia nigra is considered as biological artefact of the disease, which causes a degenerative loss of neurons in the corpus striatum of mesencephalon. This structure produces also the transmitter substance dopamine. Due to this disappearance of cells dopamine is not produced in a sufficient quantity which is needed for movement of the body. The questions of this report are concerned the efficiency and safety of a treatment with dopamine agonists. Furthermore the cost-effectiveness is investigated as well as ethic questions. The goal is to give recommendation for the use of dopamine agonists to the German health system. A systematic literature search was done. The identified studies have different methodological quality and investigate different hypothesis and different outcome criteria. Therefore a qualitative method of information synthesis was chosen. Since the introduction of L-Dopa in the 1960´s it is considered as the most effective substance to reduce all the cardinal symptoms of Parkinson disease. This substance was improved in the course of time. Firstly some additional substances were given (decarbonxylase inhibitors, catechol-o-transferase inhibitors (COMT-inhibitors, monoaminoxydase-inhibitors (MAO-inhibitors and NMDA-antagonists (N-Methyl-d-aspartat-antagonists. In the practical therapy of Parkinson dopamine agonists play an important role, because they directly use the dopamine receptors. The monotherapy of Parkinson disease is basically possible and is used in early stages of the disease. Clinical practise has shown, that an add on therapy with dopamine agonists can led to a reduction of the dose of L-dopa and a reduction of following dyskinesia. The studies for effectiveness include studies for the initial therapy, monotherapy and add-on-therapy. Basically there is a good effectiveness of dopamine

Connectivity derived thalamic segmentation in deep brain stimulation for tremor

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Harith Akram

(VL and ventroposterior (VP thalamus. The dentate-thalamic area, lay within the M1-thalamic area in a ventral and lateral location. Streamlines corresponding to the DRT connected M1 to the contralateral dentate nucleus via the dentate-thalamic area, clearly crossing the midline in the mesencephalon. Good response was seen when the active contact VTA was in the thalamic area with highest connectivity to the contralateral dentate nucleus. Non-responders had active contact VTAs outside the dentate-thalamic area. We conclude that probabilistic tractography techniques can be used to segment the VL and VP thalamus based on cortical and cerebellar connectivity. The thalamic area, best representing the VIM, is connected to the contralateral dentate cerebellar nucleus. Connectivity based segmentation of the VIM can be achieved in individual patients in a clinically feasible timescale, using HARDI and high performance computing with parallel GPU processing. This same technique can map out the DRT tract with clear mesencephalic crossing. Keywords: Diffusion weighted imaging, DWI, Connectivity, Parkinson's disease, PD, Ventrointermedialis, VIM, Dentato-rubro-thalamic tract, DRT, Ventrolateral nucleus, VL, Dentate nucleus, Tremor, Deep brain stimulation, DBS

Refluxo gastroesofágico participando da cascata cognitiva do pânico Gastroesophageal reflux participating on panic cognitive cascade

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Kalil Duailibi

2008-01-01

with elimination of the panic crises. The acute thoracic pain of the GR is interpreted as a near threat, causing uncertainty regarding an unwell feeling with hyperventilation, acting as a trigger of the panic cognitive cascade, in the dorsal mesencephalon. The esophagic mucosa inflammation is interpreted as a distal threat, stimulating the amygdale and generating anticipated anxiety, increasing stress hormones. According to Deakin-Graeff model, even though 5HT inhibits the panic attack and stimulates the anticipated anxiety, the panic disorder stimulates the latter through dorsal raphe nucleus. In conclusion, the association between PD and GR should be better identified in order that the correct diagnosis and adequate treatment is achieved.

Meningoencefalite por Listeria monocytogenes em ovinos Meningoencephalitis in sheep caused by Listeria monocytogenes

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Daniel R. Rissi

2010-01-01

fed with silage. In three farms there were close contact among affected sheep and other species. Clinical signs were characterized by recumbency (7/7, head tilt (4/7, incoordination (3/7, depression (3/7, circling (2/7, unilateral blindness, wasting, fever, midriasis, paddling, opisthotonus, hind or hind and fore limb paralysis, drooling, and muscle tremors (1/7 each. Clinical evolution varied from 12 hours to three days. Histological findings consisted of predominantly unilateral, microabscedative encephalitis with variable degrees of gliosis and degenerative lesions characterized by axonal spheroids and infiltration by Gitter cells. These lesions were observed extending from medulla oblongata to mesencephalon. Listeria monocytogenes antigen was showed by imunohistochemistry in routinely processed sections of brainstem from all seven affected sheep. The diagnostic was based on epidemiological, clinical, and pathological findings and confirmed by immunohistochemistry (IHQ using polyclonal anti-L. monocytogenes antibody.

Neuropatologia da cinomose canina: 70 casos (2005-2008

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Marcia C. Silva

2009-08-01

distemper. Cases were grouped according to the age of the dogs and classified according to the evolution of the lesions. It was possibly to conclude that: (1 the encephalomyelitis induced by canine distemper virus is more prevalent in puppies and adults; (2 gross lesions in the CNS occur infrequently; (3 the brain is more frequently affected than the spinal cord; (4 the five anatomical sites of the rain more frequently affected are, in decreasing order of frequency, cerebellum, diencephalon, frontal lobe of telencephalon, pons and mesencephalon; (5 the anatomical site more frequently affected in the spinal cord is the cervical (C1-C5 segment; (6 subacute and chronic lesions are more common than acute ones; (7 demyelization is the more prevalent lesion and occur mainly in the cerebellum, pons and diencephalons, usually associated with astrogliosis and non-suppurative inflammation; (8 in most cases with astrogliosis, gemistocytic astrocytes are observed, frequently with syncitia formation; (9 non-suppurative leptomeningitis, malacia and cortical neuronal necrosis are moderately frequent in the brain and less so in the spinal cord; (10 inclusion bodies are frequent in the brain; occur mainly in astrocytes and less frequently in neurons, however independently of the affected cell they occur mainly in the nucleus; (11 a classification of canine distemper encephalitis based in age-related clinical syndromes it is not accurate.

Intoxicação experimental por Phalaris angusta (Gramineae em bovinos Experimental poisoning by Phalaris angusta (Gramineae in cattle

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Renato Silva de Sousa

1999-07-01

treatment groups. Group I calves were fed only P. angusta. Group II calves were fed a mixture of 75 % of P. angusta and 25% of oat (Avena sativa and ryegrass (Lolium multiflorum, whereas group III calves received a mixture of 50% of P.angusta and 50% of oat and ryegrass. Group IV calves received only oat and ryegrass and served as controls. P. angusta was toxic for calves. One group I calf died 34 days after the beginning of the ingestion of the plant, and the other calves were euthanatized in extremis 18 to 32 days after de beginning of the experiment. The main clinical signs were locomotor disorders, generalized tremors, frequent falls, and convulsions. Gross findings were confined to the brain and consisted of focal areas of green-bluish discoloration in the thalamus, mesencephalon, and medulla oblongata. Microscopic lesions were characterized by the presence of a intracytoplasmic yellow-brown indole-like pigment in neurons from grossly affected areas. Ultrastructural changes consisted of swollen lysosomes containing membranous material with variable orientation and density. The amount of ingested P. angusta was not a determinant factor for the severity of clinical signs and lesions. The extension of gross and microscopic lesions was not directly related with the intensity of the clinical signs. P. angusta was exclusively neurotoxic and should be considered as a differential diagnosis in cases of neurological disease of cattle with clinical signs consistent with tremorgenic syndrome.