RESUMO
PURPOSE: Long static or intense dynamic apnoea-like high-altitude exposure is inducing hypoxia. Adenosine is known to participate to the adaptive response to hypoxia leading to the control of heart rate, blood pressure and vasodilation. Extracellular adenosine level is controlled through the equilibrative nucleoside transporter 1 (ENT-1) and the enzyme adenosine deaminase (ADA). The aim of this study was to determine the control of adenosine blood level (ABL) via ENT-1 and ADA during apnoea-induced hypoxia in elite freedivers was similar to high-altitude adaptation. METHODS: Ten freediver champions and ten controls were studied. Biological (e.g. ENT-1, ADA, ABL, PaO2, PaCO2 and pH) and cardiovascular (e.g. heart rate, arterial pressure) parameters were measured at rest and after a submaximal dry static apnoea. RESULTS: In freedivers, ABL was higher than in control participants in basal condition and increased more in response to apnoea. Also, freedivers showed an ADA increased in response to apnoea. Finally, ENT-1 level and function were reduced for the free divers. CONCLUSION: Our results suggest in freedivers the presence of an adaptive mechanism similar to the one observed in human exposed to chronic hypoxia induced by high-altitude environment.
Assuntos
Adaptação Fisiológica , Adenosina/sangue , Doença da Altitude/metabolismo , Suspensão da Respiração , Mergulho/fisiologia , Transportador Equilibrativo 1 de Nucleosídeo/metabolismo , Adenosina Desaminase/metabolismo , Adulto , Doença da Altitude/fisiopatologia , Pressão Sanguínea , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Hyperbaric oxygen induced in rats a decrease in striatal dopamine levels. Such decrease could be a result of changes in glutamatergic and GABAergic controls of the dopaminergic neurons into the Substantia Nigra Pars Compacta. The aim of this study was to determine the role of gluatamatergic and Gama-Amino-Butyric-Acid neurotransmissions in this alteration. Dopamine-sensitive electrodes were implanted into the striatum under general anesthesia. After one week rest, awaked rats were exposed to oxygen-nitrogen mixture at a partial pressure of oxygen of 3 absolute atmospheres. Dopamine level was monitored continuously (every 3 min) by in vivo voltammetry with multifiber carbon electrodes before and during hyperbaric oxygen exposure. Hyperbaric oxygen induced a decrease in dopamine level in relationship with the increase in partial pressure of oxygen (-40% at 3 ATA). The used of N-Methyl-D-Aspartate, agonist of glutamatergic N-Methyl-D-Aspartate receptors did not improve considerably this change and gabazine antagonist of Gama-Amino-Butyric-Acid-a receptors induced some little alteration of this change. These results suggest the involvement of other mechanisms.
Assuntos
Corpo Estriado/metabolismo , Dopamina/metabolismo , Oxigenoterapia Hiperbárica/métodos , Receptores de GABA-A/fisiologia , Receptores de N-Metil-D-Aspartato/fisiologia , Animais , Agonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas GABAérgicos/farmacologia , Masculino , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/antagonistas & inibidoresRESUMO
Nitrogen narcosis occurs in humans at around 0.4 MPa (4 ATA). Hydrogen narcosis occurs between 2.6 and 3.0 MPa. In rats, nitrogen disturbances occur from 1 MPa and a loss of righting reflex around 4 MPa. Neurochemical studies in striatum of rats with nitrogen at 3 MPa (75% of anesthesia threshold) with differential pulse voltammetry have demonstrated a decrease in dopamine (DA) release by neurons originated from the substantia nigra pars compacta (SNc). Such a decrease is found also with compressed argon, which is more narcotic than nitrogen and with the anesthetic gas nitrous oxide. Inversely, compressed helium with its very low narcotic potency induces DA increase. Microdialysis studies in the striatum have indicated that nitrogen also induces a decrease of glutamate concentration. Nitrogen pressure did not modify NMDA glutamate receptor activities in SNc or striatum but enhanced GABAA receptors activities in SNc. Repetitive exposures to nitrogen narcosis suppressed the DA decrease and induced an increase. This fact and the lack of improvement of motor disturbances did not support the hypothesis of a physiological adaptation. The desensitization of the GABAA receptors on DA cells during recurrent exposures and the parallel long-lasting decrease of glutamate coupled to the increase in NMDA receptor sensitivity suggest a nitrogen neurotoxicity or addiction induced by recurrent exposures. The differential changes produced by inert gases indifferent neurotransmitter receptors would support the binding protein theory.
Assuntos
Corpo Estriado/metabolismo , Dopamina/metabolismo , Narcose por Gás Inerte/metabolismo , Bicamadas Lipídicas/metabolismo , Substância Negra/metabolismo , Adaptação Fisiológica , Anestésicos/metabolismo , Anestésicos/farmacologia , Animais , Anexina A5/metabolismo , Pressão Atmosférica , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/fisiologia , Cristalografia/métodos , Dopamina/análise , Ácido Glutâmico/metabolismo , Hélio/metabolismo , Hélio/farmacologia , Humanos , Hidrogênio/metabolismo , Hidrogênio/farmacologia , Narcose por Gás Inerte/etiologia , Narcose por Gás Inerte/fisiopatologia , Proteínas de Membrana/metabolismo , N-Metilaspartato/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Nitrogênio/metabolismo , Nitrogênio/farmacologia , Ratos , Receptores de GABA-A/metabolismo , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/metabolismo , Substância Negra/efeitos dos fármacos , Urato Oxidase/metabolismoRESUMO
High pressure of helium-oxygen (He-O2) increases the extracellular levels in both serotonine and dopamine in the rat striatum. Some motor symptoms evoked by high pressure (i.e., LMA) are known to be reduced by intrastriatal infusions of D1-like (SCH23390, 1 microM) or D2-like (Sulpiride, 1 microM) dopaminergic antagonists. Other studies have also reported that serotoninergic antagonists reduce the motor perturbation at pressure. However, it remains unknown whether the changes in serotoninergic neurotransmission may contribute to the beneficial effects of intrastriatal administration of a dopaminergic antagonist. The present study reports the effects of SCH23390 and sulpiride on serotonin levels in the striatum of rats exposed to 8 MPa of He-O2. Both sulpiride and SCH23390 reduced pressure-induced striatal 5-HT increase. Our data suggest that D1-like and D2-like receptors have similar effects on a pressure-evoked striatal 5-HT increase. Thus, reduction in serotoninergic neurotransmission may be one mechanism by which dopaminergic antagonists reduce motor symptoms at pressure.
Assuntos
Pressão Atmosférica , Benzazepinas/farmacologia , Corpo Estriado/efeitos dos fármacos , Antagonistas de Dopamina/farmacologia , Serotonina/metabolismo , Sulpirida/farmacologia , Animais , Cromatografia Líquida de Alta Pressão , Corpo Estriado/metabolismo , Oxigenoterapia Hiperbárica , Masculino , Ratos , Ratos Sprague-Dawley , Estatísticas não ParamétricasRESUMO
Nitrogen at pressure produces a neurological syndrome called nitrogen narcosis. Neurochemical experiments indicated that a single exposure to 3 MPa of nitrogen reduced the concentration of dopamine by 20% in the striatum, a structure involved in the control of extrapyramidal motor activity. This effect of nitrogen was explained by enhanced GABAergic neurotransmission through GABAA receptors and, to a lesser extent, by a decreased glutamatergic input to DA cells through NMDA receptors. The aim of this study was to study, under normobaric conditions, possible alterations of NMDA receptor activity in the substantia nigra pars compacta (SNc) induced by repetitive exposures to nitrogen pressure. Under general anesthesia, male Sprague-Dawley rats were implanted in the striatum with multifiber carbon dopamine-sensitive electrodes and in the SNc with guide cannulae for drug injections. After recovery from surgery, the striatal dopamine level was recorded by voltammetry in freely-moving rats, in normobaric conditions, before and after 5 repetitive exposures to 1MPa of nitrogen (threshold of nitrogen narcosis occurrence in rat). The effect of NMDA receptor activity on DA concentration was investigated using agonist (NMDA) and specific antagonist (AP7) SNc administration. Following repetitive nitrogen exposures, the ability of NMDA to elevate DA concentrations was enhanced. In contrast, after nitrogen exposure AP7 produced a paradoxical increase in DA concentration compared to its inhibitory effect before any exposure. Similar responses were obtained after a single exposure to 3MPa nitrogen. Thus, repetitive exposures to nitrogen narcosis produced a sensitization of postsynaptic NMDA receptors on DA cells, related to a decreased glutamatergic input in SNc. Consequently, successive nitrogen narcosis exposures disrupted ion-channel receptor activity revealing a persistent nitrogen-induced neurochemical change underlying the pathologic process.
Assuntos
Dopamina/metabolismo , Narcose por Gás Inerte/metabolismo , Receptores de N-Metil-D-Aspartato/fisiologia , Substância Negra/metabolismo , 2-Amino-5-fosfonovalerato/análogos & derivados , 2-Amino-5-fosfonovalerato/farmacologia , Animais , Pressão Atmosférica , Eletrodos Implantados , Agonistas de Aminoácidos Excitatórios/farmacologia , Masculino , N-Metilaspartato/farmacologia , Nitrogênio/administração & dosagem , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/agonistas , Receptores de N-Metil-D-Aspartato/antagonistas & inibidoresRESUMO
We investigated the effects of the noble gas argon on the expression of locomotor sensitization to amphetamine and amphetamine-induced changes in dopamine release and mu-opioid neurotransmission in the nucleus accumbens. We found (1) argon blocked the increase in carrier-mediated dopamine release induced by amphetamine in brain slices, but, in contrast, potentiated the decrease in KCl-evoked dopamine release induced by amphetamine, thereby suggesting that argon inhibited the vesicular monoamine transporter-2; (2) argon blocked the expression of locomotor and mu-opioid neurotransmission sensitization induced by repeated amphetamine administration in a short-term model of sensitization in rats; (3) argon decreased the maximal number of binding sites and increased the dissociation constant of mu-receptors in membrane preparations, thereby indicating that argon is a mu-receptor antagonist; (4) argon blocked the expression of locomotor sensitization and context-dependent locomotor activity induced by repeated administration of amphetamine in a long-term model of sensitization. Taken together, these data indicate that argon could be of potential interest for treating drug addiction and dependence.
Assuntos
Anfetamina/farmacologia , Argônio/farmacologia , Locomoção/efeitos dos fármacos , Núcleo Accumbens/efeitos dos fármacos , Receptores Opioides mu/antagonistas & inibidores , Proteínas Vesiculares de Transporte de Monoamina/antagonistas & inibidores , Anfetamina/antagonistas & inibidores , Animais , Sensibilização do Sistema Nervoso Central/efeitos dos fármacos , Sensibilização do Sistema Nervoso Central/fisiologia , Dopamina/fisiologia , Masculino , Núcleo Accumbens/fisiologia , Ratos , Ratos Sprague-Dawley , Proteínas Vesiculares de Transporte de Monoamina/fisiologiaRESUMO
In man, nitrogen narcosis is characterized by euphoria, impaired cognitive function, neuromuscular incoordination and, ultimately, loss of consciousness. Because of the motor movement disorders, we chose to study the nigrostriatal system, whose major function is to regulate the extrapyramidal nervous system. The purpose of this investigation was to monitor changes in extracellular levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum of conscious rats, using intracerebral microdialysis. Results show a 40% decrease in extracellular DA concentration, a 59% increase in extracellular DOPAC and an increase in HVA starting with exposure to the nitrogen mixture. Thirty minutes after the beginning of the exposure, a compensation phase took place. HVA returns to its initial basal value, and levels of DOPAC and DA returned towards normal but never reached their initial values. These results contrast with those observed during the High Pressure Neurological Syndrome (HPNS, 5.1 MPa of helium pressure) in which there is a significant increase in extracellular DA. Therefore, some of the symptoms of nitrogen narcosis may be linked with the decrease in the extracellular DA levels.
Assuntos
Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Dopamina/metabolismo , Ácido Homovanílico/metabolismo , Narcose por Gás Inerte/fisiopatologia , Neostriado/efeitos dos fármacos , Animais , Hélio , Masculino , Microdiálise , Neostriado/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
In mammals high pressure of helium-oxygen (He-O2) breathing mixture leads to the high pressure neurological syndrome (HPNS) which includes a set of behavioural disorders such as locomotor and motor hyperactivity (LMA) and myoclonia. In rats, i.c.v. administrations of competitive NMDA antagonists decrease some of these symptoms suggesting that He-O2 pressure could enhance NMDA neurotransmission within the central nervous system. More recently, we have shown using microdialysis that the extracellular glutamate level is increased in the striatum by He-O2 pressure. Neurochemical data have suggested that this structure is probably involved in the LMA development but not in the myoclonia expression. When considering myoclonia, recent neuropathological studies performed at normal pressure in humans suggest that the globus pallidus extern (equivalent to the globus pallidus in the rat) could be involved in this behavioural disorder. The aim of this study was to compare the role of striatal and pallidal NMDA activity on the LMA development and the myoclonia expression in the model of rat exposed to 8 MPa of He-O2 mixture. The intrastriatal administration of D(-)-2-amino-7-phosphonoheptanoic acid (2-APH) (10 nmol/slide) reduced the LMA development but only slightly reduced myoclonia. In contrast, the intrapallidal administration of 2-APH (10 nmol/slide) reduced both LMA and myoclonia. These results suggest that the LMA development requires NMDA activity at both striatal and pallidal level. In contrast, the myoclonia expression mainly requires NMDA activity at pallidal level. Consequently, NMDA neurotransmission at input and output levels of the striato-pallidal pathway play different roles in some of the behavioural disorders induced by He-O2 pressure.
Assuntos
Pressão Atmosférica , Corpo Estriado/metabolismo , Globo Pálido/metabolismo , Atividade Motora/fisiologia , N-Metilaspartato/metabolismo , 2-Amino-5-fosfonovalerato/análogos & derivados , 2-Amino-5-fosfonovalerato/farmacologia , Animais , Anticonvulsivantes/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Síndrome Neurológica de Alta Pressão/fisiopatologia , Masculino , Atividade Motora/efeitos dos fármacos , Mioclonia/etiologia , Mioclonia/fisiopatologia , Ratos , Ratos Sprague-DawleyRESUMO
The purpose of this study is to investigate the in vivo tumoral brain metabolism in free moving rats using microdialysis. Cells from C6 glioma cell line were inoculated in one striatum 15 days before the microdialysis experimentation. Then, using a new system allowing perfusion of several microdialysis probes in free moving rat, normalised dialysate levels of glucose, lactate and pyruvate were monitored in both glioma and control striatum. At the end of the procedure, animals were sacrificed for histological study. Data shows that probe functioning is similar in both tissues. The results for normalised glucose level were in striatum control: 2.14 mM, in tumoral striatum: 1.71 mM (P>0.1); for lactate, respectively, 0.86 and 1.65 mM (P<0.05) and for pyruvate, respectively, 65.56 and 140. 94 microM (P<0.05). This data clearly shows a significant increase of pyruvate and lactate in tumoral striatum compared to normal striatum, correlating previous in vitro studies on glioma metabolism. We conclude that this microdialysis technique is of value in tumoral brain and could constitute an interesting tool for a better understanding of glioma metabolism.
Assuntos
Neoplasias Encefálicas/metabolismo , Corpo Estriado/metabolismo , Glioma/metabolismo , Glucose/metabolismo , Ácido Láctico/metabolismo , Microdiálise/métodos , Ácido Pirúvico/metabolismo , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Células Tumorais CultivadasRESUMO
When human divers and experimental animals are exposed to high pressure of helium-oxygen mixture, they develop the high pressure neurological syndrome, characterized by nausea, vertigo, tremor, myoclonus, EEG modifications and convulsions. Free-moving rats were stereotaxically implanted in the anterior caudate nucleus with a microdialysis probe to measure dopamine, dihydroxyphenylacetic acid and homovanillic acid levels during different phases of a simulated dive up to 5.1 MPa. Compression was found to cause an increase in extracellular dopamine and dihydroxyphenylacetic acid concentrations, but not in homovanillic acid. This represents a specific effect of high pressure on the dopaminergic pathway. Recent findings on D2 autoreceptors, showing a decrease in receptor affinity under pressure, allow us to conclude that pressure increases dopamine synthesis through a direct action on D2 autoreceptors.
Assuntos
Corpo Estriado/metabolismo , Dopamina/metabolismo , Síndrome Neurológica de Alta Pressão/metabolismo , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Animais , Diálise , Ácido Homovanílico/metabolismo , Masculino , Vias Neurais/fisiologia , Ratos , Ratos Sprague-Dawley , Técnicas EstereotáxicasRESUMO
In rat, helium pressures induce locomotor and motor activity which requires dopaminergic and N-methyl-D-aspartate (NMDA) receptor activities at striatal level. However, biochemical studies have suggested that pressure exposure may increase striatal glutamate level. We used microdialysis technique to study the effects of pressure on glutamate level in the striatum and the effects of local administration of D1 (SCH23390) or D2 (sulpiride) on these changes. Pressures increase both glutamate and glutamine levels in striatal microdialysates. Administration of sulpiride (1 microM) or SCH23390 (1 microM) by reverse microdialysis did not affect significantly pressure induced glutamate increase. So, protective effects of D1 and D2 antagonists against locomotor and motor hyperactivity (LMA) are probably independent of the processes involved in the striatal glutamate increase evoked by pressure.
Assuntos
Corpo Estriado/efeitos dos fármacos , Ácido Glutâmico/efeitos dos fármacos , Glutamina/efeitos dos fármacos , Hélio/farmacologia , Síndrome Neurológica de Alta Pressão/metabolismo , Oxigênio/farmacologia , Animais , Pressão Atmosférica , Benzazepinas/farmacologia , Corpo Estriado/metabolismo , Antagonistas de Dopamina/farmacologia , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Síndrome Neurológica de Alta Pressão/fisiopatologia , Masculino , Microdiálise , Atividade Motora , Ratos , Ratos Sprague-Dawley , Sulpirida/farmacologiaRESUMO
High pressure is known as a basic etiological factor underlying central nervous system changes known as the high pressure neurological syndrome (HPNS). In the rat, HPNS includes behavioural disturbances including locomotor and motor hyperactivities (LMA) linked to a striatal dopamine (DA) increase. Recent findings have shown that intracerebroventricular administration of 5-HT3 or 5-HT1b antagonists decrease both LMA and striatal DA increase suggesting that pressure could enhance the serotonin (5-HT) neurotransmission. In this study, for the first time, the striatal levels of DA and 5-HT were simultaneously monitored using microdialysis in free-moving rats exposed to high pressure. Our results show that the striatal 5-HT level increases during pressure exposure. These data suggest that pressure-induced striatal 5-HT increase could participate in the increasing DA release. Nevertheless, the lack of correlation between striatal DA and 5-HT changes suggests that other processes are involved in the pressure-induced striatal DA increase.
Assuntos
Pressão Atmosférica , Corpo Estriado/química , Dopamina/análise , Serotonina/análise , Animais , Masculino , Microdiálise , Ratos , Ratos Sprague-DawleyRESUMO
High pressure induced locomotor and motor hyperactivities (LMA), tremor and myoclonia in rat. The LMA has been reported to be reduced by intracerebroventricular (i.c.v.) administration of dopaminergic receptor antagonists. Moreover, the LMA but not myoclonia correlate with pressure induced striatal dopamine increase. Nevertheless the role of dopaminergic and NMDA receptor activities at striatal level in the development of LMA remained unclear. In this study, the microdialysis technique associated to a behavioural device was used to test the effects of intra-striatal administration of D1 antagonist SCH23390 (1 microM), D2 antagonist sulpiride (1 microM) and NMDA antagonist AP-5 (10 microM) on LMA, tremor and myoclonia expression. Data clearly showed that LMA was drastically reduced by each treatment. In contrast, tremor and myoclonia were poorly affected. These data suggest that both dopaminergic and NMDA receptor activities at striatal level are needed for the full expression of the pressure-induced LMA and confirm that striatal neurotransmission changes are principally involved in this behavioural disorders. At the light of recent studies on dopaminergic neurotransmission and glutamate evoked-NMDA activity, we suggest that blockage of D1 or D2 receptors should reduced the LMA by reducing glutamate-evoked activity.
Assuntos
Antagonistas de Dopamina/uso terapêutico , Antagonistas de Aminoácidos Excitatórios/farmacologia , Síndrome Neurológica de Alta Pressão/tratamento farmacológico , Hipercinese/tratamento farmacológico , Mioclonia/tratamento farmacológico , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Tremor/tratamento farmacológico , 2-Amino-5-fosfonovalerato/farmacologia , 2-Amino-5-fosfonovalerato/uso terapêutico , Animais , Benzazepinas/farmacologia , Benzazepinas/uso terapêutico , Corpo Estriado/efeitos dos fármacos , Antagonistas de Dopamina/farmacologia , Antagonistas dos Receptores de Dopamina D2 , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Síndrome Neurológica de Alta Pressão/fisiopatologia , Hipercinese/fisiopatologia , Masculino , Microdiálise , Mioclonia/fisiopatologia , Ratos , Ratos Sprague-Dawley , Receptores de Dopamina D1/antagonistas & inibidores , Sulpirida/farmacologia , Sulpirida/uso terapêutico , Tremor/fisiopatologiaRESUMO
Reduction of central energy metabolism is a strategy to protect brain against neurotoxic events. The aim of this microdialysis study in rats is to evaluate changes in energy metabolite levels at central level (striatum) comparatively to peripheral level (subcutaneous adipose tissue) during hypothermic barbituric deep-anaesthesia (sodium pentobarbital 60 mg/kg intraperitoneally). At brain level, extracellular glucose increases (+14.9%) while lactate decreases (-16.6%); opposite results were observed at subcutaneous level (-29.2% for glucose and +68.3% for lactate). Lactate/pyruvate ratio remains unchanged at brain level, but increases at subcutaneous level (+73.5%). In light of previous studies on the effects of pentobarbital on regional blood flow and tissue glucose consumption, our data correlates the fact that pentobarbital reduces preferentially brain energetic metabolism. We suggest that those regional effects are explained, at least for a part, by the fact that central isoform glucose transporters (Glut1 and Glut3) are known to be more sensitive to pentobarbital than peripheral isoforms. Such facts can be involved in the protection of brain tissue against ischemic risk due to decreased cerebral blood flow decrease.
Assuntos
Adjuvantes Anestésicos/farmacologia , Encéfalo/efeitos dos fármacos , Glucose/metabolismo , Hipotermia Induzida , Ácido Láctico/metabolismo , Pentobarbital/farmacologia , Ácido Pirúvico/metabolismo , Animais , Encéfalo/metabolismo , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/fisiologia , Masculino , Microdiálise/métodos , Ratos , Ratos Sprague-DawleyRESUMO
Tumoral growth effects on brain circuitry and neurochemical activities remain poorly documented. This study evaluates C6 graft effects on striatal dopaminergic afferent projections at both anatomical and functional levels. Immunohistochemistry was performed to investigate changes in neurofilament (NF), tyrosine hydroxylase (TH) and dopamine transporter (DAT) expression. Dopaminergic turnover was assessed using multiprobe microdialysis in freely-moving rat. In C6 graft striatum, dopamine (DA) catabolites were reduced in glioblastoma (DOPAC: -61%, HVA: -62%). In contrast, the DA level remained unchanged. Staining for NF, TH and DAT was drastically decreased inside the tumor. Our histological data report that striatal tumoral growth is associated with a decrease in the density of dopaminergic endings which can explain, at least in part, the decrease in DA turnover. The decrease in DAT transporter expression and the lack of change in DA level may result from an increase in DA diffusion from the peripheral areas of the tumor. In conclusion, glioblastoma growth has major consequences on the local neuronal circuitry and its neurochemistry. Changes in inter-connections and neurotransmitter turnover may result in abnormal neuronal firing activity and participate in clinical disorders associated with glioblastoma diagnosis.
Assuntos
Vias Aferentes/metabolismo , Neoplasias Encefálicas/metabolismo , Dopamina/metabolismo , Glioma/metabolismo , Glicoproteínas de Membrana , Neostriado/metabolismo , Proteínas do Tecido Nervoso , Plasticidade Neuronal/fisiologia , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Vias Aferentes/patologia , Vias Aferentes/fisiopatologia , Animais , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/fisiopatologia , Modelos Animais de Doenças , Proteínas da Membrana Plasmática de Transporte de Dopamina , Regulação para Baixo/fisiologia , Líquido Extracelular/metabolismo , Glioma/patologia , Glioma/fisiopatologia , Ácido Homovanílico/metabolismo , Imuno-Histoquímica , Masculino , Proteínas de Membrana Transportadoras/metabolismo , Microdiálise , Transplante de Neoplasias , Neostriado/patologia , Neostriado/fisiopatologia , Proteínas de Neurofilamentos/metabolismo , Terminações Pré-Sinápticas/metabolismo , Ratos , Ratos Sprague-Dawley , Células Tumorais Cultivadas , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
In this work, we report a new analysis system to quantify the behavioral disorders observed in the model of the rat submitted to high pressure and monitored by piezoelectric sensor. The major advance consists in a spectral 3D representation of LMA and tremor, which provides a better selectivity than previous systems. This behavioral processing indicated that tremor is characterized by a 7-14 Hz frequency band and LMA by a 20-35 Hz frequency band. The association of this system to the microdialysis technique to simultaneously evaluate the striatal DA level confirms that pressure-induced striatal DA increase is in great part linked to the LMA, and supports the concept of a complex ethiology for this symptom. We conclude that this new behavioral system analysis associated with microdialysis study constitutes a powerful tool to investigate the role of different neurotransmitters in the occurrence of the behavioral components described in the HPNS of rats.
Assuntos
Pressão do Ar , Química Encefálica/fisiologia , Dopamina/fisiologia , Atividade Motora/fisiologia , Psicologia Experimental/instrumentação , Animais , Gráficos por Computador , Dopamina/metabolismo , Espaço Extracelular/metabolismo , Hipercinese/fisiopatologia , Masculino , Microdiálise , Mioclonia/metabolismo , Neostriado/metabolismo , Neurotransmissores/metabolismo , Ratos , Ratos Sprague-Dawley , Tremor/fisiopatologia , VibraçãoRESUMO
Narcosis is a neurological syndrome that reduces capacities of divers. Although this phenomenon appeared at the end of 19th century, the mechanisms are not yet elucidated. The greatest technical problem is that these studies are carried out under hyperbaric conditions. Nitrous oxide is known to be an inducer of narcosis, at atmospheric pressure. The aim of this study is to compare two narcotic environments; a normobaric narcosis under several percentages of nitrous oxide, and an hyperbaric narcosis under 0.9 MPa of Nitrox (N2O2 mixture). This comparison is realized on rats submitted to a fixed-ratio 15 test, in which they have to press a lever to get rewarded. The results show significant performances decreases: the number of pressed lever are reduced by 50% under Nitrox and by 70% under N2O. Nitrous oxide could be considered as a normobaric model of hyperbaric narcosis.
Assuntos
Pressão Atmosférica , Narcose por Gás Inerte/fisiopatologia , Nitrogênio/efeitos adversos , Óxido Nitroso/efeitos adversos , Animais , Condicionamento Operante/efeitos dos fármacos , Modelos Animais de Doenças , Narcose por Gás Inerte/etiologia , Masculino , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Long-Evans , Tempo de Reação , Estatísticas não ParamétricasRESUMO
In three experiments, startle responses to brief intense tone-bursts (30 msec, 110 dB, 6000 Hz) and single pulse (0.1 msec) stimulation of the cochlear nucleus and the nucleus reticularis pontis caudalis are studied under high pressures of heliox (from 0 bar to 50 bars) in the rat. For each rat (N = 12), mean amplitude and latency changes in startle responses (nuchal electromyography and whole-body accelerometry) are compared at normobaric pressure and during compression, at a speed of 100 bar/H. The results indicate that high pressures decrease (50% of control size) tone evoked startle by acting on the peripheral auditory organ, probably through middle and/or inner ear barotrauma. The large increases in electrically-elicited startle (250% of control size) from the cochlear and reticular nuclei, under hyperbaric conditions, suggest that high pressures affect sensorimotor reactivity by excitatory action on synaptic transmission in the relays of the acoustic startle reflex arc at the lower brainstem and spinal levels. Startle latencies remain unaffected by the heliox high pressures studied here.
Assuntos
Nível de Alerta/fisiologia , Doenças do Sistema Nervoso Central/fisiopatologia , Nervo Coclear/fisiopatologia , Síndrome Neurológica de Alta Pressão/fisiopatologia , Ponte/fisiopatologia , Tempo de Reação/fisiologia , Reflexo de Sobressalto/fisiologia , Estimulação Acústica , Animais , Vias Auditivas/fisiopatologia , Masculino , Ratos , Formação Reticular/fisiopatologiaRESUMO
The aim of this work was to study the role of pallidal GABAa and GABAb neurotransmission in the behavioral disorders induced by pressure. The effects of GABAb antagonist 5-aminovalleric acid (5-AVA) or GABAa antagonist gabazine administrations in the globus pallidus (GP) on locomotor and motor hyperactivity (LMA) and myoclonia expressions in the model of the rat submitted to 8 MPa of helium-oxygen breathing mixture were analyzed. The administration of GABAa antagonist gabazine enhances the occurrence of the epileptic seizures, slightly increases LMA but decreases myoclonia. In contrast, the administration of GABAb antagonist 5-AVA decreases both LMA and myoclonia during the compression and the beginning of the holding time at 8 MPa. These data indicate that some behavioral disorders induced by pressure are in relation with GABAergic neurotransmission and establish clearly that GABAa and GABAb receptor mediations have distinct functions in the GP of the rat.
Assuntos
Aminoácidos Neutros/administração & dosagem , Pressão Atmosférica , Antagonistas GABAérgicos/administração & dosagem , Globo Pálido/efeitos dos fármacos , Transtornos Mentais , Piridazinas/administração & dosagem , Animais , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Antagonistas de Receptores de GABA-A , Antagonistas de Receptores de GABA-B , Globo Pálido/fisiologia , Hipercinese/induzido quimicamente , Hipercinese/tratamento farmacológico , Masculino , Transtornos Mentais/induzido quimicamente , Transtornos Mentais/tratamento farmacológico , Mioclonia/induzido quimicamente , Mioclonia/tratamento farmacológico , Ratos , Ratos Sprague-Dawley , Receptores de GABA-A/fisiologia , Receptores de GABA-B/fisiologiaRESUMO
The potential benefit of 100 vol% normobaric oxygen (NBO) for the treatment of acute ischemic stroke patients is still a matter of debate. To advance this critical question, we studied the effects of intraischemic normobaric oxygen alone or in combination with recombinant tissue-plasminogen activator (rtPA) on cerebral blood flow and ischemic brain damage and swelling in a clinically relevant rat model of thromboembolic stroke. We show that NBO provides neuroprotection by achieving cerebral blood flow restoration equivalent to 0.9 mg/kg rtPA through probable direct interaction and facilitation of the fibrinolytic properties of endogenous tPA. In contrast, combined NBO and rtPA has no neuroprotective effect on ischemic brain damage despite producing cerebral blood flow restoration. These results 1) by providing a new mechanism of action of NBO highlight together with previous findings the way by which intraischemic NBO shows beneficial action; 2) suggest that NBO could be an efficient primary care therapeutic intervention for patients eligible for rtPA therapy; 3) indicate that NBO could be an interesting alternative for patients not eligible for rtPA therapy; and 4) caution the use of NBO in combination with rtPA in acute stroke patients.