RESUMO
Rapid improvement of depressive symptoms occurs after the administration of the NMDA antagonist ketamine. Ketamine administration is accompanied by an increase in GLX (sum-peak of glutamate, glutamine (GLN) and GABA) and GLN in the brain, as measured by magnetic-resonance (MR) spectroscopy. In healthy subjects, we observed an increase in GLX and GLN levels after total sleep deprivation (TSD), which has a rapid antidepressant effects. We examined, if an increase in GLX or GLN is related to the therapeutic effect of TSD. We examined 13 patients with major depression by means of proton MR spectroscopy (field strength: 1.5T) before and after 24h of TSD. Two anatomical areas (dorsolateral prefrontal cortex (DLPC) and parieto-occipital cortex (POC)) were studied. In the DLPC TSD did not change GLX or its elements, whereas the total creatine and choline signal increased marginally. No change could be observed in the POC. For further exploration we took gender and the presence of vegetative characteristics of melancholic depression into account, i.e. the presence of early morning awakening, appetite and weight loss was taken into account, to define vegetative melancholia (VM). TSD led to an increase in GLX and GLN in the DLPC only of male patients. In patients with VM an increase in GLN occurred in this area. The low field strength limits the accuracy for GLX and GLN estimates. Despite the exploratory nature of the study, it nevertheless supports earlier data on the importance of glutamatergic neurotransmission and furthermore of gender and/or vegetative features in depression.
Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Privação do Sono/fisiopatologia , Adulto , Idoso , Análise de Variância , Antidepressivos/administração & dosagem , Colina/metabolismo , Creatina/metabolismo , Transtorno Depressivo Maior/metabolismo , Transtorno Depressivo Maior/psicologia , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Espectroscopia de Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Lobo Occipital/efeitos dos fármacos , Lobo Occipital/metabolismo , Lobo Parietal/efeitos dos fármacos , Lobo Parietal/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Escalas de Graduação Psiquiátrica , Fatores Sexuais , Resultado do Tratamento , Ácido gama-Aminobutírico/metabolismoRESUMO
Altered corticosteroid milieu induces changes in hippocampal volume, neuronal structure, neurochemistry and cognitive function in humans and rodents. This in vivo magnetic resonance spectroscopy (1H MRS) and imaging (MRI) study investigated whether long-term alterations of the corticosteroid milieu cause: (i) metabolic and/or (ii) structural changes of the rat hippocampus. Therefore, hypocortisolism was induced by adrenalectomy (ADX), normocortisolism by ADX with low-dose corticosterone replacement, and hypercortisolism by ADX and high-dose dexamethasone treatment (for 11 weeks, respectively). All groups including a control group (n=23) were studied by in vivo 1H MRS and MR volumetry. Effects of treatment on normalized hippocampal metabolites and volumes were tested for significance using one-factorial multivariate analysis of variance (MANOVA). Hypercortisolemic rats revealed significantly elevated glutamate. Hypocortisolemic rats showed significantly decreased myo-inositol ratio levels, and were associated with significantly reduced normalized hippocampal volumes. Our findings suggest chronic hypercortisolism to be associated with glutamate-mediated excitotoxicity in the absence of volumetric abnormalities. In contrast, hypocortisolism appears to be associated with neurodegenerative processes, altered astrocytic metabolism but preserved neuronal density.
Assuntos
Metabolismo Energético/fisiologia , Hipocampo/fisiologia , Hidrocortisona/fisiologia , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Animais , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Atrofia , Colina/metabolismo , Creatina/metabolismo , Dexametasona/farmacologia , Metabolismo Energético/efeitos dos fármacos , Glucocorticoides/farmacologia , Ácido Glutâmico/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Inositol/metabolismo , Masculino , Análise Multivariada , Ratos , Ratos WistarRESUMO
The cannabinoid receptor type 1 (CB1) and its endogenous ligands, the endocannabinoids, are involved in the regulation of food intake. Here we show that the lack of CB1 in mice with a disrupted CB1 gene causes hypophagia and leanness. As compared with WT (CB1+/+) littermates, mice lacking CB1 (CB1-/-) exhibited reduced spontaneous caloric intake and, as a consequence of reduced total fat mass, decreased body weight. In young CB1-/- mice, the lean phenotype is predominantly caused by decreased caloric intake, whereas in adult CB1-/- mice, metabolic factors appear to contribute to the lean phenotype. No significant differences between genotypes were detected regarding locomotor activity, body temperature, or energy expenditure. Hypothalamic CB1 mRNA was found to be coexpressed with neuropeptides known to modulate food intake, such as corticotropin-releasing hormone (CRH), cocaine-amphetamine-regulated transcript (CART), melanin-concentrating hormone (MCH), and preproorexin, indicating a possible role for endocannabinoid receptors within central networks governing appetite. CB1-/- mice showed significantly increased CRH mRNA levels in the paraventricular nucleus and reduced CART mRNA levels in the dorsomedial and lateral hypothalamic areas. CB1 was also detected in epidydimal mouse adipocytes, and CB1-specific activation enhanced lipogenesis in primary adipocyte cultures. Our results indicate that the cannabinoid system is an essential endogenous regulator of energy homeostasis via central orexigenic as well as peripheral lipogenic mechanisms and might therefore represent a promising target to treat diseases characterized by impaired energy balance.
Assuntos
Apetite/fisiologia , Canabinoides/metabolismo , Metabolismo Energético , Ácidos Graxos Insaturados/fisiologia , Lipídeos/biossíntese , Receptores de Droga/fisiologia , Adipócitos/metabolismo , Animais , Moduladores de Receptores de Canabinoides , Hormônio Liberador da Corticotropina/genética , Hormônio Liberador da Corticotropina/fisiologia , Ingestão de Alimentos/fisiologia , Expressão Gênica , Hipotálamo/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neuropeptídeos/genética , Neuropeptídeos/fisiologia , Obesidade/fisiopatologia , Obesidade/terapia , Fenótipo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Canabinoides , Receptores de Droga/deficiência , Receptores de Droga/genética , Magreza/fisiopatologiaRESUMO
In depressed patients as well as healthy controls, a positive relationship between hippocampal volume and trait anxiety has been reported. This study sought to explore the possible inter-relation between hippocampal volume and trait anxiety further. Magnetic resonance imaging at 7 T was used to measure hippocampal volumes in a rat model of extremes in trait anxiety (experiment 1) and in a Wistar population with normal anxiety-related behavior (experiment 2). In addition to anxiety-related behavior, potentially confounding factors (depression-like, exploratory, and locomotor behavior) were assessed. Experiment 1 globally supported the hypothesis of a positive relationship between hippocampus volume and trait anxiety but did not allow for ruling out possible confounds arising from cosegregation of other behavioral traits. Experiment 2 yielded strong evidence for a negative relationship which was specific for trait anxiety. Thus, the relationship between hippocampal volume and anxiety may be more complex than expected. Interestingly, anxiety-related behavior in experiment 2 had a stronger influence on hippocampal volume than depression-like behavior. In the light of hippocampal volume loss in anxiety disorder and frequent comorbidity of anxiety and depression, this finding suggests that further research into the relationship between anxiety and hippocampal volume may be critical for understanding hippocampal contributions to normal and pathological behavior.
Assuntos
Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/fisiopatologia , Atrofia/diagnóstico , Atrofia/fisiopatologia , Hipocampo/patologia , Hipocampo/fisiopatologia , Animais , Transtornos de Ansiedade/complicações , Atrofia/etiologia , Transtorno Depressivo/complicações , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/fisiopatologia , Modelos Animais de Doenças , Imageamento por Ressonância Magnética , Masculino , Vias Neurais/patologia , Vias Neurais/fisiopatologia , RatosRESUMO
BACKGROUND AND PURPOSE: Acute occlusion of the carotid-T is associated with large ischemic lesions, poor outcome and up to 53 % mortality with conservative therapy. Endovascular mechanical thrombectomy (EMT) is a promising alternative treatment of large vessel occlusion. Here, we examine feasibility, safety and efficiency of EMT in acute ischemic stroke due to carotid-T-occlusion. METHODS: Single centre, retrospective analysis of 51 consecutive patients with acute occlusion of the carotid-T, treated by EMT within 6 h after symptom onset. Most patients (42/51) were treated with stentretrievers, 33 with stentretrievers only. Recanalization was assessed by the Thrombolysis in Cerebral Infarction (TICI) score. Early and mid-term clinical outcome was evaluated by National Institutes of Health Stroke Scale (NIHSS)- and modified Rankin Scale mRS-scores, respectively. RESULTS: Successful recanalization (TICI 2b/3) was achieved in 78.4 % (40/51). Good clinical outcome (mRS 0-2) was observed in 24.4 % of patients, and only in patients treated successfully (TICI 2b/3). Stentretrievers yielded higher recanalization rates and better clinical outcomes than non-stentretriever devices. A total of 12 patients died (29.3 %) during the 90-day observation period. Clinically relevant procedure-related complications occurred in two patients, consisting in one vessel perforation with a microwire, and one symptomatic parenchymal haemorrhage after initiation of antiplatelet therapy following the inadvertent detachment of a stentretriever. Another symptomatic haemorrhage, not directly procedure-related, occurred in one additional patient. CONCLUSION: EMT in acute carotid-T-occlusion is efficient, yielding high recanalization rates, and reasonably safe, with a low rate of clinically relevant complications. Successful recanalization seems to be a prerequisite for good clinical outcome in this severe condition.
Assuntos
Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/cirurgia , Hemorragia Cerebral/etiologia , Angiografia por Tomografia Computadorizada/métodos , Trombólise Mecânica/efeitos adversos , Trombólise Mecânica/métodos , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia Intervencionista/métodos , Estudos Retrospectivos , Cirurgia Assistida por Computador/métodos , Resultado do Tratamento , Adulto JovemRESUMO
Continued efforts are undertaken to develop animal models of schizophrenia with translational value in the quest for much needed novel drugs. Existing models mimic specific neurobiological aspects of schizophrenia, but not its full complexity. Here, we used proton magnetic resonance spectroscopy ((1)H-MRS) to assess the metabolic profile in the prefrontal cortex (PFC) of two established models, rearing in social isolation and acute N-methyl-D-aspartate receptor (NMDA-R) antagonism and their combination. Rats reared in social isolation or group housed underwent (1)H-MRS at baseline and dynamically after ketamine challenge (25mg/kg, intraperitoneal) under isoflurane anesthesia. A 7 T animal scanner was used to perform spectra acquisition from the anterior cingulate/medial PFC. LCModel was used for metabolite quantification and effects of rearing and ketamine injection were analyzed. Social isolation did not lead to significant differences in the metabolic profile of the PFC at baseline. Ketamine induced a significant increase in glutamine in both groups with significance specifically reached by the group-housed animals alone. Only rats reared in social isolation showed a significant 11% γ-aminobutyric acid (GABA) decrease. This study provides preliminary evidence that social interactions in early life predict the glutamatergic and GABAergic response to acute NMDA-R blockade. The similarity between the prefrontal GABA reduction in patients with schizophrenia and in rats reared as social isolates after challenge with ketamine suggests good potential translational value of this combined animal model for drug development.
Assuntos
Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Ketamina/farmacologia , Córtex Pré-Frontal/metabolismo , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Esquizofrenia/metabolismo , Psicologia do Esquizofrênico , Isolamento Social , Ácido gama-Aminobutírico/metabolismo , Animais , Modelos Animais de Doenças , Ácido Glutâmico/efeitos dos fármacos , Glutamina/efeitos dos fármacos , Giro do Cíngulo/efeitos dos fármacos , Giro do Cíngulo/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Espectroscopia de Prótons por Ressonância Magnética , Ratos , Ácido gama-Aminobutírico/efeitos dos fármacosRESUMO
PURPOSE: Obesity is a worldwide pandemic, and obese patients face an increased risk of developing acute respiratory distress syndrome (ARDS). Prone positioning (PP) is a frequently used intervention in the treatment of ARDS. There are no data describing the impact of PP on morbidity and mortality in abdominally obese patients. We report our observations in abdominally obese ARDS patients treated with PP. MATERIALS AND METHODS: Patients with ARDS (n=82) were retrospectively divided into 2 groups characterized by presence (n=41) or absence (n=41) of abdominal obesity as defined by a sagittal abdominal diameter of 26 cm or more. RESULTS: There was no difference in cumulative time abdominally obese patients were placed in prone position from admission to day 7 (41.0 hours [interquartile range, 50.5 hours] vs 39.5 hours [interquartile range, 61.5 hours]; P=.65) or in overall intensive care unit mortality (34% vs 34%; P=1). However, abdominally obese patients developed renal failure (83% vs 35%; P<.001) and hypoxic hepatitis (22% vs 2%; P=.015) more frequently. A significant interaction effect between abdominal obesity and prone position with respect to mortality risk (likelihood ratio, P=.0004) was seen if abdominally obese patients were treated with prolonged cumulative PP. CONCLUSION: A cautious approach to PP should be considered in abdominally obese patients.
Assuntos
Obesidade Abdominal/complicações , Posicionamento do Paciente , Decúbito Ventral , Síndrome do Desconforto Respiratório/mortalidade , Síndrome do Desconforto Respiratório/terapia , Adulto , Feminino , Hepatite/etiologia , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Obesidade Abdominal/mortalidade , Insuficiência Renal/etiologia , Estudos Retrospectivos , Estatísticas não Paramétricas , Fatores de TempoRESUMO
BACKGROUND: Secondary sclerosing cholangitis is a severe disease of the biliary tract. Over the last decade, several cases of sclerosing cholangitis in critically ill patients (SC-CIP) were reported. Reports in the literature so far are characterized by a wide variety of underlying causes of critical illness, thereby hindering a risk-factor analysis. We report on a homogenous cohort of critically ill patients with influenza A (H1N1) pneumonia and severe acute respiratory distress syndrome (ARDS), of whom a subgroup developed sclerosing cholangitis, allowing for probing of risk factors associated with SC-CIP. METHODS: Twenty-one patients (5 female, 16 male, 46.3 ± 10.8 years) with severe ARDS due to H1N1 pneumonia were retrospectively divided into two groups, characterized by the presence (n = 5) and absence of SC-CIP (n = 16). A large array of clinical data, laboratory parameters, and multi-detector computed tomography-derived measures were compared. RESULTS: Both patient groups showed severe pulmonary impairment. Severity of disease on admission day and during the first 14 days of treatment showed no difference. The patients developing SC-CIP had a higher body mass index (BMI) (37.4 ± 6.0 kg/m(2) vs. 29.3 ± 6.8 kg/m(2); P = 0.029) and a higher volume of intraperitoneal fat (8273 ± 3659 cm(3) vs. 5131 ± 2268 cm(3); P = 0.033) and spent a longer cumulative period in the prone position during the first 14 days (165 ± 117 h vs. 78 ± 61 h; P = 0.038). CONCLUSION: Our results suggest that obesity, intraperitoneal fat volume, and a longer cumulative duration spent in the prone position may put patients with ARDS at risk of developing SC-CIP. These results lead us to propose that the prone position should be carefully deployed, particularly in abdominally obese patients, and that frequent checks be made for early hepatic dysfunction.
Assuntos
Colangite Esclerosante/etiologia , Vírus da Influenza A Subtipo H1N1/patogenicidade , Influenza Humana/complicações , Obesidade Abdominal/complicações , Síndrome do Desconforto Respiratório/etiologia , Adulto , Índice de Massa Corporal , Colangite Esclerosante/virologia , Estado Terminal , Feminino , Humanos , Influenza Humana/patologia , Unidades de Terapia Intensiva , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Pneumonia Viral/patologia , Decúbito Ventral , Síndrome do Desconforto Respiratório/patologia , Síndrome do Desconforto Respiratório/virologia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
We have previously shown that repeated exposure to mild novel cage stress prevents the onset of recent contextual fear memory deficits and attenuated amyloid deposition in the TASTPM mouse model of Alzheimer's disease. Here, we extended this investigation to remote contextual fear memory and extinction. TASTPM and wild-type mice acquired contextual fear at 4 months of age. Retention and extinction of contextual fear were assessed at 5.5 months prior to in vivo MRI assessment of regional T2 relaxation times and brain volumes followed by immunostaining to determine amyloid plaque load. Remote contextual fear memory was preserved in TASTPM mice regardless of the stress condition. Stress impaired extinction in wild-type mice but facilitated this process in TASTPM mice. Genotype-dependent effects of stress were observed on regional T2 times which were prolonged in the subiculum and thalamus of stressed TASTPM, possibly reflecting reduced amyloid pathology. Amyloid plaque load was particularly decreased in the retrosplenial cortex of stressed TASTPM mice, which also showed an overall reduction in the number of diffuse plaques. These findings support the hypothesis that repeated mild levels of stress induced by novel activities can delay the progression of pathological changes relevant to Alzheimer's disease.