Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 18 de 18
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Brain Neurosci Adv ; 5: 23982128211036332, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34423137

RESUMO

There is currently no brain atlas available to specifically determine stereotaxic coordinates for neurosurgery in Lister hooded rats despite the popularity of this strain for behavioural neuroscience studies in the United Kingdom and elsewhere. We have created a dataset, which we refer to as 'Ratlas-LH' (for Lister hooded). Ratlas-LH combines in vivo magnetic resonance images of the brain of young adult male Lister hooded rats with ex vivo micro-computed tomography images of the ex vivo skull, as well as a set of delineations of brain regions, adapted from the Waxholm Space Atlas of the Sprague Dawley Rat Brain. Ratlas-LH was produced with an isotropic resolution of 0.15 mm. It has been labelled in such a way as to provide a stereotaxic coordinate system for the determination of distances relative to the skull landmark of bregma. We have demonstrated that the atlas can be used to determine stereotaxic coordinates to accurately target brain regions in the Lister hooded rat brain. Ratlas-LH is freely available to facilitate neurosurgical procedures in the Lister hooded rat.

2.
PLoS One ; 14(2): e0212002, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30789943

RESUMO

Neuroinflammation plays an important role in the pathogenesis of a range of brain disorders. Non-invasive imaging of neuroinflammation is critical to help improve our understanding of the underlying disease mechanisms, monitor therapies and guide drug development. Generally, MRI lacks specificity to molecular imaging biomarkers, but molecular MR imaging based on chemical exchange saturation transfer (CEST) can potentially detect changes of myoinositol, a putative glial marker that may index neuroinflammation. In this pilot study we aimed to investigate, through validation with immunohistochemistry and in vivo magnetic resonance spectroscopy (MRS), whether CEST imaging can reflect the microglial response to a mild inflammatory challenge with lipopolysaccharide (LPS), in the APPSwe/ PS1 mouse model of Alzheimer's disease and wild type controls. The response to the immune challenge was variable and did not align with genotype. Animals with a strong response to LPS (Iba1+, n = 6) showed an increase in CEST contrast compared with those who did not (Iba1-, n = 6). Changes of myoinositol levels after LPS were not significant. We discuss the difficulties of this mild inflammatory model, the role of myoinositol as a glial biomarker, and the technical challenges of CEST imaging at 0.6ppm.


Assuntos
Doença de Alzheimer/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Inositol/metabolismo , Lipopolissacarídeos/efeitos adversos , Proteínas dos Microfilamentos/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Interpretação de Imagem Assistida por Computador , Espectroscopia de Ressonância Magnética , Camundongos , Imagem Molecular , Neuroglia/metabolismo , Projetos Piloto , Regulação para Cima
3.
Behav Brain Res ; 339: 140-152, 2018 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-29175372

RESUMO

NAD metabolism and the NAD biosynthetic enzymes nicotinamide nucleotide adenylyltransferases (NMNATs) are thought to play a key neuroprotective role in tauopathies, including Alzheimer's disease. Here, we investigated whether modulating the expression of the NMNAT nuclear isoform NMNAT1, which is important for neuronal maintenance, influences the development of behavioral and neuropathological abnormalities in htau mice, which express non-mutant human tau isoforms and represent a model of tauopathy relevant to Alzheimer's disease. Prior to the development of cognitive symptoms, htau mice exhibit tau hyperphosphorylation associated with a selective deficit in food burrowing, a behavior reminiscent to activities of daily living which are impaired early in Alzheimer's disease. We crossed htau mice with Nmnat1 transgenic and knockout mice and tested the resulting offspring until the age of 6 months. We show that overexpression of NMNAT1 ameliorates the early deficit in food burrowing characteristic of htau mice. At 6 months of age, htau mice did not show neurodegenerative changes in both the cortex and hippocampus, and these were not induced by downregulating NMNAT1 levels. Modulating NMNAT1 levels produced a corresponding effect on NMNAT enzymatic activity but did not alter NAD levels in htau mice. Although changes in local NAD levels and subsequent modulation of NAD-dependent enzymes cannot be ruled out, this suggests that the effects seen on behavior may be due to changes in tau phosphorylation. Our results suggest that increasing NMNAT1 levels can slow the progression of symptoms and neuropathological features of tauopathy, but the underlying mechanisms remain to be established.


Assuntos
Comportamento Animal/fisiologia , Memória/fisiologia , Nicotinamida-Nucleotídeo Adenililtransferase/genética , Tauopatias/patologia , Atividades Cotidianas , Animais , Modelos Animais de Doenças , Camundongos Knockout , Neurônios/metabolismo , Proteínas tau/metabolismo
4.
Mol Pain ; 122016.
Artigo em Inglês | MEDLINE | ID: mdl-27068285

RESUMO

BACKGROUND: The mechanisms driving osteoarthritic pain remain poorly understood, but there is increasing evidence for a role of the central nervous system in the chronification of pain. We used functional magnetic resonance imaging to investigate the influence of a model of unilateral knee osteoarthritis on nociceptive processing. RESULTS: Four to five weeks post intra-articular injection of monosodium iodoacetate (MIA, 1 mg) into the left knee, Sprague Dawley rats were anesthetized for functional magnetic resonance imaging studies to characterize the neural response to a noxious stimulus (intra-articular capsaicin injection). In a two-arm cross-over design, 5 µM/50 µl capsaicin was injected into either the left knee (n = 8, CAPS-MIA) or right control knee (n = 8, CAPS-CON), preceded by contralateral vehicle (SAL) injection. To assess neural correlates of mechanical hyperalgesia, hindpaws were stimulated with von Frey hairs (8 g: MIA; 15 g: control knee, based on behavioral withdrawal responses). The CAPS-MIA group exhibited significant activation of the periaqueductal gray, unilateral thalamus and bilateral mensencephalon, superior-colliculus, and hippocampus, with no significant activation in the other groups/conditions. Capsaicin injection increased functional connectivity in the mid-brain network and mediodorsal thalamic nucleus, hippocampus, and globus pallidus, which was significantly stronger in CAPS-MIA compared to CAPS-CON groups. Mechanical stimulation of the hyperalgesic (ipsilateral to MIA knee) and normalgesic (contralateral) hindpaws evoked qualitatively different brain activation with more widespread brainstem and anterior cingulate (ACC) activation when stimulating the hyperalgesic paw, and clearer frontal sensory activation from the normalgesic paw. CONCLUSIONS: We provide evidence for modulation of nociceptive processing in a chronic knee osteoarthritis pain model with stronger brain activation and alteration of brain networks induced by the pro-nociceptive stimulus. We also report a shift to a medial pain activation pattern following stimulation of the hyperalgesic hindpaw. Taken together, our data support altered neural pain processing as a result of peripheral and central pain sensitization in this model.


Assuntos
Encéfalo/patologia , Hiperalgesia/complicações , Hiperalgesia/tratamento farmacológico , Iodoacetatos/uso terapêutico , Ácido Iodoacético/uso terapêutico , Osteoartrite do Joelho/tratamento farmacológico , Dor/tratamento farmacológico , Animais , Comportamento Animal , Encéfalo/efeitos dos fármacos , Mapeamento Encefálico , Capsaicina , Modelos Animais de Doenças , Estimulação Elétrica , Hiperalgesia/patologia , Hiperalgesia/fisiopatologia , Injeções Intra-Articulares , Iodoacetatos/farmacologia , Ácido Iodoacético/farmacologia , Imageamento por Ressonância Magnética , Nociceptividade/efeitos dos fármacos , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/fisiopatologia , Dor/complicações , Dor/fisiopatologia , Ratos Sprague-Dawley
5.
Sci Rep ; 6: 19880, 2016 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-26813748

RESUMO

Microglia activation has emerged as a potential key factor in the pathogenesis of Alzheimer's disease. Metabolite levels assessed by magnetic resonance spectroscopy (MRS) are used as markers of neuroinflammation in neurodegenerative diseases, but how they relate to microglial activation in health and chronic disease is incompletely understood. Using MRS, we monitored the brain metabolic response to lipopolysaccharides (LPS)-induced microglia activation in vivo in a transgenic mouse model of Alzheimer's disease (APP/PS1) and healthy controls (wild-type (WT) littermates) over 4 hours. We assessed reactive gliosis by immunohistochemistry and correlated metabolic and histological measures. In WT mice, LPS induced a microglial phenotype consistent with activation, associated with a sustained increase in macromolecule and lipid levels (ML9). This effect was not seen in APP/PS1 mice, where LPS did not lead to a microglial response measured by histology, but induced a late increase in the putative inflammation marker myoinositol (mI) and metabolic changes in total creatine and taurine previously reported to be associated with amyloid load. We argue that ML9 and mI distinguish the response of WT and APP/PS1 mice to immune mediators. Lipid and macromolecule levels may represent a biomarker of activation of healthy microglia, while mI may not be a glial marker.


Assuntos
Doença de Alzheimer/metabolismo , Espectroscopia de Ressonância Magnética , Microglia/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/imunologia , Doença de Alzheimer/patologia , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Modelos Animais de Doenças , Proteína Glial Fibrilar Ácida/metabolismo , Lipopolissacarídeos/imunologia , Masculino , Camundongos , Camundongos Transgênicos , Proteínas dos Microfilamentos/metabolismo , Microglia/imunologia
6.
Magn Reson Med ; 64(4): 967-74, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20715058

RESUMO

The transverse relaxation rate (R(2)) of fresh human blood has been investigated at high and ultrahigh field, to characterize the R(2) dependency on blood sample oxygenation, hematocrit, and Carr-Purcell Meiboom-Gill sequence inter-echo spacing. Data were fitted to chemical exchange and diffusion models to assess their performance at different field strengths. The diffusion model gave a slightly superior fit at both field strengths, but the difference is unlikely to be relevant for the signal to noise ratio achieved in most in vivo experiments. Fitted model parameters were similar to those found in literature.


Assuntos
Algoritmos , Análise Química do Sangue/métodos , Hematócrito/métodos , Espectroscopia de Ressonância Magnética/métodos , Modelos Cardiovasculares , Oxigênio/sangue , Simulação por Computador , Humanos
7.
J Alzheimers Dis ; 20(4): 1049-68, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20413887

RESUMO

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.


Assuntos
Amiloide/genética , Extinção Psicológica/fisiologia , Medo/psicologia , Estresse Psicológico/psicologia , Amiloide/biossíntese , Peptídeos beta-Amiloides/metabolismo , Animais , Química Encefálica/fisiologia , DNA Complementar/biossíntese , DNA Complementar/genética , Discriminação Psicológica/fisiologia , Eletrochoque , Genótipo , Abrigo para Animais , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Memória/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Desempenho Psicomotor , Percepção Espacial/fisiologia , Estresse Psicológico/metabolismo
8.
Hum Brain Mapp ; 28(6): 555-66, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17437283

RESUMO

This article describes a suite of computational approaches suitable for deriving various quantitative phenotypes from structural magnetic resonance (MR) images obtained in rodents and used subsequently in genetic studies of complex traits. We begin by introducing the basic principles of genetic studies of complex traits in experimental models. We then illustrate the use of MR-based computational anatomy in vivo and ex vivo, and in combination with histology. This work was carried out in two inbred strains of rats, namely spontaneously hypertensive rats and Brown Norway rats; these are parental strains of the only existing panel of recombinant inbred strains of rats. The rats were scanned in vivo at two time points (at 8 and 12 weeks of age) and ex vivo (at 12 weeks of age). We describe between-strain differences and across-time changes in brain and kidney volumes, as well as regional variations in brain structure using surface- and deformation-based approaches. We conclude by discussing the power of the population-based computational analysis of MR images, and their fusion with histology, in studies of complex traits.


Assuntos
Mapeamento Encefálico , Encéfalo/anatomia & histologia , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Modelos Genéticos , Fenótipo , Animais , Encéfalo/anormalidades , Processamento de Imagem Assistida por Computador/métodos , Masculino , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos SHR
9.
J Neurosci Methods ; 163(1): 31-7, 2007 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-17368787

RESUMO

Functional magnetic resonance imaging (fMRI) is increasingly being used for animal studies studying the transmission of nociceptive information. Application of noxious mechanical stimuli is widely used for animal and human assessment of pain processing. Any accessory hardware used in animal imaging studies must, however, be sufficiently small to fit in the magnet bore diameter and be non-magnetic. We have developed a system that can apply mechanical stimuli simultaneously with fMRI. This system consists of a standardized instrument to deliver mechanical stimuli (VonFrey monofilament) and a gas-pressured mechanical transducer. These components were integrated with a computer console that controlled the period of stimuli to match acquisition scans. Preliminary experiments demonstrated that the force-stimulus transducer did not influence MRI signal to noise ratio. Mechanical stimulation of the hindpaw significantly increased blood oxygen level dependent (BOLD) signal intensity in several midbrain regions involved in the processing of nociceptive information in the rat (p<0.001, uncorrected for multiple comparisons). This system can be applied to both animal and human imaging studies and has a wide range of applications for studies of nociceptive processing.


Assuntos
Mapeamento Encefálico , Encéfalo/irrigação sanguínea , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Estimulação Física , Animais , Masculino , Oxigênio/sangue , Medição da Dor , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
10.
Pain ; 126(1-3): 35-45, 2006 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-16843597

RESUMO

Functional magnetic resonance imaging (fMRI) of blood oxygen level dependent (BOLD) haemodynamic responses was used to study the effects of the noxious substance capsaicin on whole brain activation in isofluorane anaesthetised rats. Rats (n=8) received intradermal injection of capsaicin (30 microg/5 microl), or topical cream (0.1%) capsaicin and BOLD responses were acquired for up to 120 min. Effects of capsaicin versus placebo cream treatment on the BOLD response to a 15 g mechanical stimulus applied adjacent to the site of cream application were also studied. Both injection and cream application of capsaicin activated brain areas involved in pain processing, including the thalamus and periaqueductal grey (PAG) (p<0.05, corrected for multiple comparisons). Capsaicin also produced increases in BOLD signal intensity in other regions that contribute to pain processing, such as the parabrachial nucleus and superior colliculus. Mechanical stimulation in capsaicin-treated rats, but not placebo-treated rats, induced a significant decrease in BOLD signal intensity in the PAG (p<0.001). These data demonstrate that the noxious substance capsaicin produces brain activation in the midbrain regions and reveals the importance of the PAG in central sensitization.


Assuntos
Analgésicos não Narcóticos/farmacologia , Capsaicina/farmacologia , Imageamento por Ressonância Magnética , Mesencéfalo/efeitos dos fármacos , Mesencéfalo/fisiopatologia , Oxigênio/sangue , Administração Tópica , Analgésicos não Narcóticos/administração & dosagem , Animais , Capsaicina/administração & dosagem , Hiperalgesia/induzido quimicamente , Hiperalgesia/fisiopatologia , Injeções Intradérmicas , Mesencéfalo/irrigação sanguínea , Pomadas , Dor/induzido quimicamente , Dor/fisiopatologia , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Substância Cinzenta Periaquedutal/fisiopatologia , Estimulação Física , Ratos , Ratos Sprague-Dawley , Pele/fisiopatologia , Colículos Superiores/efeitos dos fármacos , Colículos Superiores/fisiopatologia , Tálamo/efeitos dos fármacos , Tálamo/fisiopatologia , Fatores de Tempo
11.
Neurochem Res ; 30(10): 1219-25, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16341583

RESUMO

We have investigated in more detail our previous observations on a form of ischaemic pre-conditioning "metabolic adaptation", i.e.--that sequential metabolic insults (hypoxia followed 40 min later by combined hypoxia + hypoglycaemia, or vice versa) are less injurious (monitored by increased [Ca2+]i and decreased PCr) than the immediate combined insult. We have now observed that the "adaptation" occurs between 10 and 20 min. Pre-treatment of the tissues with 10 microM-MK801 showed that it had no effect on the increase in [Ca2+]i caused by the sequential insult and only partially blocked the increase observed by exposure to the immediate combined insult. Exposure to both the delayed and immediate combined insults with low extracellular Ca2+ resulted in a two-fold increase in [Ca2+]i, similar to the increase observed with normal extracellular Ca2+ in the presence of MK801. The results are discussed in terms of the possible origins of the increases in [Ca2+]i.


Assuntos
Isquemia Encefálica/metabolismo , Encéfalo/metabolismo , Precondicionamento Isquêmico , Animais , Cálcio/metabolismo , Bloqueadores dos Canais de Cálcio/metabolismo , Maleato de Dizocilpina/metabolismo , Ácido Egtázico/análogos & derivados , Ácido Egtázico/metabolismo , Cobaias , Técnicas In Vitro , Imageamento por Ressonância Magnética , Nifedipino/metabolismo , Receptores de N-Metil-D-Aspartato
12.
J Neuropathol Exp Neurol ; 64(9): 763-9, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16141785

RESUMO

Granulocyte-colony stimulating factor (G-CSF) is reported to be neuroprotective after transient cerebral ischemia with respect to decreasing lesion volume and enhancing functional recovery. We investigated whether G-CSF is neuroprotective after permanent ischemia and the possible mechanisms underlying this neuroprotection. Mice underwent permanent or 60-minute middle cerebral artery occlusion (MCAO) and received G-CSF (50 microg/kg) or vehicle at the onset or 1 hour post-MCAO. Forty-eight hours after transient MCAO, structural magnetic resonance imaging revealed a significant reduction (50%) in the amount of edematous tissue present in G-CSF-treated mice (p < 0.05). G-CSF treatment also prevented a significant increase in ipsilateral brain water content that was present in vehicle-treated mice after transient (p < 0.05) and permanent (p < 0.001) MCAO. Forty-eight hours after permanent MCAO, G-CSF decreased (50%) the cortical lesion volume (p < 0.05). Using real-time polymerase chain reaction, we found that G-CSF treatment significantly suppressed (p < 0.05) the injury-induced upregulation of IL-1beta mRNA while having no effect on TNFalpha and NOS-2 mRNA expression. This suggests that part of the neuroprotection may be attributed to the ability of G-CSF to reduce the inflammatory response.


Assuntos
Edema Encefálico/prevenção & controle , Isquemia Encefálica/tratamento farmacológico , Encéfalo/patologia , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Interleucina-1/biossíntese , Fármacos Neuroprotetores/uso terapêutico , Animais , Encéfalo/efeitos dos fármacos , Isquemia Encefálica/patologia , Proteínas de Caenorhabditis elegans/biossíntese , Proteínas de Caenorhabditis elegans/efeitos dos fármacos , Circulação Cerebrovascular/efeitos dos fármacos , Expressão Gênica , Imageamento por Ressonância Magnética , Masculino , Camundongos , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/efeitos dos fármacos
13.
Eur J Neurosci ; 22(1): 72-8, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16029197

RESUMO

Interleukin (IL)-1beta plays an important role in the inflammatory response that results from traumatic brain injury and antagonism of the actions of this cytokine can affect outcome. We subjected male mice to aseptic cryogenic injury and assessed recovery through anatomical, histological and functional measures following treatment with recombinant mouse IL-1 receptor antagonist (IL-1ra). A single dose (1 microg, i.c.v.) at the time of injury reduced lesion volume 3 days later, as assessed by Nissl staining, and also the number (30%) of FluoroJade-positive degenerating neurones. Mice treated with IL-1ra performed better on the beam balance and in the grid test as compared with vehicle-treated animals. Furthermore, IL-1ra-treated animals showed fewer (40%) nitric oxide synthase-2-positive cells in and around the lesion. These data suggest that activation of the IL-1 receptor following trauma contributes to the pathology and that antagonism can reduce both anatomical and functional consequences of neuroinflammation.


Assuntos
Lesões Encefálicas/tratamento farmacológico , Lesões Encefálicas/metabolismo , Encéfalo/metabolismo , Óxido Nítrico Sintase/metabolismo , Receptores de Interleucina-1/antagonistas & inibidores , Sialoglicoproteínas/uso terapêutico , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Lesões Encefálicas/fisiopatologia , Contagem de Células , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Modelos Animais de Doenças , Encefalite/tratamento farmacológico , Encefalite/metabolismo , Encefalite/prevenção & controle , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Proteína Antagonista do Receptor de Interleucina 1 , Interleucina-1/antagonistas & inibidores , Interleucina-1/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Degeneração Neural/tratamento farmacológico , Degeneração Neural/metabolismo , Degeneração Neural/prevenção & controle , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/uso terapêutico , Óxido Nítrico Sintase Tipo II , Receptores de Interleucina-1/metabolismo , Resultado do Tratamento
14.
Psychopharmacology (Berl) ; 180(4): 752-60, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16001121

RESUMO

RATIONALE: Thunbergia laurifolia Linn. (TL) is an herbal medicine used to treat alcohol and drug addiction in Thai traditional medicine. A previous study demonstrated that an extract of TL increases rat striatal dopamine release in vitro. OBJECTIVES: This study determined whether a methanol extract of TL altered rat brain region activity using in vivo functional nuclear magnetic resonance imaging (fMRI) in a manner consistent with the observed effects in vitro on dopamine release. METHODS: fMRI was performed on a 2.35-T Bruker MR system. MR images were acquired from rat brain using the rapid acquisition relaxation enhanced sequence (field of view 50 mm). The imaging parameters used for the anatomical scan yielded an in-plane spatial resolution of 0.2x0.2 mm. Consecutive single-slice functional imaging over the rat brain investigated the changes in signal intensity in various parts of the brains induced by TL (200 mg/kg, i.p.) or vehicle administration. RESULTS: These demonstrate that TL increased signal intensity in various brain areas such as nucleus accumbens, globus pallidus, amygdala, frontal cortex, caudate putamen and hippocampus. These are similar to those reported previously to show effects after either cocaine or amphetamine administration. Physiological variables were not affected by the injection of TL (200 mg/kg, i.p.), but there was a small decrease in arterial blood pressure. CONCLUSIONS: The results indicate that TL increases significant neuronal activity in specific brain regions responsible for reward and locomotor behaviour (fixed-effect analysis); however, there is no significant difference between TL and vehicle-treated groups with random-effect analysis (population statistic). The active compound(s) in TL responsible for the pharmacological effects of TL remain to be identified.


Assuntos
Acanthaceae/química , Encéfalo/efeitos dos fármacos , Imageamento por Ressonância Magnética , Extratos Vegetais/farmacologia , Análise de Variância , Animais , Gasometria/métodos , Pressão Sanguínea/efeitos dos fármacos , Encéfalo/anatomia & histologia , Encéfalo/irrigação sanguínea , Mapeamento Encefálico , Circulação Cerebrovascular/efeitos dos fármacos , Lateralidade Funcional , Processamento de Imagem Assistida por Computador/métodos , Oxigênio/sangue , Ratos , Fatores de Tempo
15.
Exp Neurol ; 193(2): 522-30, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15869954

RESUMO

Gender differences in outcome following cerebral ischemia have frequently been observed and attributed to the actions of steroid hormones. Progesterone has been shown to possess neuroprotective properties following transient ischemia, with respect to decreasing lesion volume and improving functional recovery. The present study was designed to determine the mechanisms of progesterone neuroprotection, and whether these relate to the inflammatory response. Male mice underwent either 60 min or permanent middle cerebral artery occlusion (MCAO) and received progesterone (8 mg/kg ip) or vehicle 1 h, 6 h and 24 h post-MCAO. Forty-eight hours following transient MCAO, structural magnetic resonance imaging revealed a significant decrease in the amount of edematous tissue present in progesterone-treated mice as compared with vehicle. Using real-time PCR we found that progesterone treatment significantly suppressed the injury-induced upregulation of interleukin (IL)-1beta, transforming growth factor (TGF)beta2, and nitric oxide synthase (NOS)-2 mRNAs in the ipsilateral hemisphere while having no effect on tumor necrosis factor (TNF)-alpha mRNA expression. Progesterone treatment following permanent MCAO also resulted in a significant decrease in lesion volume. This was not apparent in mice lacking a functional NOS-2 gene. Thus, progesterone is neuroprotective in both permanent and transient ischemia, and this effect is related to the suppression of specific aspects of the inflammatory response.


Assuntos
Isquemia Encefálica/enzimologia , Inflamação/prevenção & controle , Óxido Nítrico Sintase/metabolismo , Progesterona/uso terapêutico , Animais , Encéfalo/patologia , Isquemia Encefálica/complicações , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média/complicações , Inflamação/etiologia , Interleucina-1/genética , Interleucina-1/metabolismo , Imageamento por Ressonância Magnética/métodos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase Tipo II , Progesterona/administração & dosagem , RNA Mensageiro/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Sais de Tetrazólio , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
16.
Psychopharmacology (Berl) ; 180(4): 716-23, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15864553

RESUMO

RATIONALE: The psychomotor stimulant methylphenidate is used in the treatment of attention deficit hyperactivity disorder (ADHD). Whereas the mechanism is not fully understood it is suggested to involve restoration of impaired dopamine function found in ADHD. OBJECTIVES: The aim of this study was to determine the effects of methylphenidate on brain region activation in vivo using pharmacological magnetic resonance imaging (phMRI) in a potential rat model of ADHD. METHODS: Rats were treated bi-daily [from postnatal day (PND) 24] for 4 days with the dopamine re-uptake inhibitor GBR 12909 (30 mg/kg i.p) or vehicle (control). On PND 57 rats were administered methylphenidate (4 mg/kg i.p) and locomotor activity measured. In a separate group of animals, blood oxygen level dependent (BOLD) response was measured using phMRI to determine changes in brain region activation produced by methylphenidate (4 mg/kg i.p.) in GBR 12909-pretreated or control rats. RESULTS: Methylphenidate produced a greater locomotor-stimulant response in controls compared with GBR 12909 rats. Pretreatment with GBR 12909 reduced the BOLD response produced by methylphenidate compared with that in control animals. The main effects of methylphenidate on the BOLD response were seen in the caudate, frontal cortex, hippocampus and hypothalamus. CONCLUSIONS: Short-term treatment with GBR 12909 in young rats causes long-term changes in dopaminergic systems, altering the methylphenidate-induced behavioural response and brain region activation compared with that in vehicle-pretreated rats. The results further support the view that altered dopaminergic function may be an important factor in ADHD and the value of animal models with this functional neurochemical deficit.


Assuntos
Transtornos de Deficit da Atenção e do Comportamento Disruptivo/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Inibidores da Captação de Dopamina/farmacologia , Metilfenidato/farmacologia , Análise de Variância , Animais , Animais Recém-Nascidos , Encéfalo/irrigação sanguínea , Mapeamento Encefálico , Modelos Animais de Doenças , Inibidores da Captação de Dopamina/uso terapêutico , Interações Medicamentosas , Imageamento por Ressonância Magnética/métodos , Masculino , Metilfenidato/uso terapêutico , Oxigênio/sangue , Piperazinas/farmacologia , Ratos , Fatores de Tempo
17.
Eur J Neurosci ; 21(6): 1547-54, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15845082

RESUMO

Previous studies suggest that progesterone may possess neuroprotective properties after traumatic insult but, with the exception of reduced formation of cerebral oedema, limited experimental evidence has been presented to support this claim. In the present study we focused on the effect of progesterone treatment on structural and functional deficits in an experimental model of traumatic brain injury. Female mice exhibited significantly (P = 0.0445) reduced lesion volumes compared with males after aseptic cryogenic cerebral injury (ACI), suggesting that female sex steroids provide protection against this injury. In male mice, progesterone treatment after injury (three intraperitoneal doses of 8 mg/kg) reduced lesion volume (P = 0.0429) and improved performance in a spatial cognitive task (Morris water maze; P = 0.0014). However, progesterone had no demonstrable effect on the formation of oedema as measured using T2-weighted magnetic resonance imaging, nor did it affect brain water content. The pro-inflammatory cytokines TNF-alpha and IL-1beta, and growth factors BDNF and G-CSF, were all strongly transcriptionally activated after ACI. However, progesterone administration did not affect expression of these genes. This study provides strong evidence that progesterone possesses neuroprotective properties in a mouse model of traumatic brain injury, but suggests that the steroid achieves this effect through mechanism(s) independent of the inflammatory response or growth factor up-regulation.


Assuntos
Lesões Encefálicas/prevenção & controle , Substâncias de Crescimento/biossíntese , Fármacos Neuroprotetores/uso terapêutico , Progesterona/uso terapêutico , Animais , Edema Encefálico/tratamento farmacológico , Edema Encefálico/metabolismo , Edema Encefálico/prevenção & controle , Lesões Encefálicas/tratamento farmacológico , Lesões Encefálicas/metabolismo , Feminino , Regulação da Expressão Gênica/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores/farmacologia , Progesterona/farmacologia , Fatores de Tempo
18.
Glia ; 45(4): 325-37, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-14966864

RESUMO

Blood-brain barrier (BBB) breakdown is a feature of cerebral ischaemia, multiple sclerosis, and other neurodegenerative diseases, yet the relationship between astrocytes and the BBB integrity remains unclear. We present a simple in vivo model in which primary astrocyte loss is followed by microvascular damage, using the metabolic toxin 3-chloropropanediol (S-alpha-chlorohydrin). This model is uncomplicated by trauma, ischaemia, or primary immune involvement, permitting the study of the role of astrocytes in vascular endothelium integrity, maintenance of the BBB, and neuronal function. Male Fisher F344 rats given 3-chloropropanediol show astrocytic damage and death at 4-24 h in symmetrical brainstem and midbrain nuclear lesions, while neurons show morphological changes at 24-48 h. Fluorescent 10 kDa dextran tracers show the BBB leaking from 24 h, progressing to petechial haemorrhage after 48-72 h, with apparent repair after 6 days. BBB breakdown, but not the earlier astrocytic death, is accompanied by a delayed increase in blood flow in the inferior colliculus. An ED1 inflammatory response develops well after astrocyte loss, suggesting that inflammation may not be a factor in starting BBB breakdown. This model demonstrates that the BBB can self-repair despite the apparent absence of direct astrocytic-endothelial contact. The temporal separation of pathological events allows pharmacological intervention, and the mild reversible ataxia permits long-term survival studies of repair mechanisms.


Assuntos
Astrócitos/patologia , Barreira Hematoencefálica/patologia , Tronco Encefálico/irrigação sanguínea , Tronco Encefálico/patologia , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/ultraestrutura , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/ultraestrutura , Tronco Encefálico/efeitos dos fármacos , Tronco Encefálico/ultraestrutura , Contagem de Células/métodos , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Circulação Cerebrovascular/efeitos dos fármacos , Circulação Cerebrovascular/fisiologia , Masculino , Microcirculação/efeitos dos fármacos , Microcirculação/patologia , Microcirculação/ultraestrutura , Ratos , Ratos Endogâmicos F344 , alfa-Cloridrina/toxicidade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...