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Microdialysis study of striatal dopamine in MPTP-hemilesioned rats challenged with apomorphine and amphetamine

DOMBROWSKI, Patricia Andreia; CARVALHO, Milene Cristina; MIYOSHI, Edmar; CORREIA, Diego; BORTOLANZA, Mariza; SANTOS, Lucelia Mendes dos; WIETZIKOSKI, Evellyn Claudia; ECKART, Moritz Thede; SCHWARTING, Rainer K. W.; BRANDAO, Marcus Lira; CUNHA, Claudio Da
Fonte: ELSEVIER SCIENCE BV Publicador: ELSEVIER SCIENCE BV
Tipo: Artigo de Revista Científica
Português
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Motor impairments of Parkinson`s disease (PD) appear only after the loss of more than 70% of the DAergic neurons of the substantia nigra pars compacta (SNc). An earlier phase of this disease can be modeled in rats that received a unilateral infusion of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) into the SNc. Though these animals do not present gross motor impairments, they rotate towards the lesioned side when challenged with DAergic drugs, like amphetamine and apomorphine. The present study aimed to test whether these effects occur because the drugs disrupt compensatory mechanisms that keep extracellular levels of dopamine in the striatum (DA(E)) unchanged. This hypothesis was tested by an in vivo microdialysis study in awake rats with two probes implanted in the right and left striatum. Undrugged rats did not present turning behaviour and their basal DA(E) did not differ between the lesioned and sham-lesioned sides. However, after apomorphine treatment, DA(E) decreased in both sides, but to a larger extent in the lesioned side at the time the animals started ipsiversive turning behaviour. After amphetamine challenge, DA(E) increased in both sides, becoming significantly higher in the non-lesioned side at the time the animals started ipsiversive turning behaviour. These results are in agreement with the hypothesis that absence of gross motor impairments in this rat model of early phase PD depends on maintenance of extracellular DA by mechanisms that may be disrupted by events demanding its alteration to higher or lower levels. (C) 2010 Elsevier B.V. All rights reserved.; CNPq; CAPES

Extracellular serotonin level in the basolateral nucleus of the amygdala and dorsal periaqueductal gray under unconditioned and conditioned fear states: An in vivo microdialysis study

ZANOVELI, Janaina M.; CARVALHO, Milene C.; CUNHA, Joice M.; BRANDAO, Marcus L.
Fonte: ELSEVIER SCIENCE BV Publicador: ELSEVIER SCIENCE BV
Tipo: Artigo de Revista Científica
Português
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36.93%
Serotonin (5-HT) plays a key role in the neural circuitry mediating unconditioned and conditioned fear responses related to panic and generalized anxiety disorders. The basolateral nucleus of the amygdala (BLA) and the dorsal periaqueductal gray (dPAG) appear to be mainly involved in these conditions. The aim of this study was to measure the extracellular level of 5-HT and its metabolite 5-hydroxyindolacetic acid (5-HIAA) in the BLA and dPAG during unconditioned and conditioned fear states using in vivo microdialysis procedure. Thus, for the unconditioned fear test, animals were chemically stimulated in the dPAG with semicarbazide, an inhibitor of the gamma-aminobutyric acid-synthesizing enzyme glutamic acid decarboxylase. For the conditioned fear test, animals were subjected to a contextual conditioned fear paradigm using electrical footshock as the unconditioned stimulus. The results show that the 5-HT and 5-HIAA level in the BLA and dPAG did not change during unconditioned fear, whereas 5-HT concentration, but not 5-HIAA concentration, increased in these brain areas during conditioned fear. The present study showed that the 5-HT system was activated during conditioned fear, whereas it remained unchanged during unconditioned fear...

Perfil diário e os mecanismos de produção de melatonina pela glândula pineal de ratos diabéticos por estreptozotocina.; Pineal melatonin production in Streptozotocin-diabetic rats: mechanisms and microdialysis daily profile.

Amaral, Fernanda Gaspar do
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 27/10/2009 Português
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A pineal participa da sincronização do organismo pela síntese de melatonina. Diabetes é um distúrbio metabólico caracterizado por hiperglicemia. Diante da controvérsia sobre a síntese de melatonina em animais diabéticos, esse trabalho objetivou avaliar as alterações da glândula pineal mediante o diabetes induzido por STZ (60mg/kg, i.p.). Ratos wistar (250-280g, 12h/12h claro/escuro) foram utilizados em todos os procedimentos que envolveram técnicas de FACS, microdiálise, HPLC, radiometria da atividade enzimática e qPCR. Os resultados mostraram que o diabetes causa diminuição (50%) e perda do perfil mono/bifásico da síntese pineal de melatonina, que não é causada por necrose ou apoptose dos pinealócitos e reflete um desarranjo no metabolismo pineal, evidenciado pela diminuição na atividade da AANAT (55%). Observou-se também um desbalanço rítmico de fatores determinantes como a expressão do receptor ß1 e a atividade e expressão das enzimas TPH1 e HIOMT. A menor concentração de melatonina circulante pode ser um fator contribuinte para o desenvolvimento da doença.; The gland is involved in the organism synchronization via its hormone melatonin. Diabetes involves hyperglicemia and insulin synthesis/signaling impairment. The aim of this work was to evaluate the pineal melatonin synthesis in STZ-diabetic rats (60mg/kg...

Avaliação do efeito de um extrato lipofílico de Hypericum caprifoliatum Cham.& Schltdl sobre os níveis cerebrais de dopamina e seus metabólitos através de microdiálise cerebral em ratos conscientes; Evaluation of the effect of Hypericum caprifoliatum Cham. & Schltdl lipophilic extract on the extracellular levels of dopamine and its metabolites by cerebral microdialysis in freely moving rats

Munari, Leonardo Mattos
Fonte: Universidade Federal do Rio Grande do Sul Publicador: Universidade Federal do Rio Grande do Sul
Tipo: Dissertação Formato: application/pdf
Português
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OBJETIVO: Desenvolver e validar a técnica de CLAE-DE para o doseamento de dopamina (DA), ácido diidrofenilacético (DOPAC), ácido homovanílico (HVA) e 3-metoxitiramina (3-MT); validar a técnica de microdiálise (MD) cerebral em animais conscientes e avaliar o efeito do tratamento agudo com um extrato lipofílico das partes aéreas de Hypericum caprifoliatum (HCP) sobre os níveis cerebrais de DA e seus metabólitos. MATERIAIS E MÉTODOS: A validação analítica foi realizada conforme o preconizado pela ANVISA, com análise dos parâmetros linearidade, precisão, exatidão, especificidade e limite inferior de quantificação. A técnica de microdiálise foi realizada de forma clássica: guias de sonda foram implantadas nas regiões cerebrais de interesse por cirurgia estereotáxica; os dialisados foram obtidos, 48 horas após a cirurgia, através da perfusão da sonda com líquido cérebroespinhal artificial (1 μL/min) e coleta durante três horas, em intervalos de 20 min; as três primeiras coletas foram utilizadas para determinação da linha de base e só então foram administrados os tratamentos. Para a validação da MD a sonda foi implantada no estriado (A: -0,3; L: + 3,2; P: - 4,5) e o tratamento foi sulfato de anfetamina (2 mg/kg...

A brain microdialysis study on 5-HT release in freely moving rat lines selectively bred for differential 5-HT1A receptor function

Gonzalez,L.E.; Parada,M.A.; Tucci,S.; Teneud,L.; Overstreet,D.H.; Hernandez,L.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/02/2003 Português
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Breeding for high and low hypothermic responses to systemic administration of a serotonin1A (5-HT1A) receptor agonist (8-hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT) has resulted in high DPAT-sensitive (HDS) and low DPAT-sensitive (LDS) lines of rats, respectively. These lines also differ in several behavioral measures associated with stress. In the present microdialysis study we observed that basal 5-HT concentrations in the prefrontal cortex and dorsal hippocampus did not differ significantly between HDS and LDS rats. Thus, behavioral differences between the HDS and LDS lines might not be attributed to differences in basal 5-HT release. However, both lines had lower basal levels of 5-HT release than their randomly bred control group (random DPAT-sensitive, RDS) in the prefrontal cortex (mean ± SEM, pg/20 µl, was 3.0 ± 0.4 for LDS, 3.8 ± 0.3 for HDS and 6.4 ± 0.6 for RDS; F(2,59) = 5.8, P<0.005). The administration of (±)-fenfluramine (10 mg/kg) induced a greater increase in hippocampal 5-HT levels in HDS rats (500%) as compared with LDS (248%) or RDS (243%) rats (P<0.0001). There were no significant differences in the prefrontal cortex among lines, with a fenfluramine-induced 5-HT increase of about 900% in the three groups. This differential response to fenfluramine may be due to functional alterations of hippocampal 5-HT reuptake sites in the HDS line.

Prediction of microdialysis relative recovery of flavone derivatives based on molecular descriptors

Zhan,Shuyu; Huang,Jianping; Shao,Qing; Fan,Xiaohui; Guo,Wenjing
Fonte: Sociedade Brasileira de Química Publicador: Sociedade Brasileira de Química
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/11/2012 Português
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Relative recovery (Re) is one of the major concerns of microdialysis, a valuable sampling technique which can continuously collect unbound drugs in blood and most tissues. For a given microdialysis probe, the recovery of every compound from the probe is related to its structural characteristics and physicochemical property if the experiment condition is fixed. In this work, quantitative structure-property relationship (QSPR) models using multiple linear regression (MLR) and support vector machine (SVM) methods were setup to excavate the relationships of microdialysis Re of compounds and their molecular descriptors which capture the structural characteristics of molecules for a series of flavone derivatives. As result, significant statistical parameters (MLR model: R² = 0.9268 (correlation coefficient), Q²LOO = 0.8572 (explained variance in prediction) and Q²ext = 0.8639 (external explained variance), and SVM model: R² = 0.9383 and Q²ext = 0.8536) were obtained, indicating good stability and predictive ability of the models. Therefore, it seems feasible to predict the microdialysis relative recovery of some compounds from their molecular descriptors. This investigation was an innovative trial and can provide new methods for researching the microdialysis recovery of the compounds.

Intracerebral microdialysis combined with recording of extracellular field potential: a novel method for investigation of depolarizing drugs in vivo.

Obrenovitch, T P; Urenjak, J; Zilkha, E
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /12/1994 Português
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1. The purpose of this study was to examine whether depolarizations evoked by excitatory amino acids can be recorded quantitatively, in vivo, with a microelectrode incorporated within a microdialysis probe. 2. Microdialysis probes incorporating a chlorided silver wire were implanted in the striatum of anaesthetized rats and perfused with artificial cerebrospinal fluid (ACSF). Increasing concentrations of excitatory amino acids were applied for 2 min via the microdialysis probe, and the extracellular direct current (d.c.) potential was recorded between the microdialysis electrode and a reference electrode placed under the scalp. 3. N-methyl-D-aspartate (NMDA, 25-500 microM), alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA, 5-1000 microM), kainate (5-500 microM), and glutamate (0.25-100 mM) evoked concentration-dependent depolarizations with maxima ranging from 7 to 10 mV, i.e. 3 to 10 times larger than those recorded from brain slices in vitro. Depolarizations evoked by glutamate receptor agonists applied by microdialysis shared several features with those recorded from brain slices. The most characteristic were: steep onset and recovery of NMDA and glutamate responses; marked post-depolarization hyperpolarization with NMDA; and very slow recovery after kainate application. At high concentrations (500 microM)...

Cochlear Microdialysis for Quantification of Dexamethasone and Fluorescein Entry into Scala Tympani During Round Window Administration

Hahn, Hartmut; Kammerer, Bernd; DiMauro, Andre; Salt, Alec N.; Plontke, Stefan K.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
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Before new drugs for the treatment of inner ear disorders can be studied in controlled clinical trials, it is important that their pharmacokinetics be established in inner ear fluids. Microdialysis allows drug levels to be measured in perilymph without the volume disturbances and potential cerebrospinal fluid contamination associated with fluid sampling. The aims of this study were to show: (i) that despite low recovery rates from miniature dialysis probes, significant amounts of drug are removed from small fluid compartments, (ii) that dialysis sampling artifacts can be accounted for using computer simulations and (iii) that microdialysis allows quantification of the entry rates through the round window membrane (RWM) into scala tympani (ST). Initial experiments used microdialysis probes in small compartments in vitro containing sodium fluorescein. Stable concentrations were observed in large compartments (1000 μl) but significant concentration declines were observed in smaller compartments (100, 10 and 5.6 μl) comparable to the size of the inner ear. Computer simulations of these experiments closely approximated the experimental data. In in vivo experiments, sodium fluorescein 10 mg/ml and dexamethasone-dihydrogen-phosphate disodium salt 8 mg/ml were simultaneously applied to the RWM of guinea pigs. Perilymph concentration in the basal turn of ST was monitored using microdialysis. The fluorescein concentration reached after 200 min application (585 ± 527 μg/ml) was approximately twice that of dexamethasone phosphate (291 ± 369 μg/ml). Substantial variation in concentrations was found between animals by approximately a factor of 34 for fluorescein and at least 41 for dexamethasone phosphate. This is...

Coupling Microdialysis Sampling to Microchip Electrophoresis in a Reversibly Sealed Device

Mecker, Laura C.; Martin, R. Scott
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /10/2007 Português
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In this paper, we describe the fabrication and characterization of a reversibly sealed microchip device that is used to couple microdialysis sampling to microchip electrophoresis. The ability to interface microdialysis sampling and microchip electrophoresis in a device that is amenable to reversible sealing is advantageous from a repeated use standpoint. Commercially available tubing coming from the microdialysis probe is directly inserted into the chip and flow from the probe is interfaced to the electrophoresis portion of the device through integrated pneumatic valves. Fluorescence detection was used to characterize the poly(dimethylsiloxane)-based device in terms of injection reproducibility. It was found that the entire system (microdialysis probe and microchip device) has a concentration response lag time of 170 sec. Microdialysis sampling followed by an electrophoretic separation of amino acids derivatized with naphthalene-2,3-dicarboxaldehyde/cyanide was also demonstrated.

Microdialysis of dopamine interpreted with quantitative model incorporating probe implantation trauma

Bungay, Peter M.; Newton-Vinson, Paige; Isele, Wanda; Garris, Paul A.; Justice, Joseph B.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /08/2003 Português
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Although microdialysis is widely used to sample endogenous and exogenous substances in vivo, interpretation of the results obtained by this technique remains controversial. The goal of the present study was to examine recent criticism of microdialysis in the specific case of dopamine (DA) measurements in the brain extracellular microenvironment. The apparent steady-state basal extracellular concentration and extraction fraction of DA were determined in anesthetized rat striatum by the concentration difference (no-net-flux) micro-dialysis technique. A rate constant for extracellular clearance of DA calculated from the extraction fraction was smaller than the previously determined estimate by fast-scan cyclic voltammetry for cellular uptake of DA. Because the relatively small size of the voltammetric microsensor produces little tissue damage, the discrepancy between the uptake rate constants may be a consequence of trauma from microdialysis probe implantation. The trauma layer has previously been identified by histology and proposed to distort measurements of extracellular DA levels by the no-net-flux method. To address this issue, an existing quantitative mathematical model for microdialysis was modified to incorporate a traumatized tissue layer interposed between the probe and surrounding normal tissue. The tissue layers are hypothesized to differ in their rates of neurotransmitter release and uptake. A post-implantation traumatized layer with reduced uptake and no release can reconcile the discrepancy between DA uptake measured by microdialysis and voltammetry. The model predicts that this trauma layer would cause the DA extraction fraction obtained from microdialysis in vivo calibration techniques...

The development of multiple probe microdialysis sampling in the stomach

Woo, Kristin L.; Lunte, Craig E.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
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A multiple probe approach of implanting microdialysis probes into each separate tissue layer would better represent sampling from the stomach. Presently, microdialysis sampling experiments are performed with only a single probe in the submucosa to represent sampling from the stomach tissue. The focus of this research was to develop a four-probe microdialysis sampling design to simultaneously monitor the stomach lumen, mucosa, submucosa and in the blood of the rat. Due to the small outer diameter of the microdialysis probe (350 μm), implantation into each separate layer was achieved with confirmation of probe location from histological examination. To assess the significance of sampling by this approach, multiple probe microdialysis sampling was used to monitor drug absorption in the stomach. Salicylic acid, caffeine and metoprolol were individually dosed to the ligated stomach. Analysis of the dialysate samples was performed by HPLC–UV and concentration–time curves and pharmacokinetics analysis were used to determine differences between the different probe locations.

COMBINING MICRODIALYSIS, NANOLC-MS, AND MALDI-TOF/TOF TO DETECT NEUROPEPTIDES SECRETED IN THE CRAB, CANCER BOREALIS

Behrens, Heidi L.; Chen, Ruibing; Li, Lingjun
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
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Microdialysis is a useful technique for sampling neuropeptides in vivo and decapod crustaceans are important model organisms for studying how these peptides regulate physiological processes. However, to date no microdialysis procedure has been reported for sampling neuropeptides from crustaceans. Here we report the first application of microdialysis to sample neuropeptides from the hemolymph of the crab, Cancer borealis. Microdialysis probes were implanted into the pericardial region of live crabs and the resulting dialysates were desalted, concentrated, and analyzed by LC-ESI-QTOF and MALDI-TOF/TOF mass spectrometry. Analysis of in vitro microdialysates of hemolymph revealed more neuropeptides and fewer protein fragments than hemolymph prepared by typical analysis methods. Mass spectra of in vivo dialysates displayed neuropeptides from ten peptide families, including the RFamide, allatostatin, and orcokinin families. In addition, GAHKNYLRFa, SDRNFLRFa, and TNRNFLRFa were sequenced from hemolymph dialysates. The detection of these neuropeptides in the hemolymph suggests that they are functioning as hormones as well as neuromodulators. In vivo microdialysis offers the capability to further study these and other neuropeptides in crustacean hemolymph...

Affinity-based microdialysis sampling using heparin for in vitro collection of human cytokines

Wang, Yuexi; Stenken, Julie A.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
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27.35%
Microdialysis sampling is a widely used method to sample from complex biological matrices. Cytokines are important signaling proteins that are typically recovered with low relative recovery values during microdialysis sampling. Heparin was included in the microdialysis perfusion fluid as an affinity agent to increase in vitro recovery of different cytokines through polyethersulfone (PES) microdialysis membranes with 100 kDa molecular weight cutoff. No change in fluid volumes collected from the microdialysis probes occurred when heparin was included in the perfusion fluid up to concentrations of 10 μM. The loss of heparin (10 μM) across the dialysis membrane was minimal (2.7±0.9%, n=3). Additionally, heparin at these concentrations did not interfere with the cytokine immunoassays. The control and heparin-enhanced relative recoveries for five human cytokines using 0.1 μM heparin in the microdialysis perfusion fluid flowing at 0.5 μL min−1 were (n=3): interleukin-4 (IL-4), 4.2 ± 0.5% and 7.2±3.1%; interleukin-6 (IL-6), 1.4±0.8% and 3.6±1.3%; interleukin-7 (IL-7), 1.3±0.8% and 4.8±1.8%; monocyte chemoattractant protein-1 (MCP-1), 9.0±1.6% and 19.5±2.7%; and tumor necrosis factor-α (TNF-α), 7.4±1.3% and 16.9±1.6%, respectively. Heparin increased the microdialysis sampling relative recovery of several human cytokines in vitro.

Pilot Investigation on Long-Term Subcutaneous Microdialysis: Proof of Principle in Humans

Simmel, Franziska; Kirbs, Claudia; Erdogan, Zeynep; Lackner, Edith; Zeitlinger, Markus; Kloft, Charlotte
Fonte: Springer US Publicador: Springer US
Tipo: Artigo de Revista Científica
Publicado em 13/10/2012 Português
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27.42%
Reliable drug concentration measurements at the target site are increasingly demanded and can be achieved by microdialysis. The aim of this pilot study was to demonstrate the proof of principle of long-term subcutaneous microdialysis in humans. For long-term microdialysis, a special setting implementing both concentric and linear catheters has been developed ensuring good clinical practice compliance, tolerability, and convenience for participants and personnel. As a model compound, moderately lipophilic voriconazole was selected as a well-characterized drug in in vitro microdialysis experiments. Multiple in vivo relative recovery (RR) determinations for microdialysis were performed by retrodialysis during the entire study (n = 48 samples). Continuous microdialysis was successfully applied and well tolerated over 87 h in three adults for the first time. RR revealed low intra-individual (coefficient of variation (CV) = 4.4–12.5%) and inter-individual variability (CV = 4.3–12.5%) across all samples and catheters. Lower RR values were consistently determined for linear catheters. One catheter leakage was managed without an impact on the reliability of the RR values. Overall, RR values were calculated to be 73.3% (linear: CV = 18.5%...

Cerebral microdialysis in clinical studies of drugs: pharmacokinetic applications

Shannon, Richard J.; Carpenter, Keri L. H.; Guilfoyle, Mathew R.; Helmy, Adel; Hutchinson, Peter J.
Fonte: Springer US Publicador: Springer US
Tipo: Artigo de Revista Científica
Português
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The ability to deliver drug molecules effectively across the blood–brain barrier into the brain is important in the development of central nervous system (CNS) therapies. Cerebral microdialysis is the only existing technique for sampling molecules from the brain extracellular fluid (ECF; also termed interstitial fluid), the compartment to which the astrocytes and neurones are directly exposed. Plasma levels of drugs are often poor predictors of CNS activity. While cerebrospinal fluid (CSF) levels of drugs are often used as evidence of delivery of drug to brain, the CSF is a different compartment to the ECF. The continuous nature of microdialysis sampling of the ECF is ideal for pharmacokinetic (PK) studies, and can give valuable PK information of variations with time in drug concentrations of brain ECF versus plasma. The microdialysis technique needs careful calibration for relative recovery (extraction efficiency) of the drug if absolute quantification is required. Besides the drug, other molecules can be analysed in the microdialysates for information on downstream targets and/or energy metabolism in the brain. Cerebral microdialysis is an invasive technique, so is only useable in patients requiring neurocritical care, neurosurgery or brain biopsy. Application of results to wider patient populations...

Model for Concomitant Microdialysis Sampling of the Pons and Cerebral Cortex in Rhesus Macaques (Macaca mulatta)

McCully, Cynthia M; Pastakia, Devang; Bacher, John; Thomas, Marvin L; Steffen-Smith, Emilie A; Saleem, Kadharbatcha; Murphy, Robert F; Walbridge, Stuart; Brinster, Lauren; Widemann, Brigitte C; Warren, Katherine E
Fonte: American Association for Laboratory Animal Science Publicador: American Association for Laboratory Animal Science
Tipo: Artigo de Revista Científica
Português
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Pediatric diffuse intrinsic pontine gliomas are aggressive brainstem tumors that fail to respond to treatment. We hypothesize that the protective features of the pons may hinder chemotherapeutic agents from entering pontine tissue compared with cortical brain tissue. To test this hypothesis, we developed a unique nonhuman primate model using microdialysis, a continuous in vivo extracellular sampling technique, to compare drug exposure concurrently in pontine tissue, cortical tissue, CSF, and plasma after intravenous administration of chemotherapeutic agents. The surgical coordinates and approach for microdialysis cannula–probe placement were determined in 5 adult male rhesus monkeys (Macaca mulatta) by using MRI. Microdialysis cannulas–probes were implanted stereotactically in the brain, retrodialysis was performed to measure relative recovery, and a 1-h intravenous infusion of temozolomide was administered. Continuous microdialysis samples were collected from the pons and cortex over 4 h with concurrent serial plasma and CSF samples. Postsurgical verification of microdialysis cannula–probe placement was obtained via MRI in 3 macaques and by gross pathology in all 5 animals. The MRI-determined coordinates and surgical methodologies resulted in accurate microdialysis probe placement in the pons and cortex in 4 of the 5 macaques. Histologic examination from these 4 animals revealed negligible tissue damage to the pontine and cortical tissue from microdialysis. One macaque was maintained for 8 wk and had no deficits attributed to the procedure. This animal model allows for the determination of differences in CNS penetration of chemotherapeutic agents in the pons...

Pharmacological Mitigation of Tissue Damage During Brain Microdialysis

Nesbitt, Kathryn M.; Jaquins-Gerstl, Andrea; Skoda, Erin M.; Wipf, Peter; Michael, Adrian C.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
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Microdialysis sampling in the brain is employed frequently in the chemical analysis of neurological function and disease. But, implanting the probes, which are substantially larger than the size and spacing of brain cells and blood vessels, is injurious and triggers ischemia, gliosis, and cell death at the sampling site. The nature of the interface between the brain and the microdialysis probe is critical to the use of microdialysis as a neurochemical analysis technique. The objective of the work reported here was to investigate the potential of two compounds, dexamethasone, a glucocorticoid anti-inflammatory agent, and XJB-5-131, a mitochondrially-targeted reactive oxygen species scavenger, to mitigate the penetration injury. Measurements were performed in the rat brain striatum, which is densely innervated by axons that release dopamine, an electroactive neurotransmitter. We used voltammetry to measure electrically evoked dopamine release next to microdialysis probes during the retrodialysis of dexamethasone or XJB-5-131. After the in vivo measurements, the brain tissue containing the microdialysis probe tracks was examined by fluorescence microscopy using markers for ischemia, neuronal nuclei, macrophages, and dopamine axons and terminals. Dexamethasone and XJB-5-131 each diminished the loss of evoked dopamine activity...

The use of combined telemetry and microdialysis techniques to assess 3,4- methylenedioxymethamphetamine (MDMA, ‘Ecstasy’) effects in rats.

Omar, Intan Sofia
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Tese de Doutorado
Publicado em //2015 Português
Relevância na Pesquisa
37.18%
3,4-methylenedioxymethamphetamine (MDMA, ‘Ecstasy’) is known to produce hyperthermia and adverse cardiovascular effects in humans following consumption, which can be life threatening. In animals, MDMA also produces similar effects as seen in humans such as increase in core body temperature (Tc) which has been linked to chronic neurotoxicity. Currently, clinical treatment of these adverse effects is inadequate mainly due to limited understanding of the mechanism involved in the acute MDMA-induced adverse effects. Due to ethical reasons, MDMA studies in humans are limited and studies have relied on the use of animal models to investigate MDMA effects. Therefore, it is important to assess MDMA-induced effects using appropriate techniques to relate the findings from animals to humans. The general aims of this thesis were to investigate effects of different methods used to measure core body temperature and behaviour following MDMA administration and the validity of combined telemetry and microdialysis techniques to assess MDMA and its active metabolite, 3,4-methylenedioxyamphetamine (MDA) effects on body temperature (Tc), behaviour, heart rate (HR), locomotor activity (LMA), and 5-HT extracellular levels in the rat striatum. The first part of this thesis looked at the influence of methodological approaches used to assess changes in core body temperature and behaviour following MDMA administration. A number of studies used rectal probe measurement which requires handling and restraining of rats which results in confounding effects on the parameters measured including Tc and behaviour. Telemetry has been developed to measure these behavioural parameters without the necessity of handling the rats. The use of rectal probe caused potentiation of 10mg/kg (i.p.) MDMA-induced increase in core body temperature compared to the use of telemetry to measure Tc during the first 60 minutes following MDMA administration and has also resulted in a lower survival rate. These results demonstrate the importance of using appropriate techniques when measuring these parameters to avoid confounding effects and that telemetry provides a more accurate assessment of MDMA-induced change in core body temperature. The second part of the thesis looked at the validity of combined telemetry and microdialysis techniques to investigate effects of systemic administration of MDMA and central administration of MDMA and MDA on Tc...

Consensus statement from the 2014 International Microdialysis Forum 8

Hutchinson, Peter; Jalloh, Ibrahim; Helmy, Adel; Carpenter, Keri L.; Rostami, Elham; Bellander, Bo-Michael; Boutelle, Martyn G.; Chen, Jeff W.; Claassen, Jan; Dahyot-Fizelier, Claire; Enblad, Per; Gallagher, Clare N.; Helbok, Raimund; Hillered, Lars; Le R
Fonte: Department of Clinical Neuroscience, University of Cambridge Publicador: Department of Clinical Neuroscience, University of Cambridge
Tipo: Article; published version
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This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00134-015-3930-y; Microdialysis enables the chemistry of the extracellular interstitial space to be measured. Use of this technique in patients with acute brain injury has increased our understanding of the pathophysiology of several acute neurological disorders. In 2004 a consensus document on the clinical application of cerebral microdialysis was published. Since then there have been significant advances in the clinical use of microdialysis in neurocritical care. The objective of this review is to report on the International Microdialysis Forum held in Cambridge, UK, in April 2014 and to produce a revised and updated consensus statement about its clinical use including technique, data interpretation, relationship with outcome, role in guiding therapy in neurocritical care and research applications.; We gratefully acknowledge financial support for participants as follows: P.J.H. - National Institute for Health Research (NIHR) Professorship and the NIHR Biomedical Research Centre, Cambridge; I.J. ? Medical Research Council (G1002277 ID 98489); A. H. - Medical Research Council, Royal College of Surgeons of England; K.L.H.C. - NIHR Biomedical Research Centre...

Matrix Metalloproteinase Expression in Contusional Traumatic Brain Injury: A Paired Microdialysis Study

Guilfoyle, Matthew R.; Carpenter, Keri L. H.; Helmy, Adel; Pickard, John D.; Menon, David K.; Hutchinson, Peter J. A.
Fonte: Mary Ann Liebert Publicador: Mary Ann Liebert
Tipo: Article; published version
Português
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This is the final published version. It was first made available by Mary Ann Liebert at http://dx.doi.org/10.1089/neu.2014.3764; Matrix metalloproteinases (MMPs) are extracellular enzymes that have been implicated in the pathophysiology of blood? brain barrier (BBB) breakdown, contusion expansion, and vasogenic edema after traumatic brain injury (TBI). Specifically, in focal injury models, increased MMP-9 expression has been observed in pericontusional brain, and MMP-9 inhibitors reduce brain swelling and final lesion volume. The aim of this study was to examine whether there is a similarly localized increase of MMP concentrations in patients with contusional TBI. Paired microdialysis catheters were inserted into 12 patients with contusional TBI (with or without associated mass lesion) targeting pericontusional and radiologically normal brain defined on admission computed tomography scan. Microdialysate was pooled every 8 h and analyzed for MMP-1, -2, -7, -9, and -10 using a multiplex immunoassay. Concentrations of MMP-1, -2, and -10 were similar at both monitoring sites and did not show discernible temporal trends. Overall, there was a gradual increase in MMP-7 concentrations in both normal and injured brain over the monitoring period...