-
Fluids and Barriers of the CNS Dec 2021Contemporary biomarker collection techniques in blood and cerebrospinal fluid have to date offered only modest clinical insights into neurologic diseases such as... (Review)
Review
Contemporary biomarker collection techniques in blood and cerebrospinal fluid have to date offered only modest clinical insights into neurologic diseases such as epilepsy and glioma. Conversely, the collection of human electroencephalography (EEG) data has long been the standard of care in these patients, enabling individualized insights for therapy and revealing fundamental principles of human neurophysiology. Increasing interest exists in simultaneously measuring neurochemical biomarkers and electrophysiological data to enhance our understanding of human disease mechanisms. This review compares microdialysis, microperfusion, and implanted EEG probe architectures and performance parameters. Invasive consequences of probe implantation are also investigated along with the functional impact of biofouling. Finally, previously developed microdialysis electrodes and microperfusion electrodes are reviewed in preclinical and clinical settings. Critically, current and precedent microdialysis and microperfusion probes lack the ability to collect neurochemical data that is spatially and temporally coincident with EEG data derived from depth electrodes. This ultimately limits diagnostic and therapeutic progress in epilepsy and glioma research. However, this gap also provides a unique opportunity to create a dual-sensing technology that will provide unprecedented insights into the pathogenic mechanisms of human neurologic disease.
Topics: Biomarkers; Electrocorticography; Humans; Microdialysis; Nervous System Diseases; Neurophysiological Monitoring
PubMed: 34852829
DOI: 10.1186/s12987-021-00292-x -
Pharmacology, Biochemistry, and Behavior Aug 2008Drug addiction is a process beginning with the initial exposure to a drug of abuse, and leading, in some individuals, to chronic habitual use, and high rates of relapse.... (Review)
Review
Drug addiction is a process beginning with the initial exposure to a drug of abuse, and leading, in some individuals, to chronic habitual use, and high rates of relapse. Microdialysis allows researchers to monitor the neurochemical changes that occur in the brain after the initial exposure to a drug, and the neurochemical changes that occur with repeated exposure. These changes in the brain are often referred to as drug-induced neuroplasticity, and the aim of this article is to review studies that have utilized microdialysis to increase our understanding of the neuroplasticity that occurs in the process of addiction. We will review how several neurotransmitter systems, including glutamate, GABA, the monoamines, and others, are altered after chronic drug exposure, and how microdialysis can be used to determine if putative treatments for addiction can reverse the drug-induced neuroplasticity in these systems. We will also briefly discuss our recent research using a known change in GABA neurotransmission that occurs during reinstatement of drug-seeking to screen for possible novel treatments to prevent relapse. Overall, microdialysis in combination with other behavioral and pharmacological techniques has greatly increased our understanding of addiction-related neuroplasticity, and provides a means for discovering new ways to prevent these changes and treat addiction.
Topics: Animals; Dopamine; Glutamic Acid; Microdialysis; Neuronal Plasticity; Serotonin; Substance-Related Disorders; Synaptic Transmission; gamma-Aminobutyric Acid
PubMed: 17928041
DOI: 10.1016/j.pbb.2007.09.001 -
Journal of Neuroscience Methods Nov 2021Microdialysis is a well validated sampling technique that can be used for pharmacokinetic studies of oncological drugs targeting the central nervous system. This...
BACKGROUND
Microdialysis is a well validated sampling technique that can be used for pharmacokinetic studies of oncological drugs targeting the central nervous system. This technique has also been applied to evaluate tumor metabolism and identify pharmacodynamic biomarkers of drug activity. Despite the potential utility of microdialysis for therapeutic discovery, variability in tumor size and location hamper routine use of microdialysis as a preclinical tool. Quantitative validation of microdialysis membrane location relative to radiographically evident tumor regions could facilitate rigorous preclinical studies. However, a widely accessible standardized workflow for preclinical catheter placement and validation is needed.
NEW METHOD
We provide methods for a workflow to yield tailored placement of microdialysis probes within a murine intracranial tumor and illustrate in an IDH1-mutant patient-derived xenograft (PDX) model. This detailed workflow uses a freely available on-line tool built within 3D-slicer freeware to target microdialysis probe placement within the tumor core and validate probe placement fully within the tumor.
RESULTS
We illustrate use of this workflow to validate microdialysis probe location relative to implanted IDH1-mutant PDXs, using the microdialysis probes to quantify levels of extracellular onco-metabolite D-2 hydroxyglutarate.
COMPARISON WITH EXISTING METHODS
Previous methods have used 3D slicer to reliably measure tumor volumes. Prior microdialysis studies have targeted expected tumor locations without validation.
CONCLUSIONS
The new method offers a streamlined and freely available workflow in 3D slicer to optimize and validate microdialysis probe placement within a murine brain tumor.
Topics: Animals; Brain Neoplasms; Central Nervous System; Humans; Mice; Microdialysis
PubMed: 34390758
DOI: 10.1016/j.jneumeth.2021.109321 -
Current Protocols in Neuroscience Apr 2009Microdialysis is an in vivo sampling technique that permits the quantification of various substances (e.g., neurotransmitters, peptides, electrolytes) in blood and...
Microdialysis is an in vivo sampling technique that permits the quantification of various substances (e.g., neurotransmitters, peptides, electrolytes) in blood and tissue. It is also used to infuse substances into the brain and spinal cord. This unit describes methods for the construction and stereotaxic implantation of microdialysis probes into discrete brain regions of the rat and mouse. Procedures for the conduct of conventional and quantitative microdialysis experiments in the awake and anesthetized rodent are also provided.
Topics: Animals; Brain; Brain Chemistry; Equipment Design; Microdialysis; Microelectrodes; Models, Animal; Rodentia
PubMed: 19340813
DOI: 10.1002/0471142301.ns0702s47 -
Pharmaceutical Research Nov 2022Voriconazole is a therapeutically challenging antifungal drug associated with high interindividual pharmacokinetic variability. As a prerequisite to performing clinical...
PURPOSE
Voriconazole is a therapeutically challenging antifungal drug associated with high interindividual pharmacokinetic variability. As a prerequisite to performing clinical trials using the minimally-invasive sampling technique microdialysis, a comprehensive in vitro microdialysis characterization of voriconazole (VRC) and its potentially toxic N-oxide metabolite (NO) was performed.
METHODS
The feasibility of simultaneous microdialysis of VRC and NO was explored in vitro by investigating the relative recovery (RR) of both compounds in the absence and presence of the other. The dependency of RR on compound combination, concentration, microdialysis catheter and study day was evaluated and quantified by linear mixed-effects modeling.
RESULTS
Median RR of VRC and NO during individual microdialysis were high (87.6% and 91.1%). During simultaneous microdialysis of VRC and NO, median RR did not change (87.9% and 91.1%). The linear mixed-effects model confirmed the absence of significant differences between RR of VRC and NO during individual and simultaneous microdialysis as well as between the two compounds (p > 0.05). No concentration dependency of RR was found (p = 0.284). The study day was the main source of variability (46.3%) while the microdialysis catheter only had a minor effect (4.33%). VRC retrodialysis proved feasible as catheter calibration for both compounds.
CONCLUSION
These in vitro microdialysis results encourage the application of microdialysis in clinical trials to assess target-site concentrations of VRC and NO. This can support the generation of a coherent understanding of VRC pharmacokinetics and its sources of variability. Ultimately, a better understanding of human VRC pharmacokinetics might contribute to the development of personalized dosing strategies.
Topics: Humans; Voriconazole; Microdialysis; Antifungal Agents; Calibration; Oxides
PubMed: 36171344
DOI: 10.1007/s11095-022-03292-0 -
Chinese Journal of Cancer Mar 2011Clinical microdialysis allows a discrete volume of the brain to be sampled for neurochemical analysis of neurotransmitters, metabolites, biomarkers, and drugs. The... (Review)
Review
Clinical microdialysis allows a discrete volume of the brain to be sampled for neurochemical analysis of neurotransmitters, metabolites, biomarkers, and drugs. The technique can be safely used in humans intraoperatively, in the intensive care unit, and in ambulatory settings. Microdialysis probes, micropumps, and analytical equipment are commercially available and have been used extensively for neurochemical monitoring in traumatic brain injury, stroke, and subarachnoid hemorrhage. There has been very limited use of microdialysis in neuro-oncology, but this technique has great promise in the study of the basic neurochemistry of brain tumors, alterations in neurochemistry in response to therapy, and the pharmacokinetics of chemotherapeutic agents. Microdialysis probes may also be used to deliver drugs while simultaneously permitting monitoring of neurochemical changes induced by this therapy.
Topics: Animals; Antineoplastic Agents; Biomarkers; Brain Neoplasms; Glioma; Humans; Microdialysis; Monitoring, Physiologic
PubMed: 21352694
DOI: 10.5732/cjc.010.10588 -
Frontiers in Bioscience (Elite Edition) Jan 2016Cerebral microdialysis is a chemical detection method capable of identifying and simultaneously sampling a wide range of substances in the micromilieu of the monitoring... (Review)
Review
Cerebral microdialysis is a chemical detection method capable of identifying and simultaneously sampling a wide range of substances in the micromilieu of the monitoring probe. The interstitial space of biological tissues and fluids is sampled through a thin fenestrated dialysis catheter inserted into the brain. The technique has been reported in patients with Parkinson's disease. However, the procedure is not widely used by neurosurgeons, possibly owing to unclear indications and poor effective benefits, mostly secondary to significant pitfalls. In spite of the feasibility of microdialysis in humans, many factors can affect the quality of the process. Possible pitfalls include improperly designed probe, probe insertion effects, ineffective perfusion rate, issues to optimize stabilization period, and insufficient volume sample. This article reviews those key technical features necessary for performing microdialysis in humans during deep brain stimulation for Parkinson's Disease.
Topics: Deep Brain Stimulation; Humans; Microdialysis; Parkinson Disease
PubMed: 26709663
DOI: 10.2741/E768 -
ACS Chemical Neuroscience Jul 2023Information about the rates of hydrolysis of neuropeptides by extracellular peptidases can lead to a quantitative understanding of how the steady-state and transient...
Information about the rates of hydrolysis of neuropeptides by extracellular peptidases can lead to a quantitative understanding of how the steady-state and transient concentrations of neuropeptides are controlled. We have created a small microfluidic device that electroosmotically infuses peptides into, through, and out of the tissue to a microdialysis probe outside the head. The device is created by two-photon polymerization (Nanoscribe). Inferring quantitative estimates of a rate process from the change in concentration of a substrate that has passed through tissue is challenging for two reasons. One is that diffusion is significant, so there is a distribution of peptide substrate residence times in the tissue. This affects the product yield. The other is that there are multiple paths taken by the substrate as it passes through tissue, so there is a distribution of residence times and thus reaction times. Simulation of the process is essential. The simulations presented here imply that a range of first order rate constants of more than 3 orders of magnitude is measurable and that 5-10 min is required to reach a steady state value of product concentration following initiation of substrate infusion. Experiments using a peptidase-resistant d-amino acid pentapeptide, yaGfl, agree with simulations.
Topics: Microdialysis; Peptides; Perfusion; Computer Simulation; Neuropeptides
PubMed: 37379416
DOI: 10.1021/acschemneuro.3c00057 -
Fluids and Barriers of the CNS Dec 2023Microdialysis is a technique that can be utilized to sample the interstitial fluid of the central nervous system (CNS), including in primary malignant brain tumors known...
BACKGROUND
Microdialysis is a technique that can be utilized to sample the interstitial fluid of the central nervous system (CNS), including in primary malignant brain tumors known as gliomas. Gliomas are mainly accessible at the time of surgery, but have rarely been analyzed via interstitial fluid collected via microdialysis. To that end, we obtained an investigational device exemption for high molecular weight catheters (HMW, 100 kDa) and a variable flow rate pump to perform microdialysis at flow rates amenable to an intra-operative setting. We herein report on the lessons and insights obtained during our intra-operative HMW microdialysis trial, both in regard to methodological and analytical considerations.
METHODS
Intra-operative HMW microdialysis was performed during 15 clinically indicated glioma resections in fourteen patients, across three radiographically diverse regions in each patient. Microdialysates were analyzed via targeted and untargeted metabolomics via ultra-performance liquid chromatography tandem mass spectrometry.
RESULTS
Use of albumin and lactate-containing perfusates impacted subsets of metabolites evaluated via global metabolomics. Additionally, focal delivery of lactate via a lactate-containing perfusate, induced local metabolic changes, suggesting the potential for intra-operative pharmacodynamic studies via reverse microdialysis of candidate drugs. Multiple peri-operatively administered drugs, including levetiracetam, cefazolin, caffeine, mannitol and acetaminophen, could be detected from one microdialysate aliquot representing 10 min worth of intra-operative sampling. Moreover, clinical, radiographic, and methodological considerations for performing intra-operative microdialysis are discussed.
CONCLUSIONS
Intra-operative HMW microdialysis can feasibly be utilized to sample the live human CNS microenvironment, including both metabolites and drugs, within one surgery. Certain variables, such as perfusate type, must be considered during and after analysis. Trial registration NCT04047264.
Topics: Humans; Microdialysis; Glioma; Extracellular Fluid; Lactic Acid; Catheters; Tumor Microenvironment
PubMed: 38115038
DOI: 10.1186/s12987-023-00497-2 -
Biochemical and Biophysical Research... Dec 2022Although microdialysis is a common in vivo sampling technique, a detailed characterization of the performance of a microdialysis probe used for sampling ethanol...
Although microdialysis is a common in vivo sampling technique, a detailed characterization of the performance of a microdialysis probe used for sampling ethanol molecules has not been conducted. In this work, experimental and computational investigations were carried out to quantitatively study ethanol diffusion characteristics for home-made and commercially available probes. Probe efficiency, i.e. recovery rate (defined as the ethanol concentration in the dialysate to that in the external medium surrounding the probe) was used to characterize the performance. The recovery rate was measured at different perfusion flow rates (0.1, 0.2, 0.5, 1, 1.5, 2 μL/min) and external ethanol concentrations (1, 2.5, 5, 10, 20 mM) with controlled environmental conditions. Effect of temperature was also investigated at 19, 37 and 47 °C. The results show that reducing the flow rate from 2 to 0.1 μL/min at least triples the recovery rate for the home-made probes, and it remains nearly unchanged when varying external ethanol concentration. The performance for two commercial microdialysis probes with different membrane materials and configurations were also determined and have similar recovery rates. Through computational modeling, the diffusion coefficient of ethanol in the semipermeable membrane of the home-made probe was determined by fitting the experimental data, and it was found to be 9 × 10 m/s (R > 0.99). In addition, the depletion effect over time at different flow rates along with estimated in vivo ethanol clearance were simulated numerically, showing that the depletion region shrinks significantly when the flow rate is below 1 μL/min. The results provide better understanding of the diffusion characteristics of the microdialysis probe when used for sampling ethanol which can be used for better interpretation of in vivo measurements and for microdialysis probe optimization.
Topics: Microdialysis; Ethanol; Perfusion; Computer Simulation; Diffusion
PubMed: 36399799
DOI: 10.1016/j.bbrc.2022.10.086