Dexamethasone-Enhanced Continuous Online Microdialysis for Neuromonitoring of O after Brain Injury.

Traumatic brain injury (TBI) is a major public health crisis in many regions of the world. Severe TBI may cause a primary brain lesion with a surrounding penumbra of tissue that is vulnerable to secondary injury. Secondary injury presents as progressive expansion of the lesion, possibly leading to severe disability, a persistent vegetive state, or death.

Validation of Dexamethasone-Enhanced Continuous-Online Microdialysis for Monitoring Glucose for 10 Days after Brain Injury.

Traumatic brain injury (TBI) induces a pathophysiologic state that can be worsened by secondary injury. Monitoring brain metabolism with intracranial microdialysis can provide clinical insights to limit secondary injury in the days following TBI. Recent enhancements to microdialysis include the implementation of continuously operating electrochemical biosensors for monitoring the dialysate sample stream in real time and dexamethasone retrodialysis to mitigate the tissue response to probe insertion.

Miniaturized probe on polymer SU-8 with array of individually addressable microelectrodes for electrochemical analysis in neural and other biological tissues.

An SU-8 probe with an array of nine, individually addressable gold microband electrodes (100 μm long, 4 μm wide, separated by 4-μm gaps) was photolithographically fabricated and characterized for detection of low concentrations of chemicals in confined spaces and in vivo studies of biological tissues. The probe's shank (6 mm long, 100 μm wide, 100 μm thick) is flexible, but exhibits sufficient sharpness and rigidity to be inserted into soft tissue. Laser micromachining was used to define probe geometry by spatially revealing the underlying sacrificial aluminum layer, which was then etched to free the probes from a silicon wafer.

In vivo evidence for the unique kinetics of evoked dopamine release in the patch and matrix compartments of the striatum.

The neurochemical transmitter dopamine (DA) is implicated in a number of diseases states, including Parkinson's disease, schizophrenia, and drug abuse. DA terminal fields in the dorsal striatum and core region of the nucleus accumbens in the rat brain are organized as heterogeneous domains exhibiting fast and slow kinetic of DA release. The rates of dopamine release are significantly and substantially faster in the fast domains relative to the slow domains.

Dexamethasone-Enhanced Microdialysis and Penetration Injury.

Microdialysis probes, electrochemical microsensors, and neural prosthetics are often used for monitoring, but these are invasive devices that are implanted directly into brain tissue. Although the selectivity, sensitivity, and temporal resolution of these devices have been characterized in detail, less attention has been paid to the impact of the trauma they inflict on the tissue or the effect of any such trauma on the outcome of the measurements they are used to perform. Factors affecting brain tissue reaction to the implanted devices include: the mechanical trauma during insertion, the foreign body response, implantation method, and physical properties of the device (size, shape, and surface characteristics.

Electroosmotic Perfusion-Microdialysis Probe Created by Direct Laser Writing for Quantitative Assessment of Leucine Enkephalin Hydrolysis by Insulin-Regulated Aminopeptidase in Vivo.

There are many processes that actively alter the concentrations of solutes in the extracellular space. Enzymatic reactions, either by soluble enzymes or membrane-bound ectoenzymes, and uptake or clearance are two such processes. Investigations of ectoenzymatic reactions in vivo is challenging, particularly in the brain.

Electrokinetic Convection-Enhanced Delivery of Solutes to the Brain.

Pressure-induced infusion of solutions into brain tissue is used both in research and in medicine. In medicine, convection enhanced delivery (CED) may be used to deliver agents to localized areas of the brain, such as with gene therapy to functional targets or with deep tumors not readily amenable to resection. However, clinical trials have demonstrated mixed results from CED.

A rotating operant chamber for use with microdialysis.

Background: Recently, the time resolution of microdialysis followed by a chemical separation for quantitative analysis has improved. The advent of faster microdialysis measurements promises to aid in behavioral research on awake animals. However, microdialysis with awake animals generally employs a fluidic commutator (swivel).

Extended (10-Day) Real-Time Monitoring by Dexamethasone-Enhanced Microdialysis in the Injured Rat Cortex.

Intracerebral microdialysis has proven useful for chemical monitoring in patients following traumatic brain injury. Recent studies in animals, however, have documented that insertion of microdialysis probes into brain tissues initiates a foreign-body response. Within a few days after probe insertion, the foreign body response impedes the use of microdialysis to monitor the K and glucose transients associated with spreading depolarization, a potential mechanism for secondary brain injury.

Electrokinetic infusions into hydrogels and brain tissue: Control of direction and magnitude of solute delivery.

Background: Delivering solutes to a particular region of the brain is currently achieved by iontophoresis for very small volumes and by diffusion from a microdialysis probe for larger volumes. There is a need to deliver solutes to particular areas with more control than is possible with existing methods.

New Method: Electrokinetic infusions of solutes were performed into hydrogels and organotypic hippocampal slice cultures.

On-Column Dimethylation with Capillary Liquid Chromatography-Tandem Mass Spectrometry for Online Determination of Neuropeptides in Rat Brain Microdialysate.

We have developed a method for online collection and quantitation of neuropeptides in rat brain microdialysates using on-column dimethylation with capillary liquid chromatography-tandem mass spectrometry (cLC-MS). This method addresses a number of the challenges of quantifying neuropeptides with cLC-MS. It is also a completely automated and robust method for the preparation of stable isotope labeled-peptide internal standards to correct for matrix effects and thus ensure accurate quantitation.

Enhancing Continuous Online Microdialysis Using Dexamethasone: Measurement of Dynamic Neurometabolic Changes during Spreading Depolarization.

Microdialysis is well established in chemical neuroscience as a mainstay technology for real time intracranial chemical monitoring in both animal models and human patients. Evidence shows that microdialysis can be enhanced by mitigating the penetration injury caused during the insertion of microdialysis probes into brain tissue. Herein, we show that retrodialysis of dexamethasone in the rat cortex enhances the microdialysis detection of K and glucose transients induced by spreading depolarization.

Enhanced Intracranial Microdialysis by Reduction of Traumatic Penetration Injury at the Probe Track.

Microdialysis provides deep insight into chemical neuroscience by enabling in vivo intracranial chemical monitoring. Nevertheless, implanting a microdialysis probe causes a traumatic penetration injury (TPI) of brain tissue at the probe track. The TPI, which is clearly documented by voltammetry and histochemical imaging, is a drawback because it perturbs the exact tissue from which the brain dialysate samples are derived.

Dexamethasone retrodialysis attenuates microglial response to implanted probes in vivo.

Intracortical neural probes enable researchers to measure electrical and chemical signals in the brain. However, penetration injury from probe insertion into living brain tissue leads to an inflammatory tissue response. In turn, microglia are activated, which leads to encapsulation of the probe and release of pro-inflammatory cytokines.

A review of the effects of FSCV and microdialysis measurements on dopamine release in the surrounding tissue.

Microdialysis is commonly used in neuroscience to obtain information about the concentration of substances, including neurotransmitters such as dopamine (DA), in the extracellular space (ECS) of the brain. Measuring DA concentrations in the ECS with in vivo microdialysis and/or voltammetry is a mainstay of investigations into both normal and pathological function of central DA systems. Although both techniques are instrumental in understanding brain chemistry each has its shortcomings.

Kinetic diversity of dopamine transmission in the dorsal striatum.

Dopamine (DA), a highly significant neurotransmitter in the mammalian central nervous system, operates on multiple time scales to affect a diverse array of physiological functions. The significance of DA in human health is heightened by its role in a variety of pathologies. Voltammetric measurements of electrically evoked DA release have brought to light the existence of a patchwork of DA kinetic domains in the dorsal striatum (DS) of the rat.

Brain tissue responses to neural implants impact signal sensitivity and intervention strategies.

Implantable biosensors are valuable scientific tools for basic neuroscience research and clinical applications. Neurotechnologies provide direct readouts of neurological signal and neurochemical processes. These tools are generally most valuable when performance capacities extend over months and years to facilitate the study of memory, plasticity, and behavior or to monitor patients' conditions.

Microdialysis in the rat striatum: effects of 24 h dexamethasone retrodialysis on evoked dopamine release and penetration injury.

The power of microdialysis for in vivo neurochemical monitoring is a result of intense efforts to enhance microdialysis procedures, the probes themselves, and the analytical systems used for the analysis of dialysate samples. Our goal is to refine microdialysis further by focusing attention on what happens when the probes are implanted into brain tissue. It is broadly acknowledged that some tissue damage occurs, such that the tissue nearest the probes is disrupted from its normal state.

In vivo monitoring of serotonin in the striatum of freely moving rats with one minute temporal resolution by online microdialysis-capillary high-performance liquid chromatography at elevated temperature and pressure.

Online monitoring of serotonin in striatal dialysate from freely moving rats was carried out for more than 16 h at 1 min time resolution using microdialysis coupled online to a capillary HPLC system operating at about 500 bar and 50 °C. Several aspects of the system were optimized toward robust, in vivo online measurements. A two-loop, eight-port rotary injection valve demonstrated better consistency of continuous injections than the more commonly used two-loop, 10-port valve.

Pharmacological mitigation of tissue damage during brain microdialysis.

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.

Optimization for speed and sensitivity in capillary high performance liquid chromatography. The importance of column diameter in online monitoring of serotonin by microdialysis.

The speed of a separation defines the best time resolution possible in online measurements using chromatography. The desired time resolution multiplied by the flow rate of the stream of analyte being sampled defines the maximum volume of sample per injection. The best concentration sensitivity in chromatography is obtained by injecting the largest volume of sample that is consistent with achieving a satisfactory separation, and thus measurement accuracy.

A method for the intracranial delivery of reagents to voltammetric recording sites.

Carbon fiber microelectrodes are widely used for electrochemical monitoring in the intact brain. The local delivery of reagents to the recording site is often desirable. The approach of co-implanting a micropipette near the microelectrode presents some limitations that are overcome by the use of double-barreled devices.

Domain-dependent effects of DAT inhibition in the rat dorsal striatum.

The rat dorsal striatum exhibits domain-dependent kinetics of dopamine release and clearance. The present report describes the domain-dependent actions of nomifensine (20 mg/kg i.p.

Effect of dexamethasone on gliosis, ischemia, and dopamine extraction during microdialysis sampling in brain tissue.

Microdialysis sampling of the brain is an analytical technique with numerous applications in neuroscience and the neurointensive care of brain-injured human patients. Even so, implanting microdialysis probes into brain tissue causes a penetration injury that triggers gliosis (the activation and proliferation of glial cells) and ischemia (the interruption of blood flow). Thus, the probe samples injured tissue.