Dexamethasone-Enhanced Microdialysis and Penetration Injury

Microdialysis probes, electrochemical microsensors, and neural prosthetics are often used for in vivo 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. Modulation of the immune response is an important step toward making these devices with reliable long-term performance. Local release of anti-inflammatory agents such as dexamethasone (DEX) are often used to mitigate the foreign body response. In this article microdialysis is used to locally deliver DEX to the surrounding brain tissue. This work discusses the immune response resulting from microdialysis probe implantation. We briefly review the principles of microdialysis and the applications of DEX with microdialysis in (i) neuronal devices, (ii) dopamine and fast scan cyclic voltammetry, (iii) the attenuation of microglial cells, (iv) macrophage polarization states, and (v) spreading depolarizations. The difficulties and complexities in these applications are herein discussed.

Contribution of serotonin receptor subtypes to hallucinogenic activity of 25I-NBOMe and to its effect on neurotransmission

Background 4-Iodo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (25I-NBOMe) is a potent serotonin (5-HT) receptor agonist with hallucinogenic properties. The aim of our research was to examine the role of the 5-HT2A, 5-HT2C and 5-HT1A serotonin receptor subtypes in 25I-NBOMe hallucinogenic activity and its effect on dopamine (DA), 5-HT and glutamate release in the rat frontal cortex. Methods Hallucinogenic activity was investigated using the wet dog shake (WDS) test. The release of DA, 5-HT and glutamate in the rat frontal cortex was studied using a microdialysis in freely moving rats. Neurotransmitter levels were analyzed by HPLC with electrochemical detection. The selective antagonists of the 5-HT2A, 5-HT2C and 5-HT1A serotonin receptor subtypes: M100907, SB242084 and WAY100635, respectively were applied through a microdialysis probe. Results The WDS response to 25I-NBOMe (1 and 3 mg/kg) was significantly reduced by local administration of M100907 and SB242084 (100 nM). The 25I-NBOMe-induced increase in glutamate, DA and 5-HT release was inhibited by M100907 and SB242084. WAY100635 had no effect on 25I-NBOMe-induced WDS and glutamate release, while it decreased DA and 5-HT release from cortical neuronal terminals. Conclusion The obtained results suggest that 5-HT2A and 5-HT2C receptors play a role in 25I-NBOMe-induced hallucinogenic activity and in glutamate, DA and 5-HT release in the rat frontal cortex as their respective antagonists attenuated the effect of this hallucinogen. The disinhibition of GABA cells by the 5-HT1A receptor antagonist seems to underlie the mechanism of decreased DA and 5-HT release from neuronal terminals in the frontal cortex.

Dexamethasone Sodium Phosphate Penetration During Phonophoresis at 2 Ultrasound Frequencies

Context The effect of ultrasound frequency on phonophoresis drug delivery in humans is unknown. Objective To determine if a low (45-kHz) or high (1-MHz) frequency delivered a higher dexamethasone (Dex) concentration through the skin. Design Controlled laboratory study. Setting Laboratory. Patients or Other Participants A total of 40 healthy men between the ages of 18 and 45 years (age = 23.1 ± 2.6 years, height = 176.1 ± 7.2 cm, mass = 88.5 ± 19.4 kg, posterior calf subcutaneous thickness measured using musculoskeletal ultrasound imaging = 0.6 ± 0.2 cm). Intervention(s) Participants were randomly assigned to 1 of 4 groups (ultrasound frequency at microdialysis probe depth): (1) 45-kHz frequency at 1 mm, (2) 45-kHz frequency at 4 mm, (3) 1-MHz frequency at 1 mm, or (4) 1-MHz frequency at 4 mm (n = 10 in each group). Three linear microdialysis probes were inserted at the desired tissue depth. We rubbed dexamethasone sodium phosphate (Dex-P) into the skin and then applied a 15-minute phonophoresis treatment. Main Outcome Measure(s) Dialysate was collected during the treatment and 60 minutes posttreatment and analyzed for Dex-P, Dex, and the metabolite form of Dex. The sum of the 3 analytes was calculated as total dexamethasone (Dex-total), and differences between the 45-kHz and 1-MHz treatment groups were determined by a repeated-measures analysis of variance. Results At 1 mm, 3 (30%) participants in the 45-kHz and 4 (40%) participants in the 1-MHz group had measurable levels of Dex-P. Total dexamethasone increased after the treatment ceased, independent of ultrasound frequency (P < .001), with a trend of the 45-kHz treatment to produce a greater increase in drug concentration (P = .006). At 4 mm, 5 (50%) participants in the 45-kHz and 1 (10%) participant in the 1-MHz group had measurable levels of Dex-P. We observed no difference in Dex-total concentration between treatment groups at 4 mm (P = .72). Conclusions Phonophoresis provided a mechanism for Dex-total delivery at the 1- and 4-mm tissue depths. However, the effectiveness of the ultrasound frequencies varied between the 2 measured tissue depths.

Real-time analysis of ATP concentration in acupoints during acupuncture: a new technique combining microdialysis with patch clamp

This paper introduces a new technique combining microdialysis with patch clamp to detect the changes in ATP (adenosine triphosphate) concentration in acupoints during acupuncture. The microdialysis probe was implanted into the Zusanli acupoint (ST 36) of adult SD (Sprague Dawley) rats to sample acupoint fluid containing ATP released during acupuncture. Then, the fluid with ATP was delivered in real time to 293 T cells overexpressing P2X3 receptors, with which we could carry out patch clamp experiments. The results showed that changes in membrane currents could reflect changes in the concentration of ATP. Thus, we can successfully detect ATP released in acupoints during acupuncture in real time. This technique provides us with a new way to study the mechanism of acupuncture signal initiation.

The Effect of Microdialysis Catheter Insertion on Glutamate and Serotonin Levels in Masseter Muscle in Patients with Myofascial Temporomandibular Disorders and Healthy Controls

Myofascial temporomandibular disorders (TMD) are the most common cause of chronic pain in the orofacial region. Microdialysis has been used to study metabolic changes in the human masseter muscle. The insertion of the microdialysis probe causes acute tissue trauma that could affect the metabolic milieu and thereby influence the results when comparing healthy subjects to those with TMD. This study aimed to investigate the levels of serotonin and glutamate during the acute tissue trauma period in healthy subjects and in patients with TMD. Microdialysis was carried out in 15 patients with TMD and 15 controls, and samples were collected every 20 min during a period of 140 min. No significant alterations of serotonin or glutamate were observed over the 2 h period for the healthy subjects. For the TMD group, a significant decrease in serotonin was observed over time (p < 0.001), followed by a significant increase between 120 and 140 min (p < 0.001). For glutamate, a significant reduction was observed at 40 min compared to baseline. The results showed that there was a spontaneous increase of serotonin 2 h after the insertion of the catheter in patients with TMD. In conclusion, the results showed that there are differences in the masseter muscle levels of serotonin and glutamate during acute nociception in patients with myofascial TMD compared to healthy subjects.

Development of a MD-LC-MS/MS Method to Analyze 3 Bioactive Compounds in Huoxuezhitong Rubber Patch and Application to a Pharmacokinetic Study in Rats

Huoxuezhitong rubber patch, a well-known traditional Chinese medicine (TCM) prescription, is utilized to treat pain and inflammation. In this study, a microdialysis-ultra-high-performance liquid chromatography-tandem mass spectrometry (MD-LC-MS/MS) method was designed for the simultaneous determination of active constituents in the rubber patch, such as paeonol (Pae), eugenol (Eug), and piperine (Pip). A microdialysis probe was implanted in the subcutaneous tissue of a rat, which is intended to detect the subcutaneous concentrations of target components. Saline containing 30% ethanol acted as perfusion fluid. Analytes in the microdialysate were completely separated over an ACQITY UPLC RBEH C18column (2.1mm×100mm, 1.7μm). The mobile phase was composed of 0.01% ammonia aqueous and acetonitrile-0.01% ammonia with gradient elution. The single-run analysis time was 10.0 minutes. The linear regression displayed good linear relationships in the ranges of 0.25–100 ng/mL for paeonol and eugenol and 0.001–5 ng/mL for piperine. The interday and intraday precision of the quality control samples exhibited relative standard deviations (RSD) <13.56%. The accuracy values ranged from −14.92% to 14.00%. The present method was successfully applied in pharmacokinetics studies following dermal administration of Huoxuezhitong rubber patch in rats. Pip’sTmax(488.00±150.73) min was greater than that of Pae (186.67±48.44) min and Eug (240.00±138.56) min, and the rank order of t1/2was Pae > Pip > Eug. The rank order of AUC0-720andCmaxwas both Eug > Pae > Pip. MRT0-∞of Pip was higher than that of Pae and Eug. Eugenol showed a faster elimination and a shorter half-life. Paeonol showed a stronger drug reservoir function after removing the drug source.