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

Abstract

Microdialysis is well established in chemical neuroscience as a mainstay technology for real time intracranial chemical monitoring in both animal models and human patients. The capabilities of microdialysis sampling have the potential to be further enhanced through mitigation of the penetration injury unavoidably caused by the insertion of microdialysis probes into brain tissue. Herein, we show that dexamethasone retrodialysis in the rat cortex enhances the microdialysis detection of K+ and glucose transients induced by spreading depolarization. Once inserted, the probes were perfused continuously (1.67 μL/min) either with or without dexamethasone. Without dexamethasone, glucose transients were too small to reliably quantify at 5 days after probe insertion. With dexamethasone, robust K+ and glucose transients were readily quantified at 2 hrs, 5 days, and 10 days after probe insertion. Although the amplitudes of the K+ transients declined day-to-day following probe insertion, amplitudes of the glucose transients were consistent. Immunohistochemistry and fluorescence microscopy confirm that dexamethasone is highly effective at preventing ischemia and gliosis in the vicinity of microdialysis probes implanted for 10 days.

Measurement of Basal Neurotransmitter Levels Using Convolution-Based Nonfaradaic Current Removal

“…The convolution-based approach used here is described in ref (21). Briefly, a waveform with a small amplitude pulse placed immediately prior to the FSCV sweep is used.…”

3D printed microfluidic device for online detection of neurochemical changes with high temporal resolution in human brain microdialysate

“…34 SDs have been associated with the development of secondary damage and have been shown to independently predict poor patient outcome. [35][36][37] The electrophysiological and chemical signatures of SDs have been recorded both in animal models 22,[38][39][40][41] and clinically. 24,42,43 The occurrence of an SD wave is reflected in the local tissue by a transient increase in the extracellular levels of potassium and glutamate, coupled with a simultaneous decrease in glucose and increase in lactate, indicating a high energy demand.…”

Dexamethasone-Enhanced Microdialysis and Penetration Injury

“…Our group reported that DEX conferred profound benefits to the microdialysis monitoring of SDs induced glucose and K + transients in the rat cortex, Figure 7 (Varner et al, 2017). We inserted microdialysis probes, with and without retrodialysis of DEX, and monitored SD-induced glucose and K + transients 2 h, 5 days, or 10 days later (Varner et al, 2017). SDs were induced by needle pricks and were performed at 30-min intervals.…”