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

Abstract

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. Herein, we show that perfusing microdialysis probes with dexamethasone, a potent anti-inflammatory glucocorticoid, suppresses the foreign body response and facilitates the monitoring of spontaneous spreading depolarizations for at least 10 days following controlled cortical injury in the rat. In addition to spreading depolarizations, results of this study suggest that a progressive, apparently permanent, decline in pericontusional interstitial glucose may be an additional sequela of brain injury. This study establishes extended dexamethasone-enhanced microdialysis in the injured rodent cortex as a new paradigm for investigating trauma-induced metabolic crisis.

Dexamethasone-Enhanced Microdialysis and Penetration Injury

“…We also observed a second post-CCI phenomenon consisting of a slow, progressive decline of dialysate glucose from basal concentrations to levels below the detection limit ( Robbins et al, 2019 ). Once this occurred, glucose concentrations did not return to detectable levels.…”

“…Our most recent study was to investigate whether the microdialysis with DEX is translatable to the monitoring of spontaneous SD in rats after controlled cortical impact (CCI), a widely studied rodent model of TBI ( Dixon et al, 1987 ; Wagner et al, 2005 ; Xiong et al, 2013 ). Microdialysis probes were placed 1 or 3 mm away from the CCI site expecting that the secondary injury would spread over time into the penumbra ( Robbins et al, 2019 ). But this did not happen.…”

“…There was no difference between 1 and 3 mm location of the probes. We recorded K + and glucose in dialysates from 10 rats for 10–12 days following CCI and microdialysis probe insertion ( Robbins et al, 2019 ). Overall, recordings from n = 8 rats exhibited 185 spontaneous SDs, hallmarked by a transient rise, and fall in dialysate K + , over the course of 5–7 min.…”

Recent Advances in In Vivo Neurochemical Monitoring

“…Recent advances in anti-inflammatory drug delivery through the perfusate [ 228 , 229 , 230 ] and ultrasmall microfabricated nano-probe development [ 219 ] have improved the tissue/probe interface, resulting in longer-lasting in vivo measurements. By perfusing the anti-inflammatory corticosteroid dexamethasone through the microdialysis probe, glucose levels in TBI model rats have been continuously monitored for upwards of 10 days without glial barrier formation [ 231 ].…”

Real-Time Fast Scan Cyclic Voltammetry Detection and Quantification of Exogenously Administered Melatonin in Mice Brain

“…Concentric style microdialysis probes were fabricated as previously described (Nesbitt et al, 2015;Varner et al, 2016;Robbins et al, 2019). Briefly, the probes were constructed in-house using hollow fiber membranes (18 kDa molecular weight cutoff, Spectra/Por RC, Spectrum, Rancho Dominguez, CA, United States) with a 280 µm OD, cut to a length of 1.5 mm.…”