Microdialysis in the Rat Striatum: Effects of 24 h Dexamethasone Retrodialysis on Evoked Dopamine Release and Penetration Injury

Abstract

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. We hypothesize that mitigating such disruption would refine microdialysis. Herein, we show that the addition of dexamethasone, an anti-inflammatory drug, to the perfusion fluid protects evoked dopamine responses as measured by fast-scan cyclic voltammetry next to the probes after 24 h. We also show that dexamethasone stabilizes evoked dopamine responses measured at the probe outlet over a 4–24 h postimplantation interval. The effects of dexamethasone are attributable to its anti-inflammatory actions, as dexamethasone had no significant effect on two histochemical markers for dopamine terminals, tyrosine hydroxylase and the dopamine transporter. Using histochemical assays, we confirmed that the actions of dexamethasone are tightly confined to the immediate, local vicinity of the probe.

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

“…Recent work on the microdialysis of dopamine in the rat striatum shows that DEX reduces ischemia, suppresses glial activation, protects neurons and neuronal terminals, and reinstates normal dopamine activity in the tissues surrounding microdialysis probes. [32][33][34][35][36] Here, we report that DEX also offers substantial benefits to the microdialysis of SDassociated glucose and K + transients in the rat cortex. We inserted microdialysis probes into the cortex of rats and monitored glucose and K + 2 hrs, 5 days, or 10 days later.…”

“…The insertion SD supports prior conclusions that probe insertion causes a penetration injury. [28][29][30][31][32][33][34][35][36][37][38][39][40][41] Two additional examples of complete recordings of K + and glucose from single animals are provided in the Supplementary Information document. Figure S1 is an example with needle pricks that produced neither a K + spike nor a glucose dip.…”

“…Previous studies from the rat striatum have established that probe insertion triggers ischemia in the vicinity of the probe and that a glial barrier eventually surrounds and engulfs the probe, thereby hindering long-term sampling. [28][29][30][31][32][33][34][35][36] Adding DEX to the perfusion fluid reduces ischemia and suppresses gliosis. Consistent with these prior reports, the present study confirms that DEX retrodialysis enhances the performance of microdialysis monitoring also in the rat cortex.…”

“…[26][27] Nevertheless, inserting the probe into brain tissue causes a penetration injury. [28][29][30][31][32][33][34][35] In response, the host tissue engulfs the probe in a glial barrier that, once formed, impairs further microdialysis sampling. 32,[36][37][38][39][40][41] This is a limitation for clinical microdialysis, as TBI patients often remain under intensive care for 10 days or more.…”

Microdialysis Monitoring in Clinical Traumatic Brain Injury and Its Role in Neuroprotective Drug Development

“…Delivery of 13 C-labelled substrates focally into brain via the microdialysis catheter and simultaneous recovery of the 13 Clabelled metabolites in the emerging microdialysate has been successfully performed in TBI patients (28,96,97). In preclinical experiments, retrodialysis has recently been shown to successfully deliver dexamethasone directly in both experimental TBI with ameliorating effects (98) and to transgenic animals expressing decreased microglia activity (99).…”