Microdialysis of dopamine interpreted with quantitative model incorporating probe implantation trauma

Abstract

Although microdialysis is widely used to sample endogenous and exogenous substances in vivo, interpretation of the results obtained by this technique remains controversial. The goal of the present study was to examine recent criticism of microdialysis in the specific case of dopamine (DA) measurements in the brain extracellular microenvironment. The apparent steady-state basal extracellular concentration and extraction fraction of DA were determined in anesthetized rat striatum by the concentration difference (no-net-flux) microdialysis technique. A rate constant for extracellular clearance of DA calculated from the extraction fraction was smaller than the previously determined estimate by fast-scan cyclic voltammetry for cellular uptake of DA. Because the relatively small size of the voltammetric microsensor produces little tissue damage, the discrepancy between the uptake rate constants may be a consequence of trauma from microdialysis probe implantation. The trauma layer has previously been identified by histology and proposed to distort measurements of extracellular DA levels by the no-net-flux method. To address this issue, an existing quantitative mathematical model for microdialysis was modified to incorporate a traumatized tissue layer interposed between the probe and surrounding normal tissue. The tissue layers are hypothesized to differ in their rates of neurotransmitter release and uptake. A post-implantation traumatized layer with reduced uptake and no release can reconcile the discrepancy between DA uptake measured by microdialysis and voltammetry. The model predicts that this trauma layer would cause the DA extraction fraction obtained from microdialysis in vivo calibration techniques, such as no-net-flux, to differ from the DA relative recovery and lead to an underestimation of the DA extracellular concentration in the surrounding normal tissue.

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

“…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.…”

“…[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. Emerging evidence suggests that retrodialysis of dexamethasone (DEX), a glucocorticoid anti-inflammatory steroid, may be a simple yet effective strategy for mitigating the probe penetration injury.…”

Are Cutaneous Microdialysis Cytokine Findings Supported by End Point Biopsy Immunohistochemistry Findings?

“…As we and others have found, passage of cytokines through the PES membrane is not only dependent upon the molecular weight but is also far more complex and includes the actual structure, charge and other molecule characteristics of the proteins (17,18,25,35). Much of this work is of common interest for all researchers using microdialysis.…”

“…For larger molecules like cytokines, blood flow is probably less important, although the question is as yet not fully elucidated. After the short-term changes (17), deposition of proteinaceous material on the catheter membrane referred to as "biofouling" (19,22,40) can be suspected of causing changes in catheter membrane performance. Such deposition is reported to occur within the 24-h time frame of this experiment (40), but our findings indicate that they do not necessarily preclude an attempt at interpretation of findings.…”

“…The issues of tissue reactivity, levels of trauma and recovery (equilibration) times are central to any discussion of CMD. This is especially so in the interpretation of findings on cytokines and other biologically active molecules such as chemokines and growth factors (9,10,(17)(18)(19), which patently have longer "equilibration" times than axon reflex-mediated microvascular events (11)(12)(13). Other central issues concern whether membranes retain their laboratory bench determined function in relation to passage of target molecules in vivo in the short-(e.g.…”