Abstract

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.

Highlights

  • Because microdialysis is highly compatible with awake-behaving animals, numerous studies have examined the relationships between chemical events in the extracellular space of the brain and animal behaviors (Becker and Cha, 1989; Robinson and Justice, 1991; Castner et al, 1993; Borjigin and Liu, 2008)

  • This study demonstrated that DEX stabilizes, but does not alter, evoked DA responses at the outlet of microdialysis probes

  • We found that implantation of the microdialysis probe with DEX reduced microglial activation

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Summary

INTRODUCTION

Microdialysis is a powerful technique for near real-time intracranial chemical monitoring in both animal models and human patients (Roberts and Anderson, 1979; Ungerstedt, 1984, 1991; Benveniste et al, 1987, 1989; Benveniste, 1989; Santiago and Westerink, 1990; Carneheim and Stahle, 1991; Parsons et al, 1991; Dykstra et al, 1992; Stenken, 1999; Hutchinson et al, 2000; Chefer et al, 2001; Stenken et al, 2001, 2010; Bosche et al, 2003, 2010; Schuck et al, 2004; Ungerstedt and Rostami, 2004; Parkin et al, 2005; Shou et al, 2006; Mitala et al, 2008; Hashemi et al, 2009; Jaquins-Gerstl et al, 2011; Wang and Michael, 2012; Zhang et al, 2013; Nesbitt et al, 2015; Dreier et al, 2016). Our failure to detect evoked dopamine release at the probe outlet was not a matter of temporal resolution but rather was a matter of tissue disruption: there was no evoked response taking place in the surrounding tissue (Borland et al, 2005) This finding raised our initial concerns that the tissue surrounding the probe was in an abnormal, most likely traumatized, state and prompted our subsequent focus on the issue of penetration trauma and, eventually, strategies to mitigate it. Dexamethasone-enhanced microdialysis offers key and specific benefits It has facilitated the detection of evoked dopamine release at the probe outlet, resolving the technical difficulty described above. This is a matter that potential adopters of DEX-enhanced microdialysis will need to evaluate in the future in the context of their own particular intended applications

PRINCIPLES OF MICRODIALYSIS
Penetration Trauma
Strategies to Reduce Inflammation
DEX and Neuronal Devices
Dopamine Microdialysis and Detection With Fast Scan Cyclic Voltammetry
Attenuate the inflammatory response and reduce neuronal loss
Stabilizes evoked dopamine responses and protects DA terminals
DEX Retrodialysis Attenuates Microglial Activity
Findings
Spreading Depolarizations and Microdialysis
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