Abstract
It is well known that the implantation of electrodes for deep brain stimulation or microelectrode probes for the recording of neuronal activity is always accompanied by the response of the brain’s immune system leading to the formation of a glial scar around the implantation sites. The implantation of electrodes causes massive release of adenosine-5′-triphosphate (ATP) and different cytokines into the extracellular space and activates the microglia. The released ATP and the products of its hydrolysis, such as ADP and adenosine, become the main elements mediating chemotactic sensitivity and motility of microglial cells via subsequent activation of P2Y2,12 as well as A3A/A2A adenosine receptors. The size and density of an insulating sheath around the electrode, formed by microglial cells, are important criteria for the optimization of the signal-to-noise ratio during microelectrode recordings or parameters of electrical current delivered to the brain tissue. Here, we study a purinergic signaling pathway underlying the chemotactic motion of microglia towards implanted electrodes as well as the possible impact of an anti-inflammatory coating consisting of the interleukin-1 receptor antagonist. We present a model describing the formation of a stable aggregate around the electrode due to the joint chemo-attractive action of ATP and ADP and the mixed influence of extracellular adenosine. The bioactive coating is modeled as a source of chemo-repellent located near the electrode surface. The obtained analytical and numerical results allowed us to reveal the dependences of size and spatial location of the insulating sheath on the amount of released ATP and estimate the impact of immune suppressive coating on the scarring process.
Highlights
Nowadays, implantation of electrodes for deep brain recording of neuronal signals and electrical deep brain stimulation (DBS) are widely used for the therapy of several neurologic disorders [2,3,4, 1]
We assumed that the electrode is located in the center of the square domain which allows us to model the realistic situation, when it is symmetrically enwrapped by the microglial cells
We presented a simple mathematical model of the acute chemotactic response of the microglia to the electrode implantation, which is accompanied by a massive release of ATP
Summary
Implantation of electrodes for deep brain recording of neuronal signals and electrical deep brain stimulation (DBS) are widely used for the therapy of several neurologic disorders [2,3,4, 1]. Recent studies reported a decrease in the quality of neuronal signals and the number of functional electrodes in chronic MEA recordings caused by the brain’s immune response [8, 9]. Several clinically used DBS devices use voltage-controlled stimulation, which leads to a strong dependence of the injected current on the impedance of the electrode–tissue interface, which separates electrodes from the surrounding brain tissue [14, 16]. Microglia are clustered around the implant in a reactive tissue sheath and persist throughout the whole lifetime
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