Mathematical modeling of chemotaxis and glial scarring around implanted electrodes

It is well known that the implantation of electrodes for deep brain stimulation ormicroelectrode 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 causesmassive release of adenosine-5′-triphosphate (ATP) and different cytokines into the extracellular space and activates themicroglia. The releasedATP and the products of its hydrolysis, such asADP and adenosine, become themain elementsmediating chemotactic sensitivity andmotility ofmicroglial 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 bymicroglial cells, are important criteria for the optimization of the signal-to-noise ratio duringmicroelectrode recordings or parameters of electrical current delivered to the brain tissue.Here, we study a purinergic signaling pathway underlying the chemotacticmotion ofmicroglia towards implanted electrodes as well as the possible impact of an anti-inflammatory coating consisting of the interleukin-1 receptor antagonist.We present amodel describing the formation of a stable aggregate around the electrode due to the joint chemo-attractive action of ATP andADP and themixed influence of extracellular adenosine. The bioactive coating ismodeled 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 releasedATP and estimate the impact of immune suppressive coating on the scarring process.