Universität zu Köln

Silchenko, Alexander N. and Tass, Peter A. (2015). Mathematical modeling of chemotaxis and glial scarring around implanted electrodes. New J. Phys., 17. BRISTOL: IOP PUBLISHING LTD. ISSN 1367-2630

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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 P2Y(2,12) 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Silchenko, Alexander N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tass, Peter A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-414240
DOI:	10.1088/1367-2630/17/2/023009
Journal or Publication Title:	New J. Phys.
Volume:	17
Date:	2015
Publisher:	IOP PUBLISHING LTD
Place of Publication:	BRISTOL
ISSN:	1367-2630
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INDUCED ATP RELEASE; EXTRACELLULAR ATP; BRAIN-TISSUE; MICROGLIA; RECEPTOR; AGGREGATION; NEURONS; INHIBITION; ACTIVATION; RESPONSES Multiple languages Physics, Multidisciplinary Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/41424