Quantification of clinically applicable stimulation parameters for precision near-organ neuromodulation of human splenic nerves.

Autor: Gupta I; Galvani Bioelectronics, Gunnels Wood Road, Stevenage, SG1 2NY, UK. Isha.8.gupta@galvani.bio., Cassará AM; Foundation for Research on Information Technologies in Society (IT'IS), Zeughausstrasse 43, 8004, Zurich, Switzerland., Tarotin I; Galvani Bioelectronics, Gunnels Wood Road, Stevenage, SG1 2NY, UK., Donega M; Galvani Bioelectronics, Gunnels Wood Road, Stevenage, SG1 2NY, UK., Miranda JA; Galvani Bioelectronics, Gunnels Wood Road, Stevenage, SG1 2NY, UK., Sokal DM; Galvani Bioelectronics, Gunnels Wood Road, Stevenage, SG1 2NY, UK., Ouchouche S; Galvani Bioelectronics, Gunnels Wood Road, Stevenage, SG1 2NY, UK., Dopson W; Galvani Bioelectronics, Gunnels Wood Road, Stevenage, SG1 2NY, UK., Matteucci P; Galvani Bioelectronics, Gunnels Wood Road, Stevenage, SG1 2NY, UK., Neufeld E; Foundation for Research on Information Technologies in Society (IT'IS), Zeughausstrasse 43, 8004, Zurich, Switzerland., Schiefer MA; SimNeurix, LLC, Gainesville, FL, USA., Rowles A; Non Clinical Safety, Research and Development, GlaxoSmithKline, Park Road, Ware, SG12 0DP, UK., McGill P; Bioimaging, GlaxoSmithKline, Park Road, Ware, SG12 0DP, UK., Perkins J; The Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, AL9 7TA, UK., Dolezalova N; Department of Surgery, University of Cambridge, and NIHR Cambridge Biomedical Research Centre, Cambridge, CB2 0QQ, UK., Saeb-Parsy K; Department of Surgery, University of Cambridge, and NIHR Cambridge Biomedical Research Centre, Cambridge, CB2 0QQ, UK., Kuster N; Foundation for Research on Information Technologies in Society (IT'IS), Zeughausstrasse 43, 8004, Zurich, Switzerland.; Swiss Federal Institute of Technology (ETH) Zurich, 8092, Zurich, Switzerland., Yazicioglu RF; Galvani Bioelectronics, Gunnels Wood Road, Stevenage, SG1 2NY, UK., Witherington J; Galvani Bioelectronics, Gunnels Wood Road, Stevenage, SG1 2NY, UK., Chew DJ; Galvani Bioelectronics, Gunnels Wood Road, Stevenage, SG1 2NY, UK. Daniel.j.chew@galvani.bio.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2020 Oct 16; Vol. 3 (1), pp. 577. Date of Electronic Publication: 2020 Oct 16.
DOI: 10.1038/s42003-020-01299-0
Abstrakt: Neuromodulation is a new therapeutic pathway to treat inflammatory conditions by modulating the electrical signalling pattern of the autonomic connections to the spleen. However, targeting this sub-division of the nervous system presents specific challenges in translating nerve stimulation parameters. Firstly, autonomic nerves are typically embedded non-uniformly among visceral and connective tissues with complex interfacing requirements. Secondly, these nerves contain axons with populations of varying phenotypes leading to complexities for axon engagement and activation. Thirdly, clinical translational of methodologies attained using preclinical animal models are limited due to heterogeneity of the intra- and inter-species comparative anatomy and physiology. Here we demonstrate how this can be accomplished by the use of in silico modelling of target anatomy, and validation of these estimations through ex vivo human tissue electrophysiology studies. Neuroelectrical models are developed to address the challenges in translation of parameters, which provides strong input criteria for device design and dose selection prior to a first-in-human trial.
Databáze: MEDLINE
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