Revealing Spatial and Temporal Patterns of Cell Death, Glial Proliferation, and Blood-Brain Barrier Dysfunction Around Implanted Intracortical Neural Interfaces

Improving the long-term performance of neural electrode interfaces requires overcoming severe biological reactions such as neuronal cell death, glial cell activation, and vascular damage in the presence of implanted intracortical devices. Past studies traditionally observe neurons, microglia, astroc...

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Main Authors: Steven M. Wellman, Lehong Li, Yalikun Yaxiaer, Ingrid McNamara, Takashi D. Y. Kozai
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-05-01
Series:Frontiers in Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fnins.2019.00493/full
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spelling doaj-5a67e30375fe454faba01adbb286b46d2020-11-25T01:34:00ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2019-05-011310.3389/fnins.2019.00493448562Revealing Spatial and Temporal Patterns of Cell Death, Glial Proliferation, and Blood-Brain Barrier Dysfunction Around Implanted Intracortical Neural InterfacesSteven M. Wellman0Steven M. Wellman1Lehong Li2Yalikun Yaxiaer3Ingrid McNamara4Takashi D. Y. Kozai5Takashi D. Y. Kozai6Takashi D. Y. Kozai7Takashi D. Y. Kozai8Takashi D. Y. Kozai9Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United StatesCenter for the Neural Basis of Cognition, Pittsburgh, PA, United StatesDepartment of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United StatesEberly College of Science, Pennsylvania State University, University Park, PA, United StatesDepartment of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United StatesCenter for the Neural Basis of Cognition, Pittsburgh, PA, United StatesCenter for Neuroscience, University of Pittsburgh, Pittsburgh, PA, United StatesMcGowan Institute of Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesNeuroTech Center, University of Pittsburgh Brain Institute, Pittsburgh, PA, United StatesImproving the long-term performance of neural electrode interfaces requires overcoming severe biological reactions such as neuronal cell death, glial cell activation, and vascular damage in the presence of implanted intracortical devices. Past studies traditionally observe neurons, microglia, astrocytes, and blood-brain barrier (BBB) disruption around inserted microelectrode arrays. However, analysis of these factors alone yields poor correlation between tissue inflammation and device performance. Additionally, these studies often overlook significant biological responses that can occur during acute implantation injury. The current study employs additional histological markers that provide novel information about neglected tissue components—oligodendrocytes and their myelin structures, oligodendrocyte precursor cells, and BBB -associated pericytes—during the foreign body response to inserted devices at 1, 3, 7, and 28 days post-insertion. Our results reveal unique temporal and spatial patterns of neuronal and oligodendrocyte cell loss, axonal and myelin reorganization, glial cell reactivity, and pericyte deficiency both acutely and chronically around implanted devices. Furthermore, probing for immunohistochemical markers that highlight mechanisms of cell death or patterns of proliferation and differentiation have provided new insight into inflammatory tissue dynamics around implanted intracortical electrode arrays.https://www.frontiersin.org/article/10.3389/fnins.2019.00493/fulloligodendrocytesNG2 gliapericytestissue-electrode interfaceneurodegenerationgliosis
collection DOAJ
language English
format Article
sources DOAJ
author Steven M. Wellman
Steven M. Wellman
Lehong Li
Yalikun Yaxiaer
Ingrid McNamara
Takashi D. Y. Kozai
Takashi D. Y. Kozai
Takashi D. Y. Kozai
Takashi D. Y. Kozai
Takashi D. Y. Kozai
spellingShingle Steven M. Wellman
Steven M. Wellman
Lehong Li
Yalikun Yaxiaer
Ingrid McNamara
Takashi D. Y. Kozai
Takashi D. Y. Kozai
Takashi D. Y. Kozai
Takashi D. Y. Kozai
Takashi D. Y. Kozai
Revealing Spatial and Temporal Patterns of Cell Death, Glial Proliferation, and Blood-Brain Barrier Dysfunction Around Implanted Intracortical Neural Interfaces
Frontiers in Neuroscience
oligodendrocytes
NG2 glia
pericytes
tissue-electrode interface
neurodegeneration
gliosis
author_facet Steven M. Wellman
Steven M. Wellman
Lehong Li
Yalikun Yaxiaer
Ingrid McNamara
Takashi D. Y. Kozai
Takashi D. Y. Kozai
Takashi D. Y. Kozai
Takashi D. Y. Kozai
Takashi D. Y. Kozai
author_sort Steven M. Wellman
title Revealing Spatial and Temporal Patterns of Cell Death, Glial Proliferation, and Blood-Brain Barrier Dysfunction Around Implanted Intracortical Neural Interfaces
title_short Revealing Spatial and Temporal Patterns of Cell Death, Glial Proliferation, and Blood-Brain Barrier Dysfunction Around Implanted Intracortical Neural Interfaces
title_full Revealing Spatial and Temporal Patterns of Cell Death, Glial Proliferation, and Blood-Brain Barrier Dysfunction Around Implanted Intracortical Neural Interfaces
title_fullStr Revealing Spatial and Temporal Patterns of Cell Death, Glial Proliferation, and Blood-Brain Barrier Dysfunction Around Implanted Intracortical Neural Interfaces
title_full_unstemmed Revealing Spatial and Temporal Patterns of Cell Death, Glial Proliferation, and Blood-Brain Barrier Dysfunction Around Implanted Intracortical Neural Interfaces
title_sort revealing spatial and temporal patterns of cell death, glial proliferation, and blood-brain barrier dysfunction around implanted intracortical neural interfaces
publisher Frontiers Media S.A.
series Frontiers in Neuroscience
issn 1662-453X
publishDate 2019-05-01
description Improving the long-term performance of neural electrode interfaces requires overcoming severe biological reactions such as neuronal cell death, glial cell activation, and vascular damage in the presence of implanted intracortical devices. Past studies traditionally observe neurons, microglia, astrocytes, and blood-brain barrier (BBB) disruption around inserted microelectrode arrays. However, analysis of these factors alone yields poor correlation between tissue inflammation and device performance. Additionally, these studies often overlook significant biological responses that can occur during acute implantation injury. The current study employs additional histological markers that provide novel information about neglected tissue components—oligodendrocytes and their myelin structures, oligodendrocyte precursor cells, and BBB -associated pericytes—during the foreign body response to inserted devices at 1, 3, 7, and 28 days post-insertion. Our results reveal unique temporal and spatial patterns of neuronal and oligodendrocyte cell loss, axonal and myelin reorganization, glial cell reactivity, and pericyte deficiency both acutely and chronically around implanted devices. Furthermore, probing for immunohistochemical markers that highlight mechanisms of cell death or patterns of proliferation and differentiation have provided new insight into inflammatory tissue dynamics around implanted intracortical electrode arrays.
topic oligodendrocytes
NG2 glia
pericytes
tissue-electrode interface
neurodegeneration
gliosis
url https://www.frontiersin.org/article/10.3389/fnins.2019.00493/full
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