Microfluidic Model to Evaluate Astrocyte Activation in Penumbral Region following Ischemic Stroke

Stroke is one of the main causes of death in the US and post-stroke treatment options remain limited. Ischemic stroke is caused by a blood clot that compromises blood supply to the brain, rapidly leading to tissue death at the core of the infarcted area surrounded by a hypoxic and nutrient-starved r...

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Main Authors: Kathryn M. Denecke, Catherine A. McBain, Brock G. Hermes, Sireesh Kumar Teertam, Mehtab Farooqui, María Virumbrales-Muñoz, Jennifer Panackal, David J. Beebe, Bolanle Famakin, Jose M. Ayuso
Format: Article
Language:English
Published: MDPI AG 2022-07-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/11/15/2356
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author Kathryn M. Denecke
Catherine A. McBain
Brock G. Hermes
Sireesh Kumar Teertam
Mehtab Farooqui
María Virumbrales-Muñoz
Jennifer Panackal
David J. Beebe
Bolanle Famakin
Jose M. Ayuso
author_facet Kathryn M. Denecke
Catherine A. McBain
Brock G. Hermes
Sireesh Kumar Teertam
Mehtab Farooqui
María Virumbrales-Muñoz
Jennifer Panackal
David J. Beebe
Bolanle Famakin
Jose M. Ayuso
author_sort Kathryn M. Denecke
collection DOAJ
description Stroke is one of the main causes of death in the US and post-stroke treatment options remain limited. Ischemic stroke is caused by a blood clot that compromises blood supply to the brain, rapidly leading to tissue death at the core of the infarcted area surrounded by a hypoxic and nutrient-starved region known as the penumbra. Recent evidence suggests that astrocytes in the penumbral region play a dual role in stroke response, promoting further neural and tissue damage or improving tissue repair depending on the microenvironment. Thus, astrocyte response in the hypoxic penumbra could promote tissue repair after stroke, salvaging neurons in the affected area and contributing to cognitive recovery. However, the complex microenvironment of ischemic stroke, characterized by gradients of hypoxia and nutrients, poses a unique challenge for traditional in vitro models, which in turn hinders the development of novel therapies. To address this challenge, we have developed a novel, polystyrene-based microfluidic device to model the necrotic and penumbral region induced by an ischemic stroke. We demonstrated that when subjected to hypoxia, and nutrient starvation, astrocytes within the penumbral region generated in the microdevice exhibited long-lasting, significantly altered signaling capacity including calcium signaling impairment.
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spelling doaj.art-57d268607c0c4150aec10d241ecd85b52023-11-30T22:16:03ZengMDPI AGCells2073-44092022-07-011115235610.3390/cells11152356Microfluidic Model to Evaluate Astrocyte Activation in Penumbral Region following Ischemic StrokeKathryn M. Denecke0Catherine A. McBain1Brock G. Hermes2Sireesh Kumar Teertam3Mehtab Farooqui4María Virumbrales-Muñoz5Jennifer Panackal6David J. Beebe7Bolanle Famakin8Jose M. Ayuso9Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53705, USADepartment of Dermatology, University of Wisconsin-Madison, Madison, WI 53705, USADepartment of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53705, USADepartment of Neurology, University of Wisconsin-Madison, Madison, WI 53705, USADepartment of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53705, USADepartment of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53705, USADepartment of Neurology, University of Wisconsin-Madison, Madison, WI 53705, USADepartment of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53705, USADepartment of Neurology, University of Wisconsin-Madison, Madison, WI 53705, USADepartment of Dermatology, University of Wisconsin-Madison, Madison, WI 53705, USAStroke is one of the main causes of death in the US and post-stroke treatment options remain limited. Ischemic stroke is caused by a blood clot that compromises blood supply to the brain, rapidly leading to tissue death at the core of the infarcted area surrounded by a hypoxic and nutrient-starved region known as the penumbra. Recent evidence suggests that astrocytes in the penumbral region play a dual role in stroke response, promoting further neural and tissue damage or improving tissue repair depending on the microenvironment. Thus, astrocyte response in the hypoxic penumbra could promote tissue repair after stroke, salvaging neurons in the affected area and contributing to cognitive recovery. However, the complex microenvironment of ischemic stroke, characterized by gradients of hypoxia and nutrients, poses a unique challenge for traditional in vitro models, which in turn hinders the development of novel therapies. To address this challenge, we have developed a novel, polystyrene-based microfluidic device to model the necrotic and penumbral region induced by an ischemic stroke. We demonstrated that when subjected to hypoxia, and nutrient starvation, astrocytes within the penumbral region generated in the microdevice exhibited long-lasting, significantly altered signaling capacity including calcium signaling impairment.https://www.mdpi.com/2073-4409/11/15/2356strokeastroyctesmicroenviromentmicrofluidics
spellingShingle Kathryn M. Denecke
Catherine A. McBain
Brock G. Hermes
Sireesh Kumar Teertam
Mehtab Farooqui
María Virumbrales-Muñoz
Jennifer Panackal
David J. Beebe
Bolanle Famakin
Jose M. Ayuso
Microfluidic Model to Evaluate Astrocyte Activation in Penumbral Region following Ischemic Stroke
Cells
stroke
astroyctes
microenviroment
microfluidics
title Microfluidic Model to Evaluate Astrocyte Activation in Penumbral Region following Ischemic Stroke
title_full Microfluidic Model to Evaluate Astrocyte Activation in Penumbral Region following Ischemic Stroke
title_fullStr Microfluidic Model to Evaluate Astrocyte Activation in Penumbral Region following Ischemic Stroke
title_full_unstemmed Microfluidic Model to Evaluate Astrocyte Activation in Penumbral Region following Ischemic Stroke
title_short Microfluidic Model to Evaluate Astrocyte Activation in Penumbral Region following Ischemic Stroke
title_sort microfluidic model to evaluate astrocyte activation in penumbral region following ischemic stroke
topic stroke
astroyctes
microenviroment
microfluidics
url https://www.mdpi.com/2073-4409/11/15/2356
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