@article{RN161,
   author = {Cho, H. J. and Verbridge, S. S. and Davalos, R. V. and Lee, Y. W.},
   title = {Development of an In Vitro 3D Brain Tissue Model Mimicking In Vivo-Like Pro-inflammatory and Pro-oxidative Responses},
   journal = {Ann Biomed Eng},
   volume = {46},
   number = {6},
   pages = {877-887},
   note = {1573-9686
Cho, Hyung Joon
Verbridge, Scott S
Davalos, Rafael V
Lee, Yong W
Journal Article
United States
2018/03/04
Ann Biomed Eng. 2018 Jun;46(6):877-887. doi: 10.1007/s10439-018-2004-z. Epub 2018 Mar 2.},
   abstract = {To analyze complex inflammatory responses in an in vitro system, we constructed a new 3D in vitro brain tissue model that exhibits in vivo-like tissue responses (e.g. immune cell phenotypes, and molecular response) to inflammatory stimuli. Finite element modeling of oxygen diffusion and cellular oxygen consumption predicted the oxygen profile within 3D structures, consisting of Type I collagen hydrogel embedded with murine microglia. Viability and cytotoxicity analyses supported the mathematical analysis, determining optimal cell growth conditions for 3D construct development. Real-time RT-PCR and ELISA demonstrated significant up-regulation of pro-inflammatory mediators, such as TNF-α, MCP-1, IL-6 and IL-1β, in lipopolysaccharide (LPS)-stimulated in vitro cell culture (2D and 3D) and in vivo mouse model systems. Interestingly, levels of inflammatory responses from the in vitro 3D model system were more similar to in vivo than in vitro 2D. Additionally, in situ dihydroethidium (DHE) assay and immunofluorescence staining revealed that levels of LPS-stimulated reactive oxygen species (ROS) generation and microglial activation from in vitro 3D model system were closer to in vivo than in vitro 2D. These results demonstrated that an in vitro 3D model provides more physiologically relevant pro-oxidative and pro-inflammatory environments in brain than an in vitro 2D model.},
   keywords = {Animals
Cell Culture Techniques
Cell Line
Collagen Type I/*chemistry
Cytokines/metabolism
Hydrogels/*chemistry
Inflammation/chemically induced/metabolism/pathology
Lipopolysaccharides/toxicity
Mice
Microglia/*metabolism/pathology
*Models, Biological
*Oxidative Stress
Rats
Collagen hydrogel
Cytokines
Lipopolysaccharide
Microglia
Reactive oxygen species},
   ISSN = {0090-6964},
   DOI = {10.1007/s10439-018-2004-z},
   year = {2018},
   type = {Journal Article}
}

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W."],"bibdata":{"bibtype":"article","type":"Journal Article","author":[{"propositions":[],"lastnames":["Cho"],"firstnames":["H.","J."],"suffixes":[]},{"propositions":[],"lastnames":["Verbridge"],"firstnames":["S.","S."],"suffixes":[]},{"propositions":[],"lastnames":["Davalos"],"firstnames":["R.","V."],"suffixes":[]},{"propositions":[],"lastnames":["Lee"],"firstnames":["Y.","W."],"suffixes":[]}],"title":"Development of an In Vitro 3D Brain Tissue Model Mimicking In Vivo-Like Pro-inflammatory and Pro-oxidative Responses","journal":"Ann Biomed Eng","volume":"46","number":"6","pages":"877-887","note":"1573-9686 Cho, Hyung Joon Verbridge, Scott S Davalos, Rafael V Lee, Yong W Journal Article United States 2018/03/04 Ann Biomed Eng. 2018 Jun;46(6):877-887. doi: 10.1007/s10439-018-2004-z. Epub 2018 Mar 2.","abstract":"To analyze complex inflammatory responses in an in vitro system, we constructed a new 3D in vitro brain tissue model that exhibits in vivo-like tissue responses (e.g. immune cell phenotypes, and molecular response) to inflammatory stimuli. Finite element modeling of oxygen diffusion and cellular oxygen consumption predicted the oxygen profile within 3D structures, consisting of Type I collagen hydrogel embedded with murine microglia. Viability and cytotoxicity analyses supported the mathematical analysis, determining optimal cell growth conditions for 3D construct development. Real-time RT-PCR and ELISA demonstrated significant up-regulation of pro-inflammatory mediators, such as TNF-α, MCP-1, IL-6 and IL-1β, in lipopolysaccharide (LPS)-stimulated in vitro cell culture (2D and 3D) and in vivo mouse model systems. Interestingly, levels of inflammatory responses from the in vitro 3D model system were more similar to in vivo than in vitro 2D. Additionally, in situ dihydroethidium (DHE) assay and immunofluorescence staining revealed that levels of LPS-stimulated reactive oxygen species (ROS) generation and microglial activation from in vitro 3D model system were closer to in vivo than in vitro 2D. These results demonstrated that an in vitro 3D model provides more physiologically relevant pro-oxidative and pro-inflammatory environments in brain than an in vitro 2D model.","keywords":"Animals Cell Culture Techniques Cell Line Collagen Type I/*chemistry Cytokines/metabolism Hydrogels/*chemistry Inflammation/chemically induced/metabolism/pathology Lipopolysaccharides/toxicity Mice Microglia/*metabolism/pathology *Models, Biological *Oxidative Stress Rats Collagen hydrogel Cytokines Lipopolysaccharide Microglia Reactive oxygen species","issn":"0090-6964","doi":"10.1007/s10439-018-2004-z","year":"2018","bibtex":"@article{RN161,\n author = {Cho, H. J. and Verbridge, S. S. and Davalos, R. V. and Lee, Y. W.},\n title = {Development of an In Vitro 3D Brain Tissue Model Mimicking In Vivo-Like Pro-inflammatory and Pro-oxidative Responses},\n journal = {Ann Biomed Eng},\n volume = {46},\n number = {6},\n pages = {877-887},\n note = {1573-9686\nCho, Hyung Joon\nVerbridge, Scott S\nDavalos, Rafael V\nLee, Yong W\nJournal Article\nUnited States\n2018/03/04\nAnn Biomed Eng. 2018 Jun;46(6):877-887. doi: 10.1007/s10439-018-2004-z. Epub 2018 Mar 2.},\n abstract = {To analyze complex inflammatory responses in an in vitro system, we constructed a new 3D in vitro brain tissue model that exhibits in vivo-like tissue responses (e.g. immune cell phenotypes, and molecular response) to inflammatory stimuli. Finite element modeling of oxygen diffusion and cellular oxygen consumption predicted the oxygen profile within 3D structures, consisting of Type I collagen hydrogel embedded with murine microglia. Viability and cytotoxicity analyses supported the mathematical analysis, determining optimal cell growth conditions for 3D construct development. Real-time RT-PCR and ELISA demonstrated significant up-regulation of pro-inflammatory mediators, such as TNF-α, MCP-1, IL-6 and IL-1β, in lipopolysaccharide (LPS)-stimulated in vitro cell culture (2D and 3D) and in vivo mouse model systems. Interestingly, levels of inflammatory responses from the in vitro 3D model system were more similar to in vivo than in vitro 2D. Additionally, in situ dihydroethidium (DHE) assay and immunofluorescence staining revealed that levels of LPS-stimulated reactive oxygen species (ROS) generation and microglial activation from in vitro 3D model system were closer to in vivo than in vitro 2D. These results demonstrated that an in vitro 3D model provides more physiologically relevant pro-oxidative and pro-inflammatory environments in brain than an in vitro 2D model.},\n keywords = {Animals\nCell Culture Techniques\nCell Line\nCollagen Type I/*chemistry\nCytokines/metabolism\nHydrogels/*chemistry\nInflammation/chemically induced/metabolism/pathology\nLipopolysaccharides/toxicity\nMice\nMicroglia/*metabolism/pathology\n*Models, Biological\n*Oxidative Stress\nRats\nCollagen hydrogel\nCytokines\nLipopolysaccharide\nMicroglia\nReactive oxygen species},\n ISSN = {0090-6964},\n DOI = {10.1007/s10439-018-2004-z},\n year = {2018},\n type = {Journal Article}\n}\n\n","author_short":["Cho, H. J.","Verbridge, S. S.","Davalos, R. V.","Lee, Y. 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