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Modeling the Inflam...
Modeling the Inflammatory Response of Traumatic Brain Injury Using Human Induced Pluripotent Stem Cell Derived Microglia
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- Alam, Aftab (author)
- Univ Cambridge, Dept Clin Neurosci, Cambridge, England.
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- Singh, Tanya (author)
- Cardiff Univ, Sch Biosci, Cardiff, Wales.;Cardiff Univ, Neurosci & Mental Hlth Innovat Inst, Cardiff, Wales.
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- Kayhanian, Saeed (author)
- Univ Cambridge, Dept Clin Neurosci, Cambridge, England.;Univ Cambridge, Cambridge Biomed Campus, Cambridge CB2 0QQ, England.
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- Tjerkaski, Jonathan (author)
- Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
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- Garcia, Nuria Marco (author)
- Univ Cambridge, Dept Clin Neurosci, Cambridge, England.
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- Carpenter, Keri L. H. (author)
- Karolinska Institutet,Univ Cambridge, Dept Clin Neurosci, Cambridge, England.
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- Patani, Rickie (author)
- UCL, Inst Neurol, Queen Sq, London, England.
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- Lindblad, Caroline (author)
- Uppsala universitet,Förvärvade hjärnskador,Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
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- Thelin, Eric P. P. (author)
- Karolinska Institutet,Univ Cambridge, Dept Clin Neurosci, Cambridge, England.;Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Neurol, Stockholm, Sweden.
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- Syed, Yasir Ahmed (author)
- Cardiff Univ, Sch Biosci, Cardiff, Wales.;Cardiff Univ, Neurosci & Mental Hlth Innovat Inst, Cardiff, Wales.
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- Helmy, Adel (author)
- Univ Cambridge, Dept Clin Neurosci, Cambridge, England.
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Univ Cambridge, Dept Clin Neurosci, Cambridge, England Cardiff Univ, Sch Biosci, Cardiff, Wales.;Cardiff Univ, Neurosci & Mental Hlth Innovat Inst, Cardiff, Wales. (creator_code:org_t)
- Mary Ann Liebert, 2023
- 2023
- English.
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In: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 40:19-20, s. 2164-2173
- Related links:
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https://doi.org/10.1...
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Abstract
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- The neuroinflammatory response after traumatic brain injury (TBI) is implicated as a key mediator of secondary injury in both the acute and chronic periods after primary injury. Microglia are the key innate immune cell in the central nervous system, responding to injury with the release of cytokines and chemokines. In this context, we aimed to characterize the downstream cytokine response of human induced pluripotent stem cell (iPSC)-derived microglia when stimulated with five separate cytokines identified after human TBI. The iPSC-derived microglia were exposed to interleukin (IL)-1 & beta;, IL-4, IL-6, IL-10, and tumor necrosis factor (TNF) in the concentration ranges identified in clinical TBI studies. The downstream cytokine response was measured against a panel of 37 separate cytokines over a 72h time-course. The secretome revealed concentration-, time- and combined concentration and time-dependent downstream responses. TNF appeared to be the strongest inducer of downstream cytokine changes (51), followed by IL-1 & beta; (26) and IL-4 (19). IL-10 (11) and IL-6 (10) produced fewer responses. We also compare these responses with our previous studies of iPSC-derived neuronal and astrocyte cultures and the in vivo human TBI cytokine response. Notably, we found microglial culture to induce both a wider range of downstream cytokine responses and a greater fold change in concentration for those downstream responses, compared with astrocyte and neuronal cultures. In summary, we present a dataset for human microglial cytokine responses specific to the secretome found in the clinical context of TBI. This reductionist approach complements our previous datasets for astrocyte and neuronal responses and will provide a platform to enable future studies to unravel the complex neuroinflammatory network activated after TBI.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- cytokine
- inflammation
- microdialysis
- microglia
- neuroinflammation
- traumatic brain injury
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Alam, Aftab
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Singh, Tanya
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Kayhanian, Saeed
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Tjerkaski, Jonat ...
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Garcia, Nuria Ma ...
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Carpenter, Keri ...
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show more...
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Patani, Rickie
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Lindblad, Caroli ...
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Thelin, Eric P. ...
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Syed, Yasir Ahme ...
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Helmy, Adel
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Neurology
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Journal of Neuro ...
- By the university
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Uppsala University
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Karolinska Institutet