Tumor Necrosis Factor-α Mediates the Blood–Brain Barrier Dysfunction Induced by Activated Microglia in Mouse Brain Microvascular Endothelial Cells
Open accessAbstract
The present study was designed to elucidate the involvement of tumor necrosis factor-alpha (TNF-alpha) release from activated microglia in the induction of blood-brain barrier (BBB) dysfunction in an in vitro co-culture system with mouse brain capillary endothelial cells (MBEC4) and microglia. Lipopolysaccharide (LPS)-activated microglia increased the permeability of MBEC4 cells to sodium-fluorescein, and this hyper-permeability was blocked by a neutralizing antibody against TNF-alpha. LPS stimulated microglia to facilitate TNF-alpha release. These findings suggested that TNF-alpha released from activated microglia is attributable to BBB dysfunction.
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TNF-α released from activated microglia contributes to BBB dysfunction.
“indicating that TNF-α contributes to BBB dysfunction (Nishioku et al., 2010).”
From The impact of microglial activation on blood-brain barrier in brain diseases (2014) · cites this paper as Nishioku et al., 2010
LPS induces production of TNF-α in the brain by microglial cells, which promotes BBB dysfunction and also causes neuronal cell death by phagocytosis.
“On the other hand, it has been shown that LPS induces the production of TNF-α in the brain by microglial cells, which promotes BBB dysfunction and also causes neuronal cell death by phagocytosis (Tanaka et al., 2006; Nishioku et al., 2010; Smith et al., 2012; Neniskyte et al., 2014).”
From The impact of microglial activation on blood-brain barrier in brain diseases (2014) · cites this paper as Nishioku et al., 2010
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The Blood-Brain Barrier in Health and Chronic Neurodegenerative Disorders
Zlokovic, B. V. (2008) · Neuron · doi:10.1016/j.neuron.2008.01.003 · Cited by 3,280 · see citing works
Ryu, J. K., & McLarnon, J. G. (2009) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2008.00434.x · Cited by 406 · see citing works
Yenari, M. A., Xu, L., Tang, X. N., Qiao, Y., & Giffard, R. G. (2006) · Stroke · doi:10.1161/01.str.0000206281.77178.ac · Cited by 359 · see citing works
Functional involvement of P-glycoprotein in blood-brain barrier.
Tatsuta, T., Naito, M., Oh‐hara, T., Sugawara, I., & TSURUO, T. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)88713-6 · Cited by 348 · see citing works
Adams, R. A., Bauer, J., Flick, M. J., Sikorski, S. L., Nuriel, T., Lassmann, H., Degen, J. L., & Akassoglou, K. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20061931 · Cited by 335 · see citing works
Ozaki, H., Ishii, K., Horiuchi, H., Arai, H., Kawamoto, T., Okawa, K., Iwamatsu, A., & Kita, T. (1999) · PubMed · Cited by 270 · see citing works
Ozaki, H., Ishii, K., Horiuchi, H., Arai, H., Kawamoto, T., Okawa, K., Iwamatsu, A., & Kita, T. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.2.553 · Cited by 235 · see citing works
Nishioku, T., Dohgu, S., Takata, F., Eto, T., Ishikawa, N., Kodama, K., Nakagawa, S., Yamauchi, A., & Kataoka, Y. (2008) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-008-9322-x · Cited by 210 · see citing works
Self-citationTNF-α knockout and minocycline treatment attenuates blood–brain barrier leakage in MPTP-treated mice
Zhao, C., Ling, Z., Newman, M. B., Bhatia, A., & Carvey, P. M. (2007) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.11.012 · Cited by 183 · see citing works
Sumi, N., Nishioku, T., Takata, F., Matsumoto, J., Watanabe, T., Shuto, H., Yamauchi, A., Dohgu, S., & Kataoka, Y. (2010) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-009-9446-7 · Cited by 179 · see citing works
Self-citationMark, K. S., & Miller, D. W. (1999) · Life Sciences · doi:10.1016/s0024-3205(99)00139-3 · Cited by 143 · see citing works
Silwedel, C., & Förster, C. Y. (2006) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2006.06.019 · Cited by 105 · see citing works
Osburg, B., Peiser, C., Dömling, D., Schomburg, L., Ko, Y., Voigt, K., & Bickel, U. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00436.2001 · Cited by 100 · see citing works
Dohgu, S., Yamauchi, A., Takata, F., Naito, M., Tsuruo, T., Higuchi, S., Sawada, Y., & Kataoka, Y. (2004) · Cellular and Molecular Neurobiology · doi:10.1023/b:cemn.0000022776.47302.ce · Cited by 96 · see citing works
Self-citationNADPH oxidase mediates vascular endothelial cadherin phosphorylation and endothelial dysfunction
Nwariaku, F. E., Liu, Z., Zhu, X., Nahari, D., Ingle, C., Wu, R. F., Gu, Y., Sarosi, G., & Terada, L. S. (2004) · Blood · doi:10.1182/blood-2004-05-1868 · Cited by 78 · see citing works
Brändle, D., Bilsborough, J., Rülicke, T., Uyttenhove, C., Boon, T., & den Eynde, B. J. V. (1998) · European Journal of Immunology · doi:10.1002/(sici)1521-4141(199812)28:12 · Cited by 62 · see citing works
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Research works printed but not linked: 1
- Lou J, Gasche Y, Zheng L, Critico B, Monso-Hinard C, Juillard P, et al. Differential reactivity of brain microvascular endothelial cells to TNF reflects the genetic susceptibility to cerebral malaria. Eur J Immunol. 1998;28:3989-4000.
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da Fonseca, A. C. C., Matias, D., Garcia, C., Amaral, R., Geraldo, L. H., Freitas, C., & Lima, F. R. S. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00362 · Cited by 572 · see citing works
How do immune cells overcome the blood-brain barrier in multiple sclerosis?
Larochelle, C., Alvarez, J. I., & Prat, A. (2011) · FEBS Letters · doi:10.1016/j.febslet.2011.04.066 · Cited by 405 · see citing works
Rochfort, K. D., Collins, L. E., Murphy, R. P., & Cummins, P. M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0101815 · Cited by 261 · see citing works
Development and Function of the Blood-Brain Barrier in the Context of Metabolic Control
Haddad-Tóvolli, R., Dragano, N. R. V., Ramalho, A. F. S., & Velloso, L. A. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00224 · Cited by 226 · see citing works
Zielinski, M. R., Dunbrasky, D. L., Taishi, P., Souza, G., & Krueger, J. M. (2013) · Sleep · doi:10.5665/sleep.2892 · Cited by 94 · see citing works
Microglia recapitulate a hematopoietic master regulator network in the aging human frontal cortex
Wehrspaun, C. C., Haerty, W., & Ponting, C. P. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.04.008 · Cited by 64 · see citing works
Microglia activation contributes to quinolinic acid-induced neuronal excitotoxicity through TNF-α
Feng, W., Wang, Y., Liu, Z.-Q., Zhang, X., Han, R., Miao, Y.-Z., & Qin, Z.-H. (2017) · Apoptosis · doi:10.1007/s10495-017-1363-5 · Cited by 53 · see citing works
- Authors
- Nishioku, T., Matsumoto, J., Dohgu, S., Sumi, N., Miyao, K., Takata, F., Shuto, H., Yamauchi, A., & Kataoka, Y.
- Affiliations
- Fukuoka University (JP)
- Venue
- Journal of Pharmacological Sciences
- Publisher
- Japanese Pharmacological Society
- Published
- 2010
- Volume
- 112
- Issue
- 2
- Pages
- 251-254
- ISSN
- 1347-8613 (ISSN-L)
- 1347-8648
- OpenAlex
- W2047074480
- Cited by
- 168
- References
- 16
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 13 · 2023: 14 · 2022: 14 · 2021: 15 · 2020: 17 · 2019: 7 · 2018: 12 · 2017: 11 · 2016: 8 · 2015: 10 · 2014: 12 · 2013: 4 · 2012: 7
- FWCI
- 3.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Pharmacological Sciences (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- University of Tokyo
- Japan Society for the Promotion of Science (21790526, 21790257, 21790102, 20800066, 21790255, 17390159)
- Division of Molecular and Cellular Biosciences
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- TNF-α, blood-brain barrier dysfunction, microglial activation, brain microvascular endothelial cells, endothelial permeability, lipopolysaccharide, anti-TNF-alpha antibody, neuroinflammation
- MeSH terms
- Animals, Blood-Brain Barrier, Brain, Capillaries, Cell Membrane Permeability, Endothelium, Vascular, Lipopolysaccharides, Mice, Inbred BALB C, Tumor Necrosis Factor-alpha, Microglia, Coculture Techniques, Fluorescein, Mice
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