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Analysis of institutional authors

Cuadrado Pastor, AntonioAuthorInnamorato NAuthorRojo AAuthorGarcía-Yagüe AAuthor

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October 19, 2020
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The transcription factor nrf2 is a therapeutic target against brain inflammation

Publicated to:JOURNAL OF IMMUNOLOGY. 181 (1): 680-689 - 2008-07-01 181(1), DOI: 10.4049/jimmunol.181.1.680

Authors: Innamorato, Nadia G; Rojo, Ana I; Garcia-Yaguee, Angel J; Yamamoto, Masayuki; de Ceballos, Maria L; Cuadrado, Antonio

Affiliations

Centro de Investigacion Biomedica en Red de Enfermedades Neurodegenerativas - Author
CSIC - Instituto Cajal (IC) - Author
CSIC, Inst Cajal, Dept Neurobiol Celular Mol & Desarrollo, E-28002 Madrid, Spain - Author
Ctr Invest Red Enfermedades Neurodegenerat, Madrid, Spain - Author
Univ Autonoma Madrid, Fac Med, Dept Bioquim, E-28029 Madrid, Spain - Author
Univ Autonoma Madrid, Fac Med, Inst Invest Biomed, Alberto Sols Consejo Super Invest Cient, E-28029 Madrid, Spain - Author
Univ Tsukuba, Ctr Tsukuba Adv Alliance, Tsukuba, Ibaraki, Japan - Author
Univ Tsukuba, Inst Basic Med Sci, Tsukuba, Ibaraki 305, Japan - Author
Universidad Autónoma de Madrid - Author
Universidad Autonoma de Madrid, Facultad de Medicina - Author
University of Tsukuba - Author
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Abstract

Because chronic neuroinflammation is a hallmark of neurodegenerative diseases and compromises neuron viability, it is imperative to discover pharmacologic targets to modulate the activation of immune brain cells, the microglia. In this study, we identify the transcription factor Nrf2, guardian of redox homeostasis, as such target in a model of LPS-induced inflammation in mouse hippocampus. Nrf2 knockout mice were hypersensitive to the neuroinflammation induced by LPS, as determined by an increase in F4/80 mRNA and protein, indicative of an increase in microglial cells, and in the inflammation markers inducible NO synthase, IL-6, and TNF-α, compared with the hippocampi of wild-type littermates. The aliphatic isothiocyanate sulforaphane elicited an Nrf2-mediated antioxidant response in the BV2 microglial cell line, determined by flow cytometry of cells incubated with the redox sensitive probe dihydrodichlorofluorescein diacetate, and by the Nrf2-dependent induction of the phase II antioxidant enzyme heme oxygenase-1. Animals treated with sulforaphane displayed a 2-3-fold increase in heme oxygenase-1, a reduced abundance of microglial cells in the hippocampus and an attenuated production of inflammation markers (inducible NO synthase, IL-6, and TNF-α) in response to LPS. Considering that release of reactive oxygen species is a property of activated microglia, we propose a model in which late induction of Nrf2 intervenes in the down-regulation of microglia. This study opens the possibility of targeting Nrf2 in brain as a means to modulate neuroinflammation. Copyright © 2008 by The American Association of Immunologists, Inc.

Keywords

AnimalsAntioxidant response elementAstrocytesBilirubinCarbon-monoxideCell lineEncephalitisExpressionGene expression regulation, enzymologicGenesHeme oxygenase-1HippocampusIsothiocyanatesKappa-bLipopolysaccharidesMaleMiceMice, inbred c57blMice, knockoutMicrogliaNf-e2-related factor 2SulforaphaneSulfoxidesThiocyanates

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal JOURNAL OF IMMUNOLOGY due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2008, it was in position 16/121, thus managing to position itself as a Q1 (Primer Cuartil), in the category Immunology.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 29.85, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-18, the following number of citations:

  • WoS: 407
  • Scopus: 430
  • Europe PMC: 291

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-18:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 210.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 212 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 6.5.
  • The number of mentions on the social network Facebook: 4 (Altmetric).
  • The number of mentions on the social network X (formerly Twitter): 5 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Japan.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (INNAMORATO ., NADIA GISELLE) and Last Author (Cuadrado A).

the author responsible for correspondence tasks has been Cuadrado A.