The DOI matches its Crossref record; 63 of the 63 references it cites were found in a registry or an index.
Losartan prevents acquired epilepsy via TGF‐β signaling suppression
Open accessAbstract
Objective: Acquired epilepsy is frequently associated with structural lesions after trauma, stroke, and infections. Although seizures are often difficult to treat, there is no clinically applicable strategy to prevent the development of epilepsy in patients at risk. We have recently shown that vascular injury is associated with activation of albumin‐mediated transforming growth factor β (TGF‐β) signaling, and followed by local inflammatory response and epileptiform activity ex vivo. Here we investigated albumin‐mediated TGF‐β signaling and tested the efficacy of blocking the TGF‐β pathway in preventing epilepsy. Methods: We addressed the role of TGF‐β signaling in epileptogenesis in 2 different rat models of vascular injury, combining in vitro and in vivo biochemical assays, gene expression, and magnetic resonance and direct optical imaging for blood–brain barrier permeability and vascular reactivity. Long‐term electrocorticographic recordings were acquired in freely behaving animals. Results: We demonstrate that serum‐derived albumin preferentially induces activation of the activin receptor‐like kinase 5 pathway of TGF‐β receptor I in astrocytes. We further show that the angiotensin II type 1 receptor antagonist, losartan, previously identified as a blocker of peripheral TGF‐β signaling, effectively blocks albumin‐induced TGF‐β activation in the brain. Most importantly, losartan prevents the development of delayed recurrent spontaneous seizures, an effect that persists weeks after drug withdrawal. Interpretation: TGF‐β signaling, activated in astrocytes by serum‐derived albumin, is involved in epileptogenesis. We propose losartan, a drug approved by the US Food and Drug Administration, as an efficient antiepileptogenic therapy for epilepsy associated with vascular injury. Ann Neurol 2014;75:864–875
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Furthermore, in vivo pharmacological blockade of TGFβRI/II using SB431542 and losartan19,20 decreases Smad2/3 signaling in the peri-infarct tissue (Supplementary Fig. 5) during the period of GDF activity after stroke.”
From GDF10 is a signal for axonal sprouting and functional recovery after stroke (2015) · cites this paper as [19]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Learning representations by back-propagating errors
Rumelhart, D. E., Hinton, G. E., & Williams, R. J. (1986) · Nature · doi:10.1038/323533a0 · Cited by 31,892
Mechanisms of TGF-β Signaling from Cell Membrane to the Nucleus
Shi, Y., & Massagué, J. (2003) · Cell · doi:10.1016/s0092-8674(03)00432-x · Cited by 5,860
Astrocyte-endothelial interactions at the blood-brain barrier
Abbott, N. J., Rönnbäck, L., & Hansson, E. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1824 · Cited by 5,595
Structure and function of the blood–brain barrier
Abbott, N. J., Patabendige, A. A. K., Dolman, D. E. M., Yusof, S. R., & Begley, D. J. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.07.030 · Cited by 5,185
TGF-β signalling from cell membrane to nucleus through SMAD proteins
Heldin, C., Miyazono, K., & ten Dijke, P. (1997) · Nature · doi:10.1038/37284 · Cited by 3,697
Massagué, J. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3434 · Cited by 3,239
Massagué, J. (2000) · Nature Reviews Molecular Cell Biology · doi:10.1038/35043051 · Cited by 1,925
The role of inflammation in epilepsy
Vezzani, A., French, J., Bartfai, T., & Baram, T. Z. (2011) · Nature Reviews Neurology · doi:10.1038/nrneurol.2010.178 · Cited by 1,876
Comprehensive Algorithm for Quantitative Real-Time Polymerase Chain Reaction
Zhao, S., & Fernald, R. D. (2005) · Journal of Computational Biology · doi:10.1089/cmb.2005.12.1047 · Cited by 1,314
Restart procedures for the conjugate gradient method
Powell, M. J. D. (1977) · Mathematical programming · doi:10.1007/bf01593790 · Cited by 1,252
Cited by
Sorted by citations
Löscher, W., Potschka, H., Sisodiya, S. M., & Vezzani, A. (2020) · Pharmacological Reviews · doi:10.1124/pr.120.019539 · Cited by 967
Neuroinflammatory pathways as treatment targets and biomarkers in epilepsy
Vezzani, A., Balosso, S., & Ravizza, T. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0217-x · Cited by 928
Neuron–glia interactions in the pathophysiology of epilepsy
Patel, D. C., Tewari, B. P., Chaunsali, L., & Sontheimer, H. W. (2019) · Nature reviews. Neuroscience · doi:10.1038/s41583-019-0126-4 · Cited by 478
Tagge, C. A., Fisher, A. M., Minaeva, O. V., Gaudreau, A., Moncaster, J. A., Zhang, X.-L., Wojnarowicz, M. W., Casey, N. F., Lu, H., Kokiko‐Cochran, O. N., et al. (2017) · Brain · doi:10.1093/brain/awx350 · Cited by 402
Self-citationCommonalities in epileptogenic processes from different acute brain insults: Do they translate?
Klein, P., Dingledine, R. J., Aronica, E., Bernard, C., Blümcke, I., Boison, D., Brodie, M. J., Brooks‐Kayal, A. R., Engel, J., Forcelli, P. A., et al. (2017) · Epilepsia · doi:10.1111/epi.13965 · Cited by 300
Metadata
- Authors
- Bar‐Klein, G., Cacheaux, L. P., Kamintsky, L., Prager, O., Weissberg, I., Schoknecht, K., Cheng, P., Kim, S. Y., Wood, L., Heinemann, U., Kaufer, D., & Friedman, A.
- Affiliations
- Ben-Gurion University of the Negev (IL)
- University of California, Berkeley (US)
- Departments of Physiology and Cell Biology Cognitive and Brain Sciences, Zlotowski Center for Neuroscience, Ben‐Gurion University of the Negev Beer‐Sheva Israel
- Charité – Universitätsmedizin Berlin (DE)
- Helen Wills Neuroscience Institute and Department of Integrative Biology University of California, Berkeley Berkeley CA
- Corresponding author
- Friedman, Alon
- ORCID
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2014-05-28
- Volume
- 75
- Issue
- 6
- Pages
- 864-875
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- PMC
- PMC4077937
- OpenAlex
- W1746603715
- Cited by
- 270
- References
- 63
- Citations by year
- 2026: 18 · 2025: 11 · 2024: 28 · 2023: 24 · 2022: 23 · 2021: 26 · 2020: 29 · 2019: 30 · 2018: 15 · 2017: 26 · 2016: 17 · 2015: 13 · 2014: 10
- FWCI
- 16.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (RO1/NINDS NS066005)
- United States - Israel Binational Science Foundation (2007185)
- Israel Science Foundation (713/11)
- The European Unions Seventh Framework Program (FP7/2007-2013), EPITARGET (602102)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Epilepsy research and treatment
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- losartan, acquired epilepsy, epileptogenesis, TGF-beta signaling, serum albumin, vascular injury, angiotensin II type 1 receptor, ALK5, astrocytes, blood-brain barrier permeability, vascular reactivity, antiepileptogenic therapy, spontaneous seizures, electrocorticography
- MeSH terms
- Animals, Animals, Newborn, Anticonvulsants, Astrocytes, Benzamides, Blood-Brain Barrier, Cells, Cultured, Cerebral Cortex, Dioxoles, Disease Models, Animal, Embryo, Mammalian, Endocytosis, Epilepsy, Male, Neurons, Phosphopyruvate Hydratase, Signal Transduction, Transforming Growth Factor beta, Rats, Wistar, Losartan, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
