The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Tissue-type plasminogen activator induces opening of the blood-brain barrier via the LDL receptor–related protein
Open accessAbstract
The regulation of cerebrovascular permeability is critical for normal brain homeostasis, and the "breakdown" of the blood-brain barrier (BBB) is associated with the development of vasogenic edema and intracranial hypertension in a number of neurological disorders. In this study we demonstrate that an increase in endogenous tissue-type plasminogen activator (tPA) activity in the perivascular tissue following cerebral ischemia induces opening of the BBB via a mechanism that is independent of both plasminogen (Plg) and MMP-9. We also show that injection of tPA into the cerebrospinal fluid in the absence of ischemia results in a rapid dose-dependent increase in vascular permeability. This activity is not seen with urokinase-type Plg activator (uPA) but is induced in Plg-/- mice, confirming that the effect is Plg-independent. However, the activity is blocked by antibodies to the LDL receptor-related protein (LRP) and by the LRP antagonist, receptor-associated protein (RAP), suggesting a receptor-mediated process. Together these studies demonstrate that tPA is both necessary and sufficient to directly increase vascular permeability in the early stages of BBB opening, and suggest that this occurs through a receptor-mediated cell signaling event and not through generalized degradation of the vascular basement membrane.
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.
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
The Mouse Brain in Stereotaxic Coordinates
Paxinos, G. (2001) · Cited by 12,862
Tissue Plasminogen Activator for Acute Ischemic Stroke
(1995) · New England Journal of Medicine · doi:10.1056/nejm199512143332401 · Cited by 11,654
Benardete, E. A., & Nair, A. K. (2015) · Cerebrovascular Diseases Extra · doi:10.1159/000370060 · Cited by 2,546
The anticonvulsant MK-801 is a potent N-methyl-D-aspartate antagonist.
Wong, E. H., Kemp, J. A., Priestley, T., Knight, A. R., Woodruff, G. N., & Iversen, L. L. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.18.7104 · Cited by 1,819
Vu, T. H., Shipley, J. M., Bergers, G., Berger, J. E., Helms, J. A., Hanahan, D., Shapiro, S. D., Senior, R. M., & Werb, Z. (1998) · Cell · doi:10.1016/s0092-8674(00)81169-1 · Cited by 1,750
Tight junctions of the blood–brain barrier
Wolburg, H., & Lippoldt, A. (2002) · Vascular Pharmacology · doi:10.1016/s1537-1891(02)00200-8 · Cited by 1,183
Asahi, M., Wang, X., Mori, T., Sumii, T., Jung, J.-C., Moskowitz, M. A., Fini, M. E., & Lo, E. H. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-19-07724.2001 · Cited by 1,004
THE CELL BIOLOGY OF THE BLOOD-BRAIN BARRIER
Rubin, L. L., & Staddon, J. M. (1999) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.22.1.11 · Cited by 1,000
Herz, J., Hamann, U., Rogne, S., Myklebost, O., Gausepohl, H., & Stanley, K. K. (1988) · The EMBO Journal · doi:10.1002/j.1460-2075.1988.tb03306.x · Cited by 959
Qian, Z., Gilbert, M. E., Colicos, M. A., Kandel, E. R., & Kuhl, D. (1993) · Nature · doi:10.1038/361453a0 · Cited by 870
Cited by
Amyloid Beta: Structure, Biology and Structure-Based Therapeutic Development
Chen, G.-F., Xu, T.-H., Yan, Y., Zhou, Y.-R., Jiang, Y., Melcher, K., & Xu, H. E. (2017) · Acta Pharmacologica Sinica · doi:10.1038/aps.2017.28 · Cited by 1,965
Blood-brain barrier tight junction permeability and ischemic stroke
Sandoval, K. E., & Witt, K. A. (2008) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.08.005 · Cited by 964
Lillis, A. P., Van Duyn, L. B., Murphy-Ullrich, J. E., & Strickland, D. K. (2008) · Physiological Reviews · doi:10.1152/physrev.00033.2007 · Cited by 669
Self-citationPardridge, W. M. (2007) · Pharmaceutical Research · doi:10.1007/s11095-007-9324-2 · Cited by 447
Liu, J., Jin, X., Liu, K. J., & Liu, W. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.6409-11.2012 · Cited by 434
Metadata
- Authors
- Yepes, M., Sandkvist, M., Moore, E. G., Bugge, T. H., Strickland, D. K., & Lawrence, D. A.
- Venue
- Journal of Clinical Investigation
- Published
- 2003-11-15
- Volume
- 112
- Issue
- 10
- Pages
- 1533-1540
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2133045741
- Cited by
- 566
- References
- 49
- FWCI
- 15.45
- Type
- journal article
- Language
- en
- Open access
- bronze
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
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Tissue-type plasminogen activator induces opening of the blood-brain barrier via the LDL receptor–related protein. https://app.cochat.ai/papers/10.1172/jci19212
- The paper
- Yepes, M., Sandkvist, M., Moore, E. G., Bugge, T. H., Strickland, D. K., & Lawrence, D. A. (2003). Tissue-type plasminogen activator induces opening of the blood-brain barrier via the LDL receptor–related protein. Journal of Clinical Investigation. https://doi.org/10.1172/jci19212
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
