The DOI matches its Crossref record; 63 of the 63 references it cites were found in a registry or an index.
Traumatic Brain Injury Causes Endothelial Dysfunction in the Systemic Microcirculation through Arginase-1–Dependent Uncoupling of Endothelial Nitric Oxide Synthase
Open accessAbstract
Endothelial dysfunction is a hallmark of many chronic diseases, including diabetes and long-term hypertension. We show that acute traumatic brain injury (TBI) leads to endothelial dysfunction in rat mesenteric arteries. Endothelial-dependent dilation was greatly diminished 24 h after TBI because of impaired nitric oxide (NO) production. The activity of arginase, which competes with endothelial NO synthase (eNOS) for the common substrate l-arginine, were also significantly increased in arteries, suggesting that arginase-mediated depletion of l-arginine underlies diminished NO production. Consistent with this, substrate restoration by exogenous application of l-arginine or inhibition of arginase recovered endothelial function. Moreover, evidence for increased reactive oxygen species production, a consequence of l-arginine starvation-dependent eNOS uncoupling, was detected in endothelium and plasma. Collectively, our findings demonstrate endothelial dysfunction in a remote vascular bed after TBI, manifesting as impaired endothelial-dependent vasodilation, with increased arginase activity, decreased generation of NO, and increased O2- production. We conclude that blood vessels have a “molecular memory” of neurotrauma, 24 h after injury, because of functional changes in vascular endothelial cells; these effects are pertinent to understanding the systemic inflammatory response that occurs after TBI even in the absence of polytrauma.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The text we found for this paper looks like another document, so the self-check wasn’t run.
Citations
Cites
Nitric oxide: physiology, pathophysiology, and pharmacology.
Moncada, S., Palmer, R. M., & Higgs, E. A. (1991) · Pharmacological Reviews · doi:10.1016/s0031-6997(25)06663-3 · Cited by 15,525
Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor
Palmer, R. M. J., Ferrige, A. G., & Moncada, S. (1987) · Nature · doi:10.1038/327524a0 · Cited by 10,704
How mitochondria produce reactive oxygen species
Murphy, M. P. (2009) · Biochemical Journal · doi:10.1042/bj20081386 · Cited by 8,207
Nitric oxide synthases: regulation and function
Forstermann, U., & Sessa, W. C. (2012) · European Heart Journal · doi:10.1093/eurheartj/ehr304 · Cited by 4,409
Arginine metabolism: nitric oxide and beyond
WU, G., & MORRIS, S. M. (1998) · Biochemical Journal · doi:10.1042/bj3360001 · Cited by 2,811
Rajagopalan, S., Kurz, S. D., Münzel, T. F., Tarpey, M. M., Freeman, B. Α., Griendling, K. K., & Harrison, D. G. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118623 · Cited by 2,467
Hypercholesterolemia increases endothelial superoxide anion production.
Ohara, Y., Peterson, T. E., & Harrison, D. G. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116491 · Cited by 1,765
Landmesser, U., Dikalov, S., Price, S. R., McCann, L., Fukai, T., Holland, S. M., Mitch, W. E., & Harrison, D. G. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200314172 · Cited by 1,660
Landmesser, U., Dikalov, S., Price, S. R., McCann, L. A., Fukai, T., Holland, S. M., Mitch, W. E., & Harrison, D. G. (2003) · Journal of Clinical Investigation · doi:10.1172/jci14172 · Cited by 1,652
Nitric Oxide Synthases: Properties and Catalytic Mechanism
Griffith, O. W., & Stuehr, D. J. (1995) · Annual Review of Physiology · doi:10.1146/annurev.ph.57.030195.003423 · Cited by 1,311
Flagged first, then by citations
Research works printed but not linked: 4
- Forstermann U., 2012, Eur. Heart J., 33, 837a
- Arribas S.M., 2007, Clin. Hemorheol. Microcirc., 37, 205
- Dhanakoti S.N., 1990, Am. J. Physiol., 259, E437
- 10.1172/JCI200314172 · DOI · Paper page
Cited by
Sorted by citations
Items 101–101 of 101
雷小龙, Yang, Y., Yang, X., & Tao, K. (2026) · Frontiers in Neurology · doi:10.3389/fneur.2026.1971528
Metadata
- Authors
- Villalba, N., Sackheim, A. M., Nunez, I. A., Hill-Eubanks, D. C., Nelson, M. T., Wellman, G. C., & Freeman, K.
- Affiliations
- University of Vermont (US)
- Department of Surgery, University of Vermont, Burlington, Vermont.
- Department of Pharmacology, University of Vermont, Burlington, Vermont.
- Corresponding author
- Freeman, Kalev
- Venue
- Journal of Neurotrauma
- Publisher
- SAGE Publications
- Published
- 2017-01
- Volume
- 34
- Issue
- 1
- Pages
- 192-203
- ISSN
- 0897-7151 (ISSN-L)
- 1557-9042
- PMC
- PMC5198065
- OpenAlex
- W2330581287
- Cited by
- 99
- References
- 62
- Citations by year
- 2026: 12 · 2025: 10 · 2024: 10 · 2023: 10 · 2022: 10 · 2021: 14 · 2020: 14 · 2019: 6 · 2018: 6 · 2017: 6
- FWCI
- 5.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neurotrauma (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion, other-oa)
- Funders
- National Institutes of Health (5p30gm103498-05, 1s10od017969-01)
- National Heart, Lung, and Blood Institute (R01HL044455, P01HL095488, R01HL121706, R01HL098243, UM1HL120877)
- National Institute of General Medical Sciences (P30-GM103498, K08GM098795)
- National Institute of Diabetes and Digestive and Kidney Diseases (R37DK053832)
- National Center for Research Resources (P20RR016435, P30RR032135)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Keywords
- traumatic brain injury, endothelial dysfunction, arginase-1, endothelial nitric oxide synthase uncoupling, nitric oxide production, L-arginine depletion, reactive oxygen species, endothelium-dependent vasodilation, mesenteric arteries, systemic inflammatory response
- MeSH terms
- Brain Injuries, Traumatic, Acetylcholine, Animals, Arginase, Endothelium, Vascular, Male, Microcirculation, Vasodilation, Rats, Sprague-Dawley, Rats, Nitric Oxide Synthase Type III
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
