Evidence map›Paper›PMID 40045320›Full record

ArticleJournal of neuroinflammation2025

Development of cerebral microhemorrhages in a mouse model of hypertension.

Danny F Xie, Chuo Fang, Christian Crouzet, Yu-Han Hung, Adrian Vallejo, Donghy Lee, Jihua Liu, Han Liu, Suhrith Muvvala, Annlia Paganini-Hill and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neuroinflammation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Roles of Microglia in Cerebral Small Vessel Disease.CNS neuroscience & therapeutics · 2026
    Review
  2. Article
  3. Review
  4. Article
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Danny F Xie *Beckman Laser Institute and Medical Clinic, University of California, Irvine, CA, USA.
Chuo Fang *Department of Neurology, University of California, Irvine, CA, USA.
Christian CrouzetBeckman Laser Institute and Medical Clinic, University of California, Irvine, CA, USA.
Yu-Han HungDepartment of Neurology, University of California, Irvine, CA, USA.
Adrian VallejoDepartment of Neurology, University of California, Irvine, CA, USA.
Donghy LeeDepartment of Neurology, University of California, Irvine, CA, USA.
Jihua LiuInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
Han LiuDepartment of Medicine, Division of Nephrology, University of California, Irvine, CA, USA.
Suhrith MuvvalaBeckman Laser Institute and Medical Clinic, University of California, Irvine, CA, USA.
Annlia Paganini-HillBeckman Laser Institute and Medical Clinic, University of California, Irvine, CA, USA.
Wei Ling LauDepartment of Medicine, Division of Nephrology, University of California, Irvine, CA, USA.
David H CribbsInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
Bernard ChoiBeckman Laser Institute and Medical Clinic, University of California, Irvine, CA, USA. choib@uci.edu.
Mark FisherBeckman Laser Institute and Medical Clinic, University of California, Irvine, CA, USA. mfisher@hs.uci.edu.

Funding

Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Melanie Funes · 1994 to 2026
$57.9M
Uncover Strategies Used By Biological SystemsP50GM076516 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI NIE, QING · 2007 to 2016
$25.1M
HEMORHOLOGICAL FACTORS IN CEREBRAL ISCHEMIAR01NS020989 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CRIBBS, DAVID HASTINGS, FISHER, MARK J · 1985 to 2022
$9.1M
NRSA Training CoreTL1TR001415 · NCATS · UNIVERSITY OF CALIFORNIA-IRVINE · PI CAIOZZO, VINCENT JAMES, HEAD, ELIZABETH · 2015 to 2023
$4.2M
Gut-Derived Toxins and Brain Microbleeds in Chronic Kidney DiseaseR01NS113337 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI LAU, WEI LING · 2020 to 2024
$1.7M
Acquisition of nonlinear optical microscopy platform for advanced tissue imagingS10OD028698 · OD · UNIVERSITY OF CALIFORNIA-IRVINE · PI POTMA, ERIC OLAF · 2020 to 2020
$1.6M
Hypertensive Mechanisms of Cerebral MicrobleedsR21NS111984 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI CRIBBS, DAVID HASTINGS, FISHER, MARK J · 2019 to 2019
$425k
Multiscale optical characterization of cerebrovascular structure, function and oxygen utilization in a novel mouse model of sporadic Alzheimer's diseaseR21AG066000 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI CHOI, BERNARD · 2020 to 2020
$411k
BrightFocus Foundation A2022005FNCATS NIH HHS TL1 TR001415NCI NIH HHS P30 CA062203NIA NIH HHS R21 AG066000NIGMS NIH HHS P50 GM076516NIH HHS NS020989, NS111984, AG066000, 5TL1TR001415NIH HHS S10 OD028698NINDS NIH HHS R01 NS020989NINDS NIH HHS R01 NS113337NINDS NIH HHS R21 NS111984
6 · The paper itself

Abstract

Cerebral microhemorrhages (CMH) are the pathological substrate for MRI-demonstrable cerebral microbleeds, which are associated with cognitive impairment and stroke. Aging and hypertension are the main risk factors for CMH. In this study, we investigated the development of CMH in a mouse model of aging and hypertension. Hypertension was induced in aged (17-month-old) female and male C57BL/6J mice via angiotensin II (Ang II), a potent vasoconstrictor. We investigated the vascular origin of CMH using three-dimensional images of 1-mm thick brain sections. We examined Ang II-induced CMH formation with and without telmisartan, an Ang II type 1 receptor (AT1R) blocker. To evaluate the effect of microglia and perivascular macrophages on CMH formation, mice were treated with PLX3397, a selective colony-stimulating factor 1 receptor (CSF1R) inhibitor, to achieve microglial and macrophage depletion. Iba-1 and CD206 labeling were used to study the relative contributions of microglia and macrophages, respectively, on CMH formation. CMH quantification was performed with analysis of histological sections labeled with Prussian blue. Vessels surrounding CMH were primarily of capillary size range (< 10 μm in diameter). Ang II-infused mice exhibited elevated blood pressure (p < 0.0001) and CMH burden (p < 0.001). CMH burden was significantly correlated with mean arterial pressure in mice with and without Ang II (r = 0.52, p < 0.05). Ang II infusion significantly increased Iba-1 immunoreactivity (p < 0.0001), and CMH burden was significantly correlated with Iba-1 in mice with and without Ang II (r = 0.32, p < 0.05). Telmisartan prevented elevation of blood pressure due to Ang II infusion and blocked Ang II-induced CMH formation without affecting Iba-1 immunoreactivity. PLX3397 treatment reduced Iba-1 immunoreactivity in Ang II-infused mice (p < 0.001) and blocked Ang II-induced CMH (p < 0.0001). No significant association between CMH burden and CD206 reactivity was observed. Our findings demonstrate Ang II infusion increases CMH burden. CMH in this model appear to be capillary-derived and Ang II-induced CMH are largely mediated by blood pressure. In addition, microglial activation may represent an alternate pathway for CMH formation. These observations emphasize the continuing importance of blood pressure control and the role of microglia in hemorrhagic cerebral microvascular disease.

Indexed as

Cerebral HemorrhageHypertensionAminopyridinesAngiotensin IIAngiotensin II Type 1 Receptor BlockersAnimalsBenzimidazolesBenzoatesCalcium-Binding ProteinsDisease Models, AnimalFemaleLectins, C-TypeMacrophagesMaleMannose-Binding LectinsMannose ReceptorAif1 protein, mouseAminopyridinesAngiotensin IIAngiotensin II Type 1 Receptor BlockersBenzimidazolesBenzoatesCalcium-Binding ProteinsLectins, C-TypeMannose-Binding LectinsMannose ReceptorMicrofilament ProteinspexidartinibPyrrolesReceptors, Cell SurfaceTelmisartanAgingAngiotensin IICerebral microbleedsCerebral microhemorrhagesHypertensionMicroglial activationTelmisartan

Identifiers

PMID40045320
PMCPMC11881401

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.