Evidence map›Paper›PMID 30734229›Full record

ArticleMolecular neurobiology2019

Microglial Depletion with Clodronate Liposomes Increases Proinflammatory Cytokine Levels, Induces Astrocyte Activation, and Damages Blood Vessel Integrity.

Xiaoning Han, Qian Li, Xi Lan, Leena El-Mufti, Honglei Ren, Jian Wang

Abstract read
In one paragraph

Article in Molecular neurobiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
4.7field-weighted citation impact, top 5% of its field
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

63 citing papers in PubMed, 83 citations in OpenAlex.

  1. Gut microbes · 2026
    Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. Review
  18. Review
  19. Microglia at the blood brain barrier in health and disease.Frontiers in cellular neuroscience · 2024
    Review
  20. Review

3 more citing papers are in PubMed but not listed here.

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

6 authors at 1 institution in 2 countries.

Xiaoning HanDepartment of Anesthesiology/Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, 21205, USA.
Qian LiDepartment of Anesthesiology/Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, 21205, USA.
Xi LanDepartment of Anesthesiology/Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, 21205, USA.
Leena El-MuftiDepartment of Anesthesiology/Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, 21205, USA.
Honglei RenDepartment of Anesthesiology/Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, 21205, USA.
Jian WangDepartment of Anesthesiology/Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, 21205, USA. jwang79@jhmi.edu.ORCID http://orcid.org/0000-0003-2291-640X
Johns Hopkins University · US

Funding

Wnt Signaling in StrokeR01NS105894 · NINDS · JOHNS HOPKINS UNIVERSITY · PI KOEHLER, RAYMOND CHARLES · 2018 to 2022
$2.3M
Microglia/macrophage polarization after intracerebral hemorrhageR01NS102583 · NINDS · JOHNS HOPKINS UNIVERSITY · PI KOEHLER, RAYMOND CHARLES · 2018 to 2021
$1.8M
American Heart Association 16SDG30980031American Heart Association 17GRNT33660766American Heart Association-American Stroke Association 17POST33660191NIH HHS R56NS096549; R01NS102583; R01NS105894NINDS NIH HHS R01 NS102583NINDS NIH HHS R01 NS105894
6 · The paper itself

Abstract

Investigators are increasingly interested in using microglial depletion to study the role of microglia under pathologic conditions. Liposome-encapsulated clodronate is commonly used to eliminate macrophage populations because it causes functionally irreversible inhibition and apoptosis once phagocytized by macrophages. Recent studies have shown that microglia can be depleted in disease models by injecting clodronate liposomes into the brain parenchyma. However, it is unclear whether intracerebral administration of clodronate liposomes is a practical method of eliminating microglia under physiologic conditions or whether microglial depletion induces damage to other brain cells. In this study, injecting 1 μL of clodronate liposomes (7 μg/μL) into the striatum of mice caused ablation of microglia at 1 day that persisted for 3 days. Microglia reappeared in the boundary regions of microglia elimination after 5 days. Importantly, we observed an increase in proinflammatory cytokine levels and an increase in neural/glial antigen 2 and glial fibrillary acidic protein expression in the perilesional region. In contrast, expression levels of myelin basic protein, microtubule-associated protein 2, and postsynaptic protein-95 decreased in the periphery of regions where microglia were depleted. Moreover, clodronate liposome administration decreased the density and integrity of blood vessels in the perilesional regions. In cultured primary neurons, clodronate liposome exposure also attenuated ATP synthesis. Together, these findings suggest that intracerebral administration of clodronate liposomes into brain parenchyma can deplete microglia, but can also damage other brain cells and blood vessel integrity.

Indexed as

AnimalsAstrocytesBlood VesselsClodronic AcidCytokinesInflammation MediatorsLiposomesMaleMice, Inbred C57BLMicrogliaNeostriatumNerve DegenerationNeurogliaUp-RegulationClodronic AcidCytokinesInflammation MediatorsLiposomesClodronate liposomesInflammationMicroglial depletion

Identifiers

PMID30734229
PMCPMC6684378
OpenAlexW2914309526

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.