Evidence map›Paper›PMID 30528430›Full record

ArticleCell2019

Methotrexate Chemotherapy Induces Persistent Tri-glial Dysregulation that Underlies Chemotherapy-Related Cognitive Impairment.

Erin M Gibson, Surya Nagaraja, Alfonso Ocampo, Lydia T Tam, Lauren S Wood, Praveen N Pallegar, Jacob J Greene, Anna C Geraghty, Andrea K Goldstein, Lijun Ni and 5 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 226 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
226citing papers in PubMed, 2 pooled it
22.4field-weighted citation impact, top 1% 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

226 citing papers in PubMed, 2 syntheses or guidelines pooled it, 340 citations in OpenAlex.

  1. Pooled it
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  11. Cancer treatment-related cognitive impairment.Neuro-oncology advances · 2026
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166 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 1 country.

Erin M GibsonDepartment of Neurology and Neurological Sciences, Stanford University, Palo Alto, CA 94305, USA.
Surya NagarajaDepartment of Neurology and Neurological Sciences, Stanford University, Palo Alto, CA 94305, USA.
Alfonso OcampoDepartment of Neurology and Neurological Sciences, Stanford University, Palo Alto, CA 94305, USA.
Lydia T TamDepartment of Neurology and Neurological Sciences, Stanford University, Palo Alto, CA 94305, USA.
Lauren S WoodDepartment of Neurology and Neurological Sciences, Stanford University, Palo Alto, CA 94305, USA.
Praveen N PallegarDepartment of Neurology and Neurological Sciences, Stanford University, Palo Alto, CA 94305, USA.
Jacob J GreeneDepartment of Neurology and Neurological Sciences, Stanford University, Palo Alto, CA 94305, USA.
Anna C GeraghtyDepartment of Neurology and Neurological Sciences, Stanford University, Palo Alto, CA 94305, USA.
Andrea K GoldsteinDepartment of Neurology and Neurological Sciences, Stanford University, Palo Alto, CA 94305, USA.
Lijun NiDepartment of Neurology and Neurological Sciences, Stanford University, Palo Alto, CA 94305, USA.
Pamelyn J WooDepartment of Neurology and Neurological Sciences, Stanford University, Palo Alto, CA 94305, USA.
Ben A BarresDepartment of Neurobiology, Stanford University, Palo Alto, CA 94305, USA.
Shane LiddelowDepartment of Neurobiology, Stanford University, Palo Alto, CA 94305, USA; Department of Neuroscience and Physiology, NYU Neuroscience Institute, New York University School of Medicine, New York, NY 10016, USA.
Hannes VogelDepartment of Pathology, Stanford University, Palo Alto, CA 94305, USA.
Michelle MonjeDepartment of Neurology and Neurological Sciences, Stanford University, Palo Alto, CA 94305, USA; Department of Pathology, Stanford University, Palo Alto, CA 94305, USA; Department of Pediatrics, Stanford University, Palo Alto, CA 94305, USA; Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Palo Alto, CA 94305, USA. Electronic address: mmonje@stanford.edu.
Stanford University · USCalifornia Institute for Regenerative Medicine · USNew York University · US

Funding

Stanford Center for Clinical and Translational Education and Research (SCCTER)UL1UL1RR025744 · NCRR · STANFORD UNIVERSITY · PI GREENBERG, HARRY BERNARD · 2008 to 2011
$22.4M
Neuronal activity-regulated mechanisms of glioma growthR01NS092597 · NINDS · STANFORD UNIVERSITY · PI MONJE-DEISSEROTH, MICHELLE · 2016 to 2021
$2.1M
NCRR NIH HHS UL1 RR025744NINDS NIH HHS R01 NS092597
6 · The paper itself

Abstract

Chemotherapy results in a frequent yet poorly understood syndrome of long-term neurological deficits. Neural precursor cell dysfunction and white matter dysfunction are thought to contribute to this debilitating syndrome. Here, we demonstrate persistent depletion of oligodendrocyte lineage cells in humans who received chemotherapy. Developing a mouse model of methotrexate chemotherapy-induced neurological dysfunction, we find a similar depletion of white matter OPCs, increased but incomplete OPC differentiation, and a persistent deficit in myelination. OPCs from chemotherapy-naive mice similarly exhibit increased differentiation when transplanted into the microenvironment of previously methotrexate-exposed brains, indicating an underlying microenvironmental perturbation. Methotrexate results in persistent activation of microglia and subsequent astrocyte activation that is dependent on inflammatory microglia. Microglial depletion normalizes oligodendroglial lineage dynamics, myelin microstructure, and cognitive behavior after methotrexate chemotherapy. These findings indicate that methotrexate chemotherapy exposure is associated with persistent tri-glial dysregulation and identify inflammatory microglia as a therapeutic target to abrogate chemotherapy-related cognitive impairment. VIDEO ABSTRACT.

Indexed as

AnimalsBrainCell DifferentiationCell LineageCognitive DysfunctionDisease Models, AnimalDrug-Related Side Effects and Adverse ReactionsDrug TherapyHumansMethotrexateMiceMicrogliaMyelin SheathNerve Fibers, MyelinatedNeurogenesisNeurogliaMethotrexateastrocytechemobrainchemotherapychemotherapy-related cognitive impairmentmicrogliamyelinoligodendrocyteOPC

Identifiers

PMID30528430
PMCPMC6329664
OpenAlexW2903050755

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.