Evidence map›Paper›PMID 26243225›Full record

ArticleStroke2015

Rosiglitazone Promotes White Matter Integrity and Long-Term Functional Recovery After Focal Cerebral Ischemia.

Lijuan Han, Wei Cai, Leilei Mao, Jia Liu, Peiying Li, Rehana K Leak, Yun Xu, Xiaoming Hu, Jun Chen

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

Article in Stroke, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.

0numbers the graph read from it
0cells of the map it votes in
99citing papers in PubMed
6.2field-weighted citation impact, top 3% 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

99 citing papers in PubMed, 151 citations in OpenAlex.

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  9. Targeting angiogenesis and white matter repair for enhanced functional recovery after acute ischemic stroke: A focus on the roles of glial cells.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
    Review
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  18. The Roles of RhoA/ROCK/NF-κB Pathway in Microglia Polarization Following Ischemic Stroke.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024
    Review
  19. Article
  20. Article

39 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

9 authors at 4 institutions in 2 countries.

Lijuan HanFrom the Department of Neurology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, P.R. China (L.H., Y.X.); Center of Cerebrovascular Disease Research, Department of Neurology, University of Pittsburgh School of Medicine, PA (L.H., W.C., L.M., X.H., J.C.); State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, Fudan University, Shanghai, China (J.L., P.L., X.H., J.C.); Department of Neurology, Multiple Sclerosis Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China (W.C.); Division of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA (R.K.L.); and Geriatric Research, Educational and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA (X.H., J.C.).
Wei CaiFrom the Department of Neurology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, P.R. China (L.H., Y.X.); Center of Cerebrovascular Disease Research, Department of Neurology, University of Pittsburgh School of Medicine, PA (L.H., W.C., L.M., X.H., J.C.); State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, Fudan University, Shanghai, China (J.L., P.L., X.H., J.C.); Department of Neurology, Multiple Sclerosis Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China (W.C.); Division of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA (R.K.L.); and Geriatric Research, Educational and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA (X.H., J.C.).
Leilei MaoFrom the Department of Neurology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, P.R. China (L.H., Y.X.); Center of Cerebrovascular Disease Research, Department of Neurology, University of Pittsburgh School of Medicine, PA (L.H., W.C., L.M., X.H., J.C.); State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, Fudan University, Shanghai, China (J.L., P.L., X.H., J.C.); Department of Neurology, Multiple Sclerosis Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China (W.C.); Division of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA (R.K.L.); and Geriatric Research, Educational and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA (X.H., J.C.).
Jia LiuFrom the Department of Neurology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, P.R. China (L.H., Y.X.); Center of Cerebrovascular Disease Research, Department of Neurology, University of Pittsburgh School of Medicine, PA (L.H., W.C., L.M., X.H., J.C.); State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, Fudan University, Shanghai, China (J.L., P.L., X.H., J.C.); Department of Neurology, Multiple Sclerosis Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China (W.C.); Division of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA (R.K.L.); and Geriatric Research, Educational and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA (X.H., J.C.).
Peiying LiFrom the Department of Neurology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, P.R. China (L.H., Y.X.); Center of Cerebrovascular Disease Research, Department of Neurology, University of Pittsburgh School of Medicine, PA (L.H., W.C., L.M., X.H., J.C.); State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, Fudan University, Shanghai, China (J.L., P.L., X.H., J.C.); Department of Neurology, Multiple Sclerosis Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China (W.C.); Division of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA (R.K.L.); and Geriatric Research, Educational and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA (X.H., J.C.).
Rehana K LeakFrom the Department of Neurology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, P.R. China (L.H., Y.X.); Center of Cerebrovascular Disease Research, Department of Neurology, University of Pittsburgh School of Medicine, PA (L.H., W.C., L.M., X.H., J.C.); State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, Fudan University, Shanghai, China (J.L., P.L., X.H., J.C.); Department of Neurology, Multiple Sclerosis Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China (W.C.); Division of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA (R.K.L.); and Geriatric Research, Educational and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA (X.H., J.C.).
Yun XuFrom the Department of Neurology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, P.R. China (L.H., Y.X.); Center of Cerebrovascular Disease Research, Department of Neurology, University of Pittsburgh School of Medicine, PA (L.H., W.C., L.M., X.H., J.C.); State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, Fudan University, Shanghai, China (J.L., P.L., X.H., J.C.); Department of Neurology, Multiple Sclerosis Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China (W.C.); Division of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA (R.K.L.); and Geriatric Research, Educational and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA (X.H., J.C.). chenj2@upmc.edu xuyun20042001@aliyun.com.
Xiaoming HuFrom the Department of Neurology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, P.R. China (L.H., Y.X.); Center of Cerebrovascular Disease Research, Department of Neurology, University of Pittsburgh School of Medicine, PA (L.H., W.C., L.M., X.H., J.C.); State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, Fudan University, Shanghai, China (J.L., P.L., X.H., J.C.); Department of Neurology, Multiple Sclerosis Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China (W.C.); Division of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA (R.K.L.); and Geriatric Research, Educational and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA (X.H., J.C.).
Jun ChenFrom the Department of Neurology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, P.R. China (L.H., Y.X.); Center of Cerebrovascular Disease Research, Department of Neurology, University of Pittsburgh School of Medicine, PA (L.H., W.C., L.M., X.H., J.C.); State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, Fudan University, Shanghai, China (J.L., P.L., X.H., J.C.); Department of Neurology, Multiple Sclerosis Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China (W.C.); Division of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA (R.K.L.); and Geriatric Research, Educational and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA (X.H., J.C.). chenj2@upmc.edu xuyun20042001@aliyun.com.
Duquesne University · USSun Yat-sen University · CNThird Affiliated Hospital of Sun Yat-sen University · CNNanjing Drum Tower Hospital · CN

Funding

INDUCIBLE DNA REPAIR IN CEREBRAL ISCHEMIAR01NS036736 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BENNETT, MICHAEL V L, GRAHAM, STEVEN H · 1997 to 2021
$5.4M
Neuroprotection in Models of Cerebral IschemiaR01NS045048 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHEN, JUN · 2003 to 2015
$3.1M
Mechanisms of Neurovascular Injury in Cerebral IschemiaR01NS089534 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHEN, JUN · 2014 to 2018
$1.7M
Immunomodulation of white matter integrity after strokeR01NS092618 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI HU, XIAOMING · 2015 to 2020
$1.7M
White matter restoration and functional recovery after experimental strokeR01NS095671 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHEN, JUN · 2015 to 2020
$1.7M
Molecular therapies to enhance brain recovery after experimental strokeI01RX000420 · VA · VETERANS HEALTH ADMINISTRATION · PI CHEN, JUN · 2012 to 2014
–
NINDS NIH HHS NS036736NINDS NIH HHS NS045048NINDS NIH HHS NS089534NINDS NIH HHS NS092618NINDS NIH HHS NS095671NINDS NIH HHS R01 NS036736NINDS NIH HHS R01 NS045048NINDS NIH HHS R01 NS089534NINDS NIH HHS R01 NS092618NINDS NIH HHS R01 NS095671RRD VA I01 RX000420
6 · The paper itself

Abstract

background and purposeOligodendrogenesis is essential for white matter repair after stroke. Although agonists of peroxisome proliferator-activated receptors γ confer neuroprotection in models of cerebral ischemia, it is not known whether this effect extends to white matter protection. This study tested the hypothesis that the peroxisome proliferator-activated receptors γ agonist rosiglitazone enhances oligodendrogenesis and improves long-term white matter integrity after ischemia/reperfusion.

methodsMale adult C57/BL6 mice (25-30 g) were subjected to 60-minute middle cerebral artery occlusion and reperfusion. Rosiglitazone (3 mg/kg) was injected intraperitoneally once daily for 14 days beginning 2 hours after reperfusion. Sensorimotor and cognitive functions were evaluated ≤21 days after middle cerebral artery occlusion. Immunostaining was used to assess infarct volume, myelin loss, and microglial activation. Bromodeoxyuridine (BrdU) was injected for measurements of proliferating NG2(+) oligodendrocyte precursor cells (OPCs) and newly generated adenomatous polyposis coli(+) oligodendrocytes. Mixed glial cultures were used to confirm the effect of rosiglitazone on oligodendrocyte differentiation and microglial polarization.

resultsRosiglitazone significantly reduced brain tissue loss, ameliorated white matter injury, and improved sensorimotor and cognitive functions for at least 21 days after middle cerebral artery occlusion. Rosiglitazone enhanced OPC proliferation and increased the numbers of newly generated mature oligodendrocytes after middle cerebral artery occlusion. Rosiglitazone treatment also reduced the numbers of Iba1(+)/CD16(+) M1 microglia and increased the numbers of Iba1(+)/CD206(+) M2 microglia after stroke. Glial culture experiments confirmed that rosiglitazone promoted oligodendrocyte differentiation, perhaps by promoting microglial M2 polarization.

conclusionsRosiglitazone treatment improves long-term white matter integrity after cerebral ischemia, at least, in part, by promoting oligodendrogenesis and facilitating microglial polarization toward the beneficial M2 phenotype.

Indexed as

AnimalsBrain IschemiaDisease Models, AnimalInfarction, Middle Cerebral ArteryMaleMiceMice, Inbred C57BLMicrogliaOligodendrogliaPPAR gammaRecovery of FunctionReperfusionRosiglitazoneThiazolidinedionesWhite MatterPPAR gammaRosiglitazoneThiazolidinedionesbromodeoxyuridineinflammationpolarizationstrokewhite matter

Identifiers

PMID26243225
PMCPMC4615602
OpenAlexW1937277400

What OpenQuestion holds

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Read underepoch 390

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.