Evidence map›Paper›PMID 24916903›Full record

Trial reportStroke2014

Neuronal production of lipocalin-2 as a help-me signal for glial activation.

Changhong Xing, Xiaoshu Wang, Chongjie Cheng, Joan Montaner, Emiri Mandeville, Wendy Leung, Klaus van Leyen, Josephine Lok, Xiaoying Wang, Eng H Lo

Open access · bronzeAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Stroke, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.

0numbers the graph read from it
0cells of the map it votes in
102citing papers in PubMed
5.2field-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

102 citing papers in PubMed, 167 citations in OpenAlex.

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  18. Repetitive Administration of Low-Dose Lipopolysaccharide Improves Repeated Social Defeat Stress-Induced Behavioral Abnormalities and Aberrant Immune Response.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024
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42 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

10 authors at 1 institution in 1 country.

Changhong XingFrom the Departments of Radiology, Neurology, and Pediatrics, Massachusetts General Hospital, Harvard Medical School, Charlestown (C.X., Xiaoshu Wang, C.C., E.M., W.L., K.v.L., J.L., Xiaoying Wang, E.H.L.); Department of Neurosurgery, First Affiliated Hospital, Chongqing Medical University, Chongqing, China (Xiaoshu Wang, C.C.); and Neurovascular Research Laboratory, Vall d'Hebron University Hospital Research Institute, Barcelona, Spain (J.M.). Lo@helix.mgh.harvard.edu xing.changhong@mgh.harvard.edu.
Xiaoshu WangFrom the Departments of Radiology, Neurology, and Pediatrics, Massachusetts General Hospital, Harvard Medical School, Charlestown (C.X., Xiaoshu Wang, C.C., E.M., W.L., K.v.L., J.L., Xiaoying Wang, E.H.L.); Department of Neurosurgery, First Affiliated Hospital, Chongqing Medical University, Chongqing, China (Xiaoshu Wang, C.C.); and Neurovascular Research Laboratory, Vall d'Hebron University Hospital Research Institute, Barcelona, Spain (J.M.).
Chongjie ChengFrom the Departments of Radiology, Neurology, and Pediatrics, Massachusetts General Hospital, Harvard Medical School, Charlestown (C.X., Xiaoshu Wang, C.C., E.M., W.L., K.v.L., J.L., Xiaoying Wang, E.H.L.); Department of Neurosurgery, First Affiliated Hospital, Chongqing Medical University, Chongqing, China (Xiaoshu Wang, C.C.); and Neurovascular Research Laboratory, Vall d'Hebron University Hospital Research Institute, Barcelona, Spain (J.M.).
Joan MontanerFrom the Departments of Radiology, Neurology, and Pediatrics, Massachusetts General Hospital, Harvard Medical School, Charlestown (C.X., Xiaoshu Wang, C.C., E.M., W.L., K.v.L., J.L., Xiaoying Wang, E.H.L.); Department of Neurosurgery, First Affiliated Hospital, Chongqing Medical University, Chongqing, China (Xiaoshu Wang, C.C.); and Neurovascular Research Laboratory, Vall d'Hebron University Hospital Research Institute, Barcelona, Spain (J.M.).
Emiri MandevilleFrom the Departments of Radiology, Neurology, and Pediatrics, Massachusetts General Hospital, Harvard Medical School, Charlestown (C.X., Xiaoshu Wang, C.C., E.M., W.L., K.v.L., J.L., Xiaoying Wang, E.H.L.); Department of Neurosurgery, First Affiliated Hospital, Chongqing Medical University, Chongqing, China (Xiaoshu Wang, C.C.); and Neurovascular Research Laboratory, Vall d'Hebron University Hospital Research Institute, Barcelona, Spain (J.M.).
Wendy LeungFrom the Departments of Radiology, Neurology, and Pediatrics, Massachusetts General Hospital, Harvard Medical School, Charlestown (C.X., Xiaoshu Wang, C.C., E.M., W.L., K.v.L., J.L., Xiaoying Wang, E.H.L.); Department of Neurosurgery, First Affiliated Hospital, Chongqing Medical University, Chongqing, China (Xiaoshu Wang, C.C.); and Neurovascular Research Laboratory, Vall d'Hebron University Hospital Research Institute, Barcelona, Spain (J.M.).
Klaus van LeyenFrom the Departments of Radiology, Neurology, and Pediatrics, Massachusetts General Hospital, Harvard Medical School, Charlestown (C.X., Xiaoshu Wang, C.C., E.M., W.L., K.v.L., J.L., Xiaoying Wang, E.H.L.); Department of Neurosurgery, First Affiliated Hospital, Chongqing Medical University, Chongqing, China (Xiaoshu Wang, C.C.); and Neurovascular Research Laboratory, Vall d'Hebron University Hospital Research Institute, Barcelona, Spain (J.M.).
Josephine LokFrom the Departments of Radiology, Neurology, and Pediatrics, Massachusetts General Hospital, Harvard Medical School, Charlestown (C.X., Xiaoshu Wang, C.C., E.M., W.L., K.v.L., J.L., Xiaoying Wang, E.H.L.); Department of Neurosurgery, First Affiliated Hospital, Chongqing Medical University, Chongqing, China (Xiaoshu Wang, C.C.); and Neurovascular Research Laboratory, Vall d'Hebron University Hospital Research Institute, Barcelona, Spain (J.M.).
Xiaoying WangFrom the Departments of Radiology, Neurology, and Pediatrics, Massachusetts General Hospital, Harvard Medical School, Charlestown (C.X., Xiaoshu Wang, C.C., E.M., W.L., K.v.L., J.L., Xiaoying Wang, E.H.L.); Department of Neurosurgery, First Affiliated Hospital, Chongqing Medical University, Chongqing, China (Xiaoshu Wang, C.C.); and Neurovascular Research Laboratory, Vall d'Hebron University Hospital Research Institute, Barcelona, Spain (J.M.).
Eng H LoFrom the Departments of Radiology, Neurology, and Pediatrics, Massachusetts General Hospital, Harvard Medical School, Charlestown (C.X., Xiaoshu Wang, C.C., E.M., W.L., K.v.L., J.L., Xiaoying Wang, E.H.L.); Department of Neurosurgery, First Affiliated Hospital, Chongqing Medical University, Chongqing, China (Xiaoshu Wang, C.C.); and Neurovascular Research Laboratory, Vall d'Hebron University Hospital Research Institute, Barcelona, Spain (J.M.). Lo@helix.mgh.harvard.edu xing.changhong@mgh.harvard.edu.
Chongqing Medical University · CN

Funding

Targeting ROCK for Neurogliovascular Plasticity & Remodeling After StrokeP01NS055104 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI LO, ENG H. · 2007 to 2018
$13.3M
Biphasic mechanisms of injury and repair in stroke therapyR37NS037074 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI LO, ENG H. · 2008 to 2015
$3.2M
Thrombolysis Profiles in tPA ResponseR01NS093415 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI LO, ENG H., NING, MINGMING · 2015 to 2019
$1.9M
Astrocyte-endothelial crosstalk after cerebral ischemia and hemorrhageR01NS076694 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI LO, ENG H. · 2011 to 2015
$1.9M
Neuregulin-1 and Neurovascular ProtectionK08NS057339 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI LOK, JOSEPHINE MUN-YEE · 2009 to 2013
$890k
NINDS NIH HHS K08 NS057339NINDS NIH HHS P01 NS055104NINDS NIH HHS R01 NS076694NINDS NIH HHS R01 NS093415NINDS NIH HHS R37 NS037074
6 · The paper itself

Abstract

background and purposeWe explored the hypothesis that injured neurons release lipocalin-2 as a help me signal.

methodsIn vivo lipocalin-2 responses were assessed in rat focal cerebral ischemia and human stroke brain samples using a combination of ELISA and immunostaining. In vitro, microglia and astrocytes were exposed to lipocalin-2, and various markers and assays of glial activation were quantified. Functional relevance of neuron-to-glia lipocalin-2 signaling was examined by transferring conditioned media from lipocalin-2-activated microglia and astrocytes onto neurons to see whether activated glia could protect neurons against oxygen-glucose deprivation and promote neuroplasticity.

resultsIn human stroke samples and rat cerebral ischemia, neuronal expression of lipocalin-2 was significantly increased. In primary cell cultures, exposing microglia and astrocytes to lipocalin-2 resulted in glial activation. In microglia, lipocalin-2 converted resting ramified shapes into a long-rod morphology with reduced branching, increased interleukin-10 release, and enhanced phagocytosis. In astrocytes, lipocalin-2 upregulated glial fibrillary acid protein, brain-derived neurotropic factor, and thrombospondin-1. Conditioned media from lipocalin-2-treated astrocytes upregulated synaptotagmin, and conditioned media from lipocalin-2-treated microglia upregulated synaptophysin and post-synaptic density 95 (PSD95) and protected neurons against oxygen-glucose deprivation.

conclusionsThese findings provide proof of concept that lipocalin-2 is released by injured neurons as a help me distress signal that activates microglia and astrocytes into potentially prorecovery phenotypes.

Indexed as

Acute-Phase ProteinsAgedAnimalsAstrocytesBiomarkersBrain IschemiaCerebral CortexFemaleHumansLipocalin-2LipocalinsMaleMicrogliaNeuronal PlasticityNeuronsPhenotypeAcute-Phase ProteinsBiomarkersLCN2 protein, humanLcn2 protein, ratLipocalin-2LipocalinsProto-Oncogene Proteinsastrocyteslipocalinsmicroglianeurons

Identifiers

PMID24916903
PMCPMC4122238
OpenAlexW2060668038

What OpenQuestion holds

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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.