Evidence map›Paper›PMID 33161850›Full record

ArticleStroke2021

Microglial Calcium Waves During the Hyperacute Phase of Ischemic Stroke.

Lei Liu, Kathryn N Kearns, Ilyas Eli, Khadijeh A Sharifi, Sauson Soldozy, Elizabeth W Carlson, Kyle W Scott, M Filip Sluzewski, Scott T Acton, Kenneth A Stauderman and 3 more

Open access · greenAbstract read
In one paragraph

Article in Stroke, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 9% 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

30 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Calcium Signaling in Macrophages During a Wound Response In Vivo.International journal of molecular sciences · 2026
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  13. Electrolyte Imbalance and Neurologic Injury.CNS & neurological disorders drug targets · 2024
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 2 countries.

Lei LiuDepartment of Neurological Surgery (L.L., K.N.K., K.A. Sharifi, S.S., K.W.S., M.Y.S.K., M.P., P.T.), University of Virginia Health System, Charlottesville.
Kathryn N KearnsDepartment of Neurological Surgery (L.L., K.N.K., K.A. Sharifi, S.S., K.W.S., M.Y.S.K., M.P., P.T.), University of Virginia Health System, Charlottesville.
Ilyas EliDepartment of Neurosurgery (I.E., E.W.C.), University of Utah School of Medicine, Salt Lake City.
Khadijeh A SharifiDepartment of Neurological Surgery (L.L., K.N.K., K.A. Sharifi, S.S., K.W.S., M.Y.S.K., M.P., P.T.), University of Virginia Health System, Charlottesville.
Sauson SoldozyDepartment of Neurological Surgery (L.L., K.N.K., K.A. Sharifi, S.S., K.W.S., M.Y.S.K., M.P., P.T.), University of Virginia Health System, Charlottesville.
Elizabeth W CarlsonDepartment of Neurosurgery (I.E., E.W.C.), University of Utah School of Medicine, Salt Lake City.
Kyle W ScottDepartment of Neurological Surgery (L.L., K.N.K., K.A. Sharifi, S.S., K.W.S., M.Y.S.K., M.P., P.T.), University of Virginia Health System, Charlottesville.
M Filip SluzewskiDepartment of Electrical and Computer Engineering (M.F.S., S.T.A.), University of Virginia Health System, Charlottesville.
Scott T ActonDepartment of Electrical and Computer Engineering (M.F.S., S.T.A.), University of Virginia Health System, Charlottesville.
Kenneth A StaudermanCalciMedica (K.A. Stauderman), San Diego, CA.
M Yashar S KalaniDepartment of Neurological Surgery (L.L., K.N.K., K.A. Sharifi, S.S., K.W.S., M.Y.S.K., M.P., P.T.), University of Virginia Health System, Charlottesville.
Min ParkDepartment of Neurological Surgery (L.L., K.N.K., K.A. Sharifi, S.S., K.W.S., M.Y.S.K., M.P., P.T.), University of Virginia Health System, Charlottesville.
Petr TvrdikDepartment of Neurological Surgery (L.L., K.N.K., K.A. Sharifi, S.S., K.W.S., M.Y.S.K., M.P., P.T.), University of Virginia Health System, Charlottesville.
Norwegian Womens Public Health Association · NOUniversity of Virginia Health System · USUniversity of Utah · USCalciMedica (United States) · US

Funding

Cre, Dre Dual Lineage Model for Calcium Imaging and Optogenetic ManipulationsR21OD016562 · OD · UNIVERSITY OF UTAH · PI TVRDIK, PETR · 2013 to 2014
$391k
NIH HHS R21 OD016562
6 · The paper itself

Abstract

background and purposeIschemic injury triggers multiple pathological responses in the brain tissue, including spreading depolarizations across the cerebral cortex (cortical spreading depolarizations [CSD]). Microglia have been recently shown to play a significant role in the propagation of CSD. However, the intracellular responses of myeloid cells during ischemic stroke have not been investigated.

methodsWe have studied intracellular calcium activity in cortical microglia in the stroke model of the middle cerebral artery occlusion, using the murine Polr2a-based and Cre-dependent GCaMP5 and tdTomato reporter (PC::G5-tdT). High-speed 2-photon microscopy through cranial windows was employed to record signals from genetically encoded indicators of calcium. Inflammatory stimuli and pharmacological inhibition were used to modulate microglial calcium responses in the somatosensory cortex.

resultsIn vivo imaging revealed periodical calcium activity in microglia during the hyperacute phase of ischemic stroke. This activity was more frequent during the first 6 hours after occlusion, but the amplitudes of calcium transients became larger at later time points. Consistent with CSD nature of these events, we reproducibly triggered comparable calcium transients with microinjections of potassium chloride (KCl) into adjacent cortical areas. Furthermore, lipopolysaccharide-induced peripheral inflammation, mimicking sterile inflammation during ischemic stroke, produced significantly greater microglial calcium transients during CSD. Finally, in vivo pharmacological analysis with CRAC (calcium release-activated channel) inhibitor CM-EX-137 demonstrated that CSD-associated microglial calcium transients after KCl microinjections are mediated at least in part by the CRAC mechanism.

conclusionsOur findings demonstrate that microglia participate in ischemic brain injury via previously undetected mechanisms, which may provide new avenues for therapeutic interventions.

Indexed as

Calcium SignalingMicrogliaAcute DiseaseAnimalsCalcium Channel BlockersEncephalitisImage Processing, Computer-AssistedInfarction, Middle Cerebral ArteryIschemic StrokeLipopolysaccharidesMiceMicroscopy, Fluorescence, MultiphotonMyeloid CellsPotassium ChlorideSomatosensory CortexCalcium Channel BlockersLipopolysaccharidesPotassium Chloridebraincalciumlipopolysaccharidemicrogliamicroinjection

Identifiers

PMID33161850
PMCPMC7770090
OpenAlexW3104724516

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.