Evidence map›Paper›PMID 38299355›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2024

Neutrophils and Neutrophil Extracellular Traps Cause Vascular Occlusion and Delayed Cerebral Ischemia After Subarachnoid Hemorrhage in Mice.

Hussein A Zeineddine, Sung-Ha Hong, Pedram Peesh, Ari Dienel, Kiara Torres, Peeyush Thankamani Pandit, Kanako Matsumura, Shuning Huang, Wen Li, Anjali Chauhan and 6 more

Open access · greenAbstract read
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
11.8field-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

36 citing papers in PubMed, 32 citations in OpenAlex.

  1. Haemorrhage, hypercoagulability and ischaemia: Evolution of brain injury after aneurysmal subarachnoid haemorrhage.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
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  6. Microthrombi and hypercoagulability's contribution to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
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  15. The role of neutrophils in vasospasm and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: Is it time for a SAH clinical trial targeting neutrophils?Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2025
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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

16 authors at 2 institutions in 1 country.

Hussein A Zeineddine *The Vivian L. Smith Department of Neurosurgery, McGovern Medical School (H.A.Z., S.-H.H., A.D., K.T., P.T.P., K.M., J.P.H., S.L.B., D.W.M.), University of Texas Health Science Center at Houston.
Sung-Ha Hong *The Vivian L. Smith Department of Neurosurgery, McGovern Medical School (H.A.Z., S.-H.H., A.D., K.T., P.T.P., K.M., J.P.H., S.L.B., D.W.M.), University of Texas Health Science Center at Houston.ORCID 0000-0002-5292-0592
Pedram PeeshDepartment of Neurology, McGovern Medical School (P.P., A.C., S.P.M., L.D.M., J.A.), University of Texas Health Science Center at Houston.
Ari DienelThe Vivian L. Smith Department of Neurosurgery, McGovern Medical School (H.A.Z., S.-H.H., A.D., K.T., P.T.P., K.M., J.P.H., S.L.B., D.W.M.), University of Texas Health Science Center at Houston.ORCID 0000-0003-4825-5005
Kiara TorresThe Vivian L. Smith Department of Neurosurgery, McGovern Medical School (H.A.Z., S.-H.H., A.D., K.T., P.T.P., K.M., J.P.H., S.L.B., D.W.M.), University of Texas Health Science Center at Houston.
Peeyush Thankamani PanditThe Vivian L. Smith Department of Neurosurgery, McGovern Medical School (H.A.Z., S.-H.H., A.D., K.T., P.T.P., K.M., J.P.H., S.L.B., D.W.M.), University of Texas Health Science Center at Houston.
Kanako MatsumuraThe Vivian L. Smith Department of Neurosurgery, McGovern Medical School (H.A.Z., S.-H.H., A.D., K.T., P.T.P., K.M., J.P.H., S.L.B., D.W.M.), University of Texas Health Science Center at Houston.ORCID 0000-0001-7690-8435
Shuning HuangDepartment of Diagnostic and Interventional Imaging, McGovern Medical School (S.H.), University of Texas Health Science Center at Houston.
Wen LiDivision of Clinical and Translational Sciences, Department of Internal Medicine (W.L.), University of Texas Health Science Center at Houston.ORCID 0000-0002-7538-5422
Anjali ChauhanDepartment of Neurology, McGovern Medical School (P.P., A.C., S.P.M., L.D.M., J.A.), University of Texas Health Science Center at Houston.
John P HaganThe Vivian L. Smith Department of Neurosurgery, McGovern Medical School (H.A.Z., S.-H.H., A.D., K.T., P.T.P., K.M., J.P.H., S.L.B., D.W.M.), University of Texas Health Science Center at Houston.
Sean P MarrelliDepartment of Neurology, McGovern Medical School (P.P., A.C., S.P.M., L.D.M., J.A.), University of Texas Health Science Center at Houston.ORCID 0000-0001-8476-4785
Louise D McCulloughDepartment of Neurology, McGovern Medical School (P.P., A.C., S.P.M., L.D.M., J.A.), University of Texas Health Science Center at Houston.ORCID 0000-0002-8050-1686
Spiros L BlackburnThe Vivian L. Smith Department of Neurosurgery, McGovern Medical School (H.A.Z., S.-H.H., A.D., K.T., P.T.P., K.M., J.P.H., S.L.B., D.W.M.), University of Texas Health Science Center at Houston.ORCID 0000-0003-2902-5079
Jaroslaw AronowskiDepartment of Neurology, McGovern Medical School (P.P., A.C., S.P.M., L.D.M., J.A.), University of Texas Health Science Center at Houston.ORCID 0000-0002-9256-7973
Devin W McBrideThe Vivian L. Smith Department of Neurosurgery, McGovern Medical School (H.A.Z., S.-H.H., A.D., K.T., P.T.P., K.M., J.P.H., S.L.B., D.W.M.), University of Texas Health Science Center at Houston.ORCID 0000-0001-8988-3353
The University of Texas Health Science Center · USThe University of Texas Health Science Center at Houston · US

Funding

Convalescent Plasma to Limit Coronavirus Associated ComplicationsUL1TR003167 · NCATS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI KARP, DANIEL D, MCPHERSON, DAVID D · 2019 to 2023
$45.3M
Role of Microthrombi and Inflammation in Delayed Deficits after SAHR01NS115887 · NINDS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI MCBRIDE, DEVIN WILLIAM · 2021 to 2025
$2.7M
Role of Haptoglobin Genotype on Neuroinflammation and Coagulation Following Aneurysmal Subarachnoid HemorrhageK23NS106054 · NINDS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI BLACKBURN, SPIROS · 2018 to 2022
$875k
Research Training for Neurosurgery and Neurology Residents & FellowsR25NS113757 · NINDS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI LHATOO, SAMDEN, TANDON, NITIN · 2020 to 2023
$356k
NCATS NIH HHS UL1 TR003167NINDS NIH HHS K23 NS106054NINDS NIH HHS R01 NS115887NINDS NIH HHS R25 NS113757
6 · The paper itself

Abstract

backgroundAfter subarachnoid hemorrhage (SAH), neutrophils are deleterious and contribute to poor outcomes. Neutrophils can produce neutrophil extracellular traps (NETs) after ischemic stroke. Our hypothesis was that, after SAH, neutrophils contribute to delayed cerebral ischemia (DCI) and worse outcomes via cerebrovascular occlusion by NETs.

methodsSAH was induced via endovascular perforation, and SAH mice were given either a neutrophil-depleting antibody, a PAD4 (peptidylarginine deiminase 4) inhibitor (to prevent NETosis), DNAse-I (to degrade NETs), or a vehicle control. Mice underwent daily neurological assessment until day 7 and then euthanized for quantification of intravascular brain NETs (iNETs). Subsets of mice were used to quantify neutrophil infiltration, NETosis potential, iNETs, cerebral perfusion, and infarction. In addition, NET markers were assessed in the blood of aneurysmal SAH patients.

resultsIn mice, SAH led to brain neutrophil infiltration within 24 hours, induced a pro-NETosis phenotype selectively in skull neutrophils, and caused a significant increase in iNETs by day 1, which persisted until at least day 7. Neutrophil depletion significantly reduced iNETs, improving cerebral perfusion, leading to less neurological deficits and less incidence of DCI (16% versus 51.9%). Similarly, PAD4 inhibition reduced iNETs, improved neurological outcome, and reduced incidence of DCI (5% versus 30%), whereas degrading NETs marginally improved outcomes. Patients with aneurysmal SAH who developed DCI had elevated markers of NETs compared with non-DCI patients.

conclusionsAfter SAH, skull-derived neutrophils are primed for NETosis, and there are persistent brain iNETs, which correlated with delayed deficits. The findings from this study suggest that, after SAH, neutrophils and NETosis are therapeutic targets, which can prevent vascular occlusion by NETs in the brain, thereby lessening the risk of DCI. Finally, NET markers may be biomarkers, which can predict which patients with aneurysmal SAH are at risk for developing DCI.

Indexed as

Brain IschemiaCerebrovascular DisordersExtracellular TrapsSubarachnoid HemorrhageAnimalsHumansMiceNeutrophilsbiomarkersbraindelayed cerebral ischemianeutrophil extracellular trapssubarachnoid hemorrhage

Identifiers

PMID38299355
PMCPMC10923061
OpenAlexW4391439126

What Socratic 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 Socratic graph.