Evidence map›Paper›PMID 28830843›Full record

ArticleNeurobiology of disease2017

Inhibition of tPA-induced hemorrhagic transformation involves adenosine A2b receptor activation after cerebral ischemia.

Qiang Li, Xiaoning Han, Xi Lan, Xiaohua Hong, Qian Li, Yufeng Gao, Tianqi Luo, Qingwu Yang, Raymond C Koehler, Yu Zhai and 2 more

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

Article in Neurobiology of disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 1 pooled it
5.5field-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

48 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Review
  6. MRS3997, a dual adenosine ANeuropharmacology · 2025
    Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. An enriched environment improves long-term functional outcomes in mice after intracerebral hemorrhage by mechanisms that involve the Nrf2/BDNF/glutaminase pathway.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023
    Article
  12. Article
  13. Article
  14. Review
  15. Selective block of adenosine ABritish journal of pharmacology · 2022
    Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. Article
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

12 authors at 3 institutions in 2 countries.

Qiang LiDepartment of Neurology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Xiaoning HanDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Xi LanDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Xiaohua HongDivision of MR Research, Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Qian LiDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Yufeng GaoDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Tianqi LuoDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Qingwu YangDepartment of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
Raymond C KoehlerDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Yu ZhaiDepartment of Neurology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: zhaiy1123@sh9hospital.org.
Jinyuan ZhouDivision of MR Research, Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: jzhou@mri.jhu.edu.
Jian WangDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA; Department of Anatomy, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China. Electronic address: jwang79@jhmi.edu.
Johns Hopkins University · USArmy Medical University · CNShanghai Jiao Tong University · CN

Funding

Cell-Free O2 Carriers: Cerebrovascular Control &StrokeR01NS038684 · NINDS · JOHNS HOPKINS UNIVERSITY · PI KOEHLER, RAYMOND CHARLES · 2000 to 2014
$5.6M
Amide Proton Transfer (APT) MRI of Brain Tumors at 3T and 7TR01EB009731 · NIBIB · JOHNS HOPKINS UNIVERSITY · PI ZHOU, JINYUAN · 2009 to 2016
$2.9M
Neuroprotective effect of flavanol (-) epicatechin after intracerebral hemorrhageR01AT007317 · NCCIH · JOHNS HOPKINS UNIVERSITY · PI WANG, JIAN · 2012 to 2016
$2.0M
PGE2 EP1 and EP3 receptors as therapeutic targets in intracerebral hemorrhageR01NS078026 · NINDS · JOHNS HOPKINS UNIVERSITY · PI WANG, JIAN · 2012 to 2016
$1.8M
US-China Collaborative Research on Stroke ImagingR01NS083435 · NINDS · JOHNS HOPKINS UNIVERSITY · PI ZHOU, JINYUAN · 2013 to 2015
$588k
Role of PGE2 receptors in the aging brain after intracerebral hemorrhageK01AG031926 · NIA · JOHNS HOPKINS UNIVERSITY · PI WANG, JIAN · 2008 to 2012
$536k
Microglia/macrophage polarization after intracerebral hemorrhageR56NS096549 · NINDS · JOHNS HOPKINS UNIVERSITY · PI WANG, JIAN · 2017 to 2017
$488k
NCCIH NIH HHS R01 AT007317NIA NIH HHS K01 AG031926NIBIB NIH HHS R01 EB009731NINDS NIH HHS R01 NS038684NINDS NIH HHS R01 NS078026NINDS NIH HHS R01 NS083435NINDS NIH HHS R56 NS096549
6 · The paper itself

Abstract

Tissue plasminogen activator (tPA) is administered after ischemic stroke to dissolve intravascular clots, but its use can lead to hemorrhagic transformation (HT). Therapeutic strategies to reduce hemorrhagic complications of tPA might be of benefit for stroke patients. Adenosine A2b receptor (A2bR) plays pivotal roles in regulating vascular protection in peripheral organs. This study explored whether A2bR agonist BAY 60-6583 reduces hemorrhage risk after tPA usage. Using a rat transient middle cerebral artery occlusion model, we showed that mRNA and protein expression of A2bR increased to a greater extent after ischemia-reperfusion than did expression of the other three adenosine receptors (A1, A2a, and A3). tPA administration reduced A2bR expression in ischemic brain microvessels. Post-treatment with BAY 60-6583 (1mg/kg) at the start of reperfusion reduced lesion volume in the absence or presence of tPA (10mg/kg) and attenuated brain swelling, blood-brain barrier disruption, and tPA-exacerbated HT at 24h. Additionally, BAY 60-6583 mitigated sensorimotor deficits in the presence of tPA. BAY 60-6583 inhibited tPA-enhanced matrix metalloprotease-9 activation, probably through elevation of tissue inhibitor of matrix metalloproteinases-1 expression, and thereby reduced degradation of tight junction proteins. These effects would likely protect cerebrovascular integrity. A2bR agonists as an adjuvant to tPA could be a promising strategy for decreasing the risk of HT during treatment for ischemic stroke.

Indexed as

Adenosine A2 Receptor AgonistsAminopyridinesAnimalsBlood-Brain BarrierBrain IschemiaCerebral HemorrhageDisease Models, AnimalFibrinolytic AgentsMaleMatrix Metalloproteinase 9MicrovesselsNeuroprotective AgentsRandom AllocationRats, Sprague-DawleyReceptor, Adenosine A2BStrokeAdenosine A2 Receptor AgonistsAminopyridinesBAY 60-6583Fibrinolytic AgentsMatrix Metalloproteinase 9Mmp9 protein, ratNeuroprotective AgentsReceptor, Adenosine A2BTIMP1 protein, ratTissue Inhibitor of Metalloproteinase-1Tissue Plasminogen ActivatorAdenosine receptorCerebral ischemiaHemorrhagic transformationtPA

Identifiers

PMID28830843
PMCPMC5675803
OpenAlexW2746230988

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.