Evidence mapPaperPMID 35098999Full record

ArticleDisease models & mechanisms2022

Zebrafish drug screening identifies candidate therapies for neuroprotection after spontaneous intracerebral haemorrhage.

Siobhan Crilly, Adrian Parry-Jones, Xia Wang, Julian N Selley, James Cook, Victor S Tapia, Craig S Anderson, Stuart M Allan, Paul R Kasher

Open access · goldAbstract read
In one paragraph

Article in Disease models & mechanisms, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.7field-weighted citation impact, top 15% 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

6 citing papers in PubMed, 14 citations in OpenAlex.

  1. Trial
  2. Review
  3. Article
  4. Review
  5. Review
  6. Review
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 3 institutions in 2 countries.

Siobhan CrillyDivision of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Oxford Road, Manchester M13 9PT, UK.ORCID 0000-0003-1046-9884
Adrian Parry-JonesGeoffrey Jefferson Brain Research Centre, The Manchester Academic Health Science Centre, Northern Care Alliance and The University of Manchester, Manchester M6 8HD, UK.
Xia WangThe George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia.
Julian N SelleyThe Biological Mass Spectrometry Core Research Facility, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, UK.
James CookDivision of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Oxford Road, Manchester M13 9PT, UK.
Victor S TapiaDivision of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Oxford Road, Manchester M13 9PT, UK.
Craig S AndersonThe George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia.
Stuart M AllanDivision of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Oxford Road, Manchester M13 9PT, UK.
Paul R KasherDivision of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Oxford Road, Manchester M13 9PT, UK.ORCID 0000-0002-9213-502X
Manchester Academic Health Science Centre · GBThe George Institute for Global Health · GBUniversity of Manchester · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Despite the global health burden, treatment of spontaneous intracerebral haemorrhage (ICH) is largely supportive, and translation of specific medical therapies has not been successful. Zebrafish larvae offer a unique platform for drug screening to rapidly identify neuroprotective compounds following ICH. We applied the Spectrum Collection library compounds to zebrafish larvae acutely after ICH to screen for decreased brain cell death and identified 150 successful drugs. Candidates were then evaluated for possible indications with other cardiovascular diseases. Six compounds were identified, including two angiotensin-converting enzyme inhibitors (ACE-Is). Ramipril and quinapril were further assessed to confirm a significant 55% reduction in brain cell death. Proteomic analysis revealed potential mechanisms of neuroprotection. Using the INTERACT2 clinical trial dataset, we demonstrated a significant reduction in the adjusted odds of an unfavourable shift in the modified Rankin scale at 90 days for patients receiving an ACE-I after ICH (versus no ACE-I; odds ratio, 0.80; 95% confidence interval, 0.68-0.95; P=0.009). The zebrafish larval model of spontaneous ICH can be used as a reliable drug screening platform and has identified therapeutics that may offer neuroprotection. This article has an associated First Person interview with the first author of the paper.

Indexed as

NeuroprotectionZebrafishAnimalsCerebral HemorrhageDrug Evaluation, PreclinicalHumansLarvaProteomicsACE inhibitorsDrug screenIntracerebral haemorrhageStrokeZebrafish

Identifiers

PMID35098999
PMCPMC8990924
OpenAlexW4210706683

What Socratic holds

Textmetadata
LicenceCC BY
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.