Evidence map›Paper›PMID 22388811›Full record

ArticleNature2012

Treatment of stroke with a PSD-95 inhibitor in the gyrencephalic primate brain.

Douglas J Cook, Lucy Teves, Michael Tymianski

Registry-linked trialAbstract read
PubMed Publisher
In one paragraph

Article in Nature, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02930018 (A Multicentre, Randomized, Double-blinded, Placebo-controlled, Parallel Group, Single-dose Design to Determine the Efficacy and Safety of Intravenous NA-1 in Subjects With Acute Ischemic Stroke Undergoing Endovascular Thrombectomy), which is not on this map. Cited by 214 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
214citing papers in PubMed, 2 pooled it
28.4field-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.

NCT02930018 phase3completednot on this mapstarted 2017, after this paper: background citation

A Multicentre, Randomized, Double-blinded, Placebo-controlled, Parallel Group, Single-dose Design to Determine the Efficacy and Safety of Intravenous NA-1 in Subjects With Acute Ischemic Stroke Undergoing Endovascular Thrombectomy

TypeinterventionalSponsorNoNO Inc.Ran2017 to 2019Enrolled1,105ConditionsStroke, AcuteArmsNerinetide (NA-1), 2.6 mg/kg, Placebo
3 · Its place in the literature

Who cites it

214 citing papers in PubMed, 2 syntheses or guidelines pooled it, 434 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Health economic impact of Nerinetide in addition to mechanical thrombectomy without concurrent alteplase.Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences · 2026
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  9. Clinical Implications of Stroke Progressor Phenotypes defined based on ASPECTS decay and perfusion estimated infarct growth rate: insights from a large national thrombectomy registry.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
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154 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Douglas J CookToronto Western Hospital Research Institute, Toronto, Ontario, M5T 2S8, Canada.
Lucy Teves
Michael Tymianski
Toronto Western Hospital · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

All attempts at treating strokes by pharmacologically reducing the human brain's vulnerability to ischaemia have failed, leaving stroke as a leading cause of death, disability and massive socioeconomic loss worldwide. Over decades, research has failed to translate over 1,000 experimental treatments from discovery in cells and rodents to use in humans, a scientific crisis that gave rise to the prevailing belief that pharmacological neuroprotection is not feasible or practicable in higher-order brains. To provide a strategy for advancing stroke therapy, we used higher-order gyrencephalic non-human primates, which bear genetic, anatomical and behavioural similarities to humans and tested neuroprotection by PSD-95 inhibitors--promising compounds that uncouple postsynaptic density protein PSD-95 from neurotoxic signalling pathways. Here we show that stroke damage can be prevented in non-human primates in which a PSD-95 inhibitor is administered after stroke onset in clinically relevant situations. This treatment reduced infarct volumes as gauged by magnetic resonance imaging and histology, preserved the capacity of ischaemic cells to maintain gene transcription in genome-wide screens of ischaemic brain tissue, and significantly preserved neurological function in neurobehavioural assays. The degree of tissue neuroprotection by magnetic resonance imaging corresponded strongly to the preservation of neurological function, supporting the intuitive but unproven dictum that integrity of brain tissue can reflect functional outcome. Our findings establish that tissue neuroprotection and improved functional outcome after stroke is unequivocally achievable in gyrencephalic non-human primates treated with PSD-95 inhibitors. Efforts must ensue to translate these findings to humans.

Indexed as

Macaca fascicularisAnimalsBrainDisks Large Homolog 4 ProteinHumansInfarction, Middle Cerebral ArteryIntracellular Signaling Peptides and ProteinsMagnetic Resonance ImagingMaleMembrane ProteinsPeptidesStrokeTime FactorsTreatment OutcomeDisks Large Homolog 4 ProteinDLG4 protein, humanIntracellular Signaling Peptides and ProteinsMembrane ProteinsPeptidesTat-NR2B9c

Identifiers

PMID22388811
OpenAlexW2049687017

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.