Evidence map›Paper›PMID 26685158›Full record

ArticleBrain : a journal of neurology2016

Enhanced phasic GABA inhibition during the repair phase of stroke: a novel therapeutic target.

Takeshi Hiu, Zoya Farzampour, Jeanne T Paz, Eric Hou Jen Wang, Corrine Badgely, Andrew Olson, Kristina D Micheva, Gordon Wang, Robin Lemmens, Kevin V Tran and 8 more

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

Article in Brain : a journal of neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed, 3 pooled it
4.6field-weighted citation impact, top 4% 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

70 citing papers in PubMed, 3 syntheses or guidelines pooled it, 129 citations in OpenAlex.

  1. Systematic review of repetitive transcranial magnetic stimulation for post-stroke hemiplegic shoulder pain.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025
    Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Review
  6. Article
  7. Zolpidem restores sleep and decreases amyloid in a mouse model.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. TRPM2 and CaMKII Signaling Drives Excessive GABAergic Synaptic Inhibition Following Ischemia.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024
    Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article

10 more citing papers are in PubMed but not listed here.

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

18 authors at 2 institutions in 2 countries.

Takeshi Hiu1 Department of Neurosurgery, Stanford University, Stanford, CA, USA 2 Stanford Stroke Centre, Palo Alto, CA 94304, USA tbliss1@stanford.edu gsteinberg@stanford.edu.
Zoya Farzampour3 Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA tbliss1@stanford.edu gsteinberg@stanford.edu.
Jeanne T Paz3 Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA 4 Gladstone Institute of Neurological Disease and University of California, San Francisco San Francisco, CA USA.
Eric Hou Jen Wang1 Department of Neurosurgery, Stanford University, Stanford, CA, USA 2 Stanford Stroke Centre, Palo Alto, CA 94304, USA.
Corrine Badgely3 Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.
Andrew Olson1 Department of Neurosurgery, Stanford University, Stanford, CA, USA.
Kristina D Micheva5 Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA, USA.
Gordon Wang5 Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA, USA.
Robin Lemmens1 Department of Neurosurgery, Stanford University, Stanford, CA, USA 2 Stanford Stroke Centre, Palo Alto, CA 94304, USA 6 KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology; VIB - Vesalius Research Center University Hospitals Leuven, Department of Neurology, B-3000 Leuven, Belgium.
Kevin V Tran1 Department of Neurosurgery, Stanford University, Stanford, CA, USA 2 Stanford Stroke Centre, Palo Alto, CA 94304, USA.
Yasuhiro Nishiyama1 Department of Neurosurgery, Stanford University, Stanford, CA, USA 2 Stanford Stroke Centre, Palo Alto, CA 94304, USA.
Xibin Liang1 Department of Neurosurgery, Stanford University, Stanford, CA, USA 2 Stanford Stroke Centre, Palo Alto, CA 94304, USA.
Scott A Hamilton1 Department of Neurosurgery, Stanford University, Stanford, CA, USA 2 Stanford Stroke Centre, Palo Alto, CA 94304, USA.
Nancy O'Rourke5 Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA, USA.
Stephen J Smith5 Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA, USA.
John R Huguenard3 Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.
Tonya M Bliss1 Department of Neurosurgery, Stanford University, Stanford, CA, USA 2 Stanford Stroke Centre, Palo Alto, CA 94304, USA.
Gary K Steinberg1 Department of Neurosurgery, Stanford University, Stanford, CA, USA 2 Stanford Stroke Centre, Palo Alto, CA 94304, USA 3 Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA tbliss1@stanford.edu gsteinberg@stanford.edu.
Stanford University · USStanford Medicine · US

Funding

Transgenic Mouse and Biobank CoreP01CA095616 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BRENNAN, CAMERON · 2003 to 2012
$20.3M
UC Davis/NIH NeuroMab FacilityU24NS050606 · NINDS · UNIVERSITY OF CALIFORNIA DAVIS · PI TRIMMER, JAMES S · 2005 to 2014
$15.6M
Synaptomes of Mouse and ManR01NS092474 · NINDS · ALLEN INSTITUTE · PI BURNS, RANDAL, SMITH, STEPHEN J · 2014 to 2018
$8.7M
Paracrine and synaptic mechanisms underlying recovery using human stem cell theraR01NS058784 · NINDS · STANFORD UNIVERSITY · PI STEINBERG, GARY K · 2008 to 2023
$6.6M
VECTOR COREP30NS069375 · NINDS · STANFORD UNIVERSITY · PI SHAMLOO, MEHRDAD · 2011 to 2019
$6.3M
Inhibitory Controls of Thalamic NeuronsR01NS034774 · NINDS · STANFORD UNIVERSITY · PI HUGUENARD, JOHN R · 1996 to 2021
$5.5M
CELLULAR MECHANISMS IN FOCAL EPILEPTOGENESISR01NS006477 · NINDS · STANFORD UNIVERSITY · PI HUGUENARD, JOHN R · 1985 to 2013
$5.0M
The Role of Inflammation in Post-stroke EpileptogenesisR01NS096369 · NINDS · J. DAVID GLADSTONE INSTITUTES · PI PAZ, JEANNE T · 2016 to 2021
$2.3M
Astrocytic Control of GABA Inhibition in EpilepsyR01NS090911 · NINDS · STANFORD UNIVERSITY · PI HUGUENARD, JOHN R · 2014 to 2017
$1.5M
Role of Thalamus in Post-stroke epileptogenesisR00NS078118 · NINDS · J. DAVID GLADSTONE INSTITUTES · PI PAZ, JEANNE T · 2014 to 2016
$747k
Role of Thalamus in Post-stroke epileptogenesisK99NS078118 · NINDS · STANFORD UNIVERSITY · PI PAZ, JEANNE T · 2012 to 2013
$179k
NCI NIH HHS P01 CA095616NINDS NIH HHS 5R01NS006477NINDS NIH HHS 5R01NS034774NINDS NIH HHS K99NS078118-01NINDS NIH HHS P30 NS069375NINDS NIH HHS R00 NS078118NINDS NIH HHS R01 NS058784NINDS NIH HHS R01 NS090911NINDS NIH HHS R01 NS096369NINDS NIH HHS U24 NS050606
6 · The paper itself

Abstract

Ischaemic stroke is the leading cause of severe long-term disability yet lacks drug therapies that promote the repair phase of recovery. This repair phase of stroke occurs days to months after stroke onset and involves brain remapping and plasticity within the peri-infarct zone. Elucidating mechanisms that promote this plasticity is critical for the development of new therapeutics with a broad treatment window. Inhibiting tonic (extrasynaptic) GABA signalling during the repair phase was reported to enhance functional recovery in mice suggesting that GABA plays an important function in modulating brain repair. While tonic GABA appears to suppress brain repair after stroke, less is known about the role of phasic (synaptic) GABA during the repair phase. We observed an increase in postsynaptic phasic GABA signalling in mice within the peri-infarct cortex specific to layer 5; we found increased numbers of α1 receptor subunit-containing GABAergic synapses detected using array tomography, and an associated increased efficacy of spontaneous and miniature inhibitory postsynaptic currents in pyramidal neurons. Furthermore, we demonstrate that enhancing phasic GABA signalling using zolpidem, a Food and Drug Administration (FDA)-approved GABA-positive allosteric modulator, during the repair phase improved behavioural recovery. These data identify potentiation of phasic GABA signalling as a novel therapeutic strategy, indicate zolpidem's potential to improve recovery, and underscore the necessity to distinguish the role of tonic and phasic GABA signalling in stroke recovery.

Indexed as

Drug Delivery SystemsAnimalsGABA-A Receptor AgonistsMaleMiceMice, Inbred C57BLNeocortexNeural InhibitionOrgan Culture TechniquesPyridinesReceptors, GABA-ARecovery of FunctionStrokeZolpidemGABA-A Receptor AgonistsPyridinesReceptors, GABA-AZolpidembrain repairphasic GABAstrokezolpidem

Identifiers

PMID26685158
PMCPMC4805083
OpenAlexW2198818358

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.