Evidence map›Paper›PMID 26420220›Full record

ArticleStem cell research & therapy2015

Pre-differentiation of human neural stem cells into GABAergic neurons prior to transplant results in greater repopulation of the damaged brain and accelerates functional recovery after transient ischemic stroke.

Hima C S Abeysinghe, Laita Bokhari, Anita Quigley, Mahesh Choolani, Jerry Chan, Gregory J Dusting, Jeremy M Crook, Nao R Kobayashi, Carli L Roulston

Open access · goldAbstract read
In one paragraph

Article in Stem cell research & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.1field-weighted citation impact, top 14% 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

28 citing papers in PubMed, 48 citations in OpenAlex.

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  19. Recent Advances in Cell-Based Therapies for Ischemic Stroke.International journal of molecular sciences · 2020
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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

9 authors at 4 institutions in 2 countries.

Hima C S AbeysingheNeurotrauma Research Team, Department of Medicine, University of Melbourne, Level 4, Clinical Sciences Building, 29 Regent Street, Fitzroy, VIC, 3065, Australia. himaa@student.unimelb.edu.au.
Laita BokhariNeurotrauma Research Team, Department of Medicine, University of Melbourne, Level 4, Clinical Sciences Building, 29 Regent Street, Fitzroy, VIC, 3065, Australia. laita.bokhari@unimelb.edu.au.
Anita QuigleyARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, AIIM Facility, Innovation Campus, University of Wollongong, Squires Way, Fairy Meadow, NSW 2519, Australia. anita.quigley@svhm.org.au.
Mahesh ChoolaniDepartment of Obstetrics and Gynecology, National University of Singapore, Singapore, Singapore. mahesh_a_choolani@nuhs.edu.sg.
Jerry ChanDepartment of Obstetrics and Gynecology, National University of Singapore, Singapore, Singapore. jerrychan@nus.edu.sg.
Gregory J DustingCytoprotection Pharmacology Program, Centre for Eye Research, The Royal Eye and Ear Hospital Melbourne, Melbourne, VIC, Australia. g.dusting@unimelb.edu.au.
Jeremy M CrookDepartment of Surgery, University of Melbourne, Melbourne, VIC, Australia. jcrook@uow.edu.au.
Nao R KobayashiARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, AIIM Facility, Innovation Campus, University of Wollongong, Squires Way, Fairy Meadow, NSW 2519, Australia.
Carli L RoulstonNeurotrauma Research Team, Department of Medicine, University of Melbourne, Level 4, Clinical Sciences Building, 29 Regent Street, Fitzroy, VIC, 3065, Australia. carlir@unimelb.edu.au.
University of Melbourne · AUARC Centre of Excellence for Electromaterials Science · AUNational University of Singapore · SGUniversity of Wollongong · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionDespite attempts to prevent brain injury during the hyperacute phase of stroke, most sufferers end up with significant neuronal loss and functional deficits. The use of cell-based therapies to recover the injured brain offers new hope. In the current study, we employed human neural stem cells (hNSCs) isolated from subventricular zone (SVZ), and directed their differentiation into GABAergic neurons followed by transplantation to ischemic brain.

methodsPre-differentiated GABAergic neurons, undifferentiated SVZ-hNSCs or media alone were stereotaxically transplanted into the rat brain (n=7/group) 7 days after endothelin-1 induced stroke. Neurological outcome was assessed by neurological deficit scores and the cylinder test. Transplanted cell survival, cellular phenotype and maturation were assessed using immunohistochemistry and confocal microscopy.

resultsBehavioral assessments revealed accelerated improvements in motor function 7 days post-transplant in rats treated with pre-differentiated GABAergic cells in comparison to media alone and undifferentiated hNSC treated groups. Histopathology 28 days-post transplant indicated that pre-differentiated cells maintained their GABAergic neuronal phenotype, showed evidence of synaptogenesis and up-regulated expression of both GABA and calcium signaling proteins associated with neurotransmission. Rats treated with pre-differentiated cells also showed increased neurogenic activity within the SVZ at 28 days, suggesting an additional trophic role of these GABAergic cells. In contrast, undifferentiated SVZ-hNSCs predominantly differentiated into GFAP-positive astrocytes and appeared to be incorporated into the glial scar.

conclusionOur study is the first to show enhanced exogenous repopulation of a neuronal phenotype after stroke using techniques aimed at GABAergic cell induction prior to delivery that resulted in accelerated and improved functional recovery.

Indexed as

AnimalsCells, CulturedCell SurvivalCerebral CortexGABAergic NeuronsInfarction, Middle Cerebral ArteryIschemic Attack, TransientMaleMotor ActivityNeural Stem CellsNeurogenesisRats, WistarRecovery of Function

Identifiers

PMID26420220
PMCPMC4588906
OpenAlexW2172005164

What OpenQuestion 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 OpenQuestion graph.