Evidence map›Paper›PMID 26132738›Full record

ArticleCell transplantation2016

Optogenetic Stimulation of Neural Grafts Enhances Neurotransmission and Downregulates the Inflammatory Response in Experimental Stroke Model.

Marcel M Daadi, Jill Q Klausner, Bryce Bajar, Inbal Goshen, Christopher Lee-Messer, Soo Yeun Lee, Mårten C G Winge, Charu Ramakrishnan, Maisie Lo, Guohua Sun and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell transplantation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 2 pooled it
2.8field-weighted citation impact, top 10% 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

29 citing papers in PubMed, 2 syntheses or guidelines pooled it, 43 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Article
  5. Review
  6. Wrap it up: myelination of transplanted neurons for repair.Frontiers in cellular neuroscience · 2025
    Review
  7. Advanced rehabilitation in ischaemic stroke research.Stroke and vascular neurology · 2024
    Review
  8. Review
  9. Review
  10. Physical therapy exerts sub-additive and suppressive effects on intracerebral neural stem cell implantation in a rat model of stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022
    Article
  11. Review
  12. Optogenetic Control of Human Stem Cell-Derived Neurons.Methods in molecular biology (Clifton, N.J.) · 2022
    Article
  13. Review
  14. Application of Optogenetics for Muscle Cells and Stem Cells.Advances in experimental medicine and biology · 2021
    Article
  15. Article
  16. Article
  17. Activity in grafted human iPS cell-derived cortical neurons integrated in stroke-injured rat brain regulates motor behavior.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  18. Review
  19. Article
  20. 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

12 authors at 1 institution in 1 country.

Marcel M DaadiDepartment of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
Jill Q Klausner
Bryce Bajar
Inbal Goshen
Christopher Lee-Messer
Soo Yeun Lee
Mårten C G Winge
Charu Ramakrishnan
Maisie Lo
Guohua Sun
Karl Deisseroth
Gary K Steinberg
Stanford University · US

Funding

Paracrine and synaptic mechanisms underlying recovery using human stem cell theraR01NS058784 · NINDS · STANFORD UNIVERSITY · PI STEINBERG, GARY K · 2008 to 2023
$6.6M
NINDS NIH HHS R01 NS058784
6 · The paper itself

Abstract

Compelling evidence suggests that transplantation of neural stem cells (NSCs) from multiple sources ameliorates motor deficits after stroke. However, it is currently unknown to what extent the electrophysiological activity of grafted NSC progeny participates in the improvement of motor deficits and whether excitatory phenotypes of the grafted cells are beneficial or deleterious to sensorimotor performances. To address this question, we used optogenetic tools to drive the excitatory outputs of the grafted NSCs and assess the impact on local circuitry and sensorimotor performance. We genetically engineered NSCs to express the Channelrhodopsin-2 (ChR2), a light-gated cation channel that evokes neuronal depolarization and initiation of action potentials with precise temporal control to light stimulation. To test the function of these cells in a stroke model, rats were subjected to an ischemic stroke and grafted with ChR2-NSCs. The grafted NSCs identified with a human-specific nuclear marker survived in the peri-infarct tissue and coexpressed the ChR2 transgene with the neuronal markers TuJ1 and NeuN. Gene expression analysis in stimulated versus vehicle-treated animals showed a differential upregulation of transcripts involved in neurotransmission, neuronal differentiation, regeneration, axonal guidance, and synaptic plasticity. Interestingly, genes involved in the inflammatory response were significantly downregulated. Behavioral analysis demonstrated that chronic optogenetic stimulation of the ChR2-NSCs enhanced forelimb use on the stroke-affected side and motor activity in an open field test. Together these data suggest that excitatory stimulation of grafted NSCs elicits beneficial effects in experimental stroke model through cell replacement and non-cell replacement, anti-inflammatory/neurotrophic effects.

Indexed as

Down-RegulationSynaptic TransmissionAnimalsCell SeparationDisease Models, AnimalGene Expression ProfilingHuman Embryonic Stem CellsHumansInflammationMaleNeostriatumNeural Stem CellsOligonucleotide Array Sequence AnalysisOptogeneticsRats, Sprague-DawleyRhodopsinRhodopsin

Identifiers

PMID26132738
PMCPMC5823260
OpenAlexW759258118

What OpenQuestion 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 OpenQuestion graph.