Evidence map›Paper›PMID 32147438›Full record

ArticleExperimental neurology2020

Human neural stem cells improve early stage stroke outcome in delayed tissue plasminogen activator-treated aged stroke brains.

Austin C Boese, Auston Eckert, Milton H Hamblin, Jean-Pyo Lee

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

Article in Experimental neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

27 citing papers in PubMed, 47 citations in OpenAlex.

  1. Article
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  3. The blood-brain barrier: a help and a hindrance.Brain : a journal of neurology · 2025
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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

4 authors at 1 institution in 1 country.

Austin C BoeseDepartment of Physiology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Auston EckertDepartment of Physiology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Milton H HamblinDepartment of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Jean-Pyo LeeDepartment of Physiology, Tulane University School of Medicine, New Orleans, LA 70112, USA; Tulane Brain Institute, Tulane University, New Orleans, LA 70112, USA. Electronic address: jeanpyoL@tulane.edu.
Tulane University · US

Funding

Combination treatment of ischemic stroke with perlecan DV and neural stem cellsR01NS110370 · NINDS · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI BIX, GREGORY JAYE, LEE, JEAN-PYO · 2019 to 2023
$2.4M
NINDS NIH HHS R01 NS110370
6 · The paper itself

Abstract

introductionClinically, significant stroke injury results from ischemia-reperfusion (IR), which induces a deleterious biphasic opening of the blood-brain barrier (BBB). Tissue plasminogen activator (tPA) remains the sole pharmacological agent to treat ischemic stroke. However, major limitations of tPA treatment include a narrow effective therapeutic window of 4.5 h in most patients after initial stroke onset and off-target non-thrombolytic effects (e.g., the risk of increased IR injury). We hypothesized that ameliorating BBB damage with exogenous human neural stem cells (hNSCs) would improve stroke outcome to a greater extent than treatment with delayed tPA alone in aged stroke mice.

methodsWe employed middle cerebral artery occlusion to produce focal ischemia with subsequent reperfusion (MCAO/R) in aged mice and administered tPA at a delayed time point (6 h post-stroke) via tail vein. We transplanted hNSCs intracranially in the subacute phase of stroke (24 h post-stroke). We assessed the outcomes of hNSC transplantation on pathophysiological markers of stroke 48 h post-stroke (24 h post-transplant).

resultsDelayed tPA treatment resulted in more extensive BBB damage and inflammation relative to MCAO controls. Notably, transplantation of hNSCs ameliorated delayed tPA-induced escalated stroke damage; decreased expression of proinflammatory factors (tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6), decreased the level of matrix metalloprotease-9 (MMP-9), increased the level of brain-derived neurotrophic factor (BDNF), and reduced BBB damage.

conclusionsAged stroke mice that received delayed tPA treatment in combination with hNSC transplantation exhibited reduced stroke pathophysiology in comparison to non-transplanted stroke mice with delayed tPA. This suggests that hNSC transplantation may synergize with already existing stroke therapies to benefit a larger stroke patient population.

Indexed as

AgingAnimalsBrainCells, CulturedHumansMaleMiceMice, Inbred C57BLNeural Stem CellsStem Cell TransplantationStrokeTime-to-TreatmentTissue Plasminogen ActivatorTreatment OutcomeTissue Plasminogen ActivatorBlood-brain barrierInflammationNeural stem cellsStem cell transplantationStrokeTissue plasminogen activator

Identifiers

PMID32147438
PMCPMC7609039
OpenAlexW3010084808

What OpenQuestion holds

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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.