Evidence map›Paper›PMID 33349013›Full record

ArticleStroke2021

Enhanced Mesenchymal Stromal Cells or Erythropoietin Provide Long-Term Functional Benefit After Neonatal Stroke.

Amara Larpthaveesarp, Praneeti Pathipati, Samuel Ostrin, Anthony Rajah, Donna Ferriero, Fernando F Gonzalez

Open access · greenAbstract read
In one paragraph

Article in Stroke, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
7.2field-weighted citation impact, top 3% 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

22 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.

  1. Pooled it
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  17. Childhood stroke.Nature reviews. Disease primers · 2022
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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

6 authors at 2 institutions in 2 countries.

Amara LarpthaveesarpDepartment of Pediatrics (A.L., P.P., S.O., A.R., D.F., F.F.G.), University of California, San Francisco.
Praneeti PathipatiDepartment of Pediatrics (A.L., P.P., S.O., A.R., D.F., F.F.G.), University of California, San Francisco.
Samuel OstrinDepartment of Pediatrics (A.L., P.P., S.O., A.R., D.F., F.F.G.), University of California, San Francisco.
Anthony RajahDepartment of Pediatrics (A.L., P.P., S.O., A.R., D.F., F.F.G.), University of California, San Francisco.
Donna FerrieroDepartment of Neurology (D.F.), University of California, San Francisco.
Fernando F GonzalezDepartment of Pediatrics (A.L., P.P., S.O., A.R., D.F., F.F.G.), University of California, San Francisco.
University of California, San Francisco · USFPT University · VN

Funding

High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) CCCU01NS092764 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JUUL, SANDRA E, WU, YVONNE W · 2016 to 2020
$12.7M
Precision Therapy for Neonatal Brain InjuryR35NS097299 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIERO, DONNA M. · 2017 to 2024
$6.3M
Enhanced cellular therapy for neonatal strokeR01NS107039 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Fernando Francisco Gonzalez · 2018 to 2026
$3.8M
NINDS NIH HHS R01 NS107039NINDS NIH HHS R35 NS097299NINDS NIH HHS U01 NS092764
6 · The paper itself

Abstract

background and purposePerinatal stroke is a common cause of life-long neurobehavioral compromise. Mesenchymal stromal cells (MSCs) and EPO (erythropoietin) have each demonstrated short-term benefit with delayed administration after stroke, and combination therapy may provide the most benefit. The purpose of this study is to determine the long-term histological and functional efficacy of enhanced, intranasal stem cell therapy (MSC preexposed to EPO) compared with standard MSC or multidose systemic EPO.

methodsTransient middle cerebral artery occlusion or sham surgery was performed in postnatal day (P) 10 Sprague-Dawley rats, who were treated with single-dose intranasal MSC, MSC preexposed to EPO (MSC/EPO), multidose systemic EPO (EPO3; 1000 u/kg per dose×3 every 72 hours), or cell-conditioned media on P13 (day 3 [P13-P19] for EPO), or on P17 (day 7 [P17-P23] for EPO). At 2 months of age, animals underwent novel object recognition, cylinder rearing, and open field testing to assess recognition memory, sensorimotor function, and anxiety in adulthood.

resultsMSC, MSC/EPO, and EPO3 improved brain volume when administered at 3 or 7 days after middle cerebral artery occlusion. MSC/EPO also enhanced long-term recognition memory with either day 3 or day 7 treatment, but EPO3 had the most long-term benefit, improving recognition memory and exploratory behavior and reducing anxiety.

conclusionsThese data suggest that single-dose MSC/EPO and multidose systemic EPO improve long-term neurobehavioral outcomes even when administration is delayed, although EPO was the most effective treatment overall. It is possible that EPO represents a final common pathway for improved long-term repair, although the specific mechanisms remain to be determined.

Indexed as

Administration, IntranasalAnimalsAnimals, NewbornAnxietyBehavior, AnimalBrainCulture Media, ConditionedEpoetin AlfaFemaleInfarction, Middle Cerebral ArteryMemoryMesenchymal Stem Cell TransplantationMotor ActivityPregnancyPsychomotor PerformanceRatsCulture Media, ConditionedEpoetin Alfaanxietyerythropoietininfarction, middle cerebral arterymesenchymal stem celltreatment outcome

Identifiers

PMID33349013
PMCPMC7770074
OpenAlexW3116350437

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.