Evidence map›Paper›PMID 29476448›Full record

ArticleTranslational stroke research2018

Ras-Related C3 Botulinum Toxin Substrate 1 Promotes Axonal Regeneration after Stroke in Mice.

Lin Liu, Hui Yuan, Yanhua Yi, Edward C Koellhoffer, Yashasvee Munshi, Fan Bu, Yi Zhang, Zhenggang Zhang, Louise D McCullough, Jun Li

Abstract read
In one paragraph

Article in Translational stroke research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.4field-weighted citation impact, top 21% 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

20 citing papers in PubMed, 24 citations in OpenAlex.

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  18. Microglial IRF5-IRF4 regulatory axis regulates neuroinflammation after cerebral ischemia and impacts stroke outcomes.Proceedings of the National Academy of Sciences of the United States of America · 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

10 authors at 2 institutions in 1 country.

Lin LiuDepartment of Neurology, University of Texas Health Science Center, Houston, TX, USA.
Hui YuanDepartment of Neurology, University of Texas Health Science Center, Houston, TX, USA.
Yanhua YiDepartment of Neurology, University of Texas Health Science Center, Houston, TX, USA.
Edward C KoellhofferDepartment of Neurology, University of Texas Health Science Center, Houston, TX, USA.
Yashasvee MunshiDepartment of Neurology, University of Texas Health Science Center, Houston, TX, USA.
Fan BuDepartment of Neurology, University of Texas Health Science Center, Houston, TX, USA.
Yi ZhangDepartment of Neurology, Henry Ford Hospital, Detroit, MI, USA.
Zhenggang ZhangDepartment of Neurology, Henry Ford Hospital, Detroit, MI, USA.
Louise D McCulloughDepartment of Neurology, University of Texas Health Science Center, Houston, TX, USA.
Jun LiDepartment of Neurology, University of Texas Health Science Center, Houston, TX, USA. jun.li.3@uth.tmc.edu.
The University of Texas Health Science Center at Houston · USHenry Ford Hospital · US

Funding

Neuronal and Astrocytic Interaction in Recovery after StrokeR01NS099628 · NINDS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI LI, JUN · 2016 to 2020
$1.7M
The Role of CaMK Cascade in StrokeR01NS078446 · NINDS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI LI, JUN · 2012 to 2016
$1.7M
NINDS NIH HHS R01 NS078446NINDS NIH HHS R01 NS099628
6 · The paper itself

Abstract

Neurite plasticity is a critical aspect of brain functional recovery after stroke. Emerging data suggest that Ras-related C3 botulinum toxin substrate 1 (Rac1) plays a central role in axonal regeneration in the injured brain, specifically by stimulating neuronal intrinsic growth and counteracting the growth inhibitory signaling that leads to growth cone collapse. Therefore, we investigated the functional role of Rac1 in axonal regeneration after stroke.Delayed treatment with a specific Rac1 inhibitor, NSC 23766, worsened functional recovery, which was assessed by the pellet reaching test from day 14 to day 28 after stroke. It additionally reduced axonal density in the peri-infarct zone, assessed 28 days after stroke, with no effect on brain cavity size or on the number of newly formed cells. Accordingly, Rac1 overexpression using lentivirus promoted axonal regeneration and functional recovery after stroke from day 14 to day 28. Rac1 inhibition led to inactivation of pro-regenerative molecules, including mitogen-activated protein kinase kinase (p-MEK)1/2, LIM domain kinase (LIMK)1, and extracellular signal-regulated kinase (p-ERK)1/2 at 14 days after stroke. Inhibition of Rac1 reduced axonal length and number in cultured primary mouse cortical neurons using microfluidic chambers after oxygen-glucose deprivation (OGD) without affecting cell viability. In contrast, inhibition of Rac1 increased levels of glial fibrillary acidic protein, an extrinsic inhibitory signal for axonal growth, after stroke in vivo and in primary astrocytes after OGD.In conclusion, Rac1 signaling enhances axonal regeneration and improve post-stroke functional recovery in experimental models of stroke.

Indexed as

AminoquinolinesAnimalsAxonsCell HypoxiaCells, CulturedDisease Models, AnimalGene Expression RegulationGenetic VectorsGlial Fibrillary Acidic ProteinGlucoseInfarction, Middle Cerebral ArteryLim KinasesMaleMAP Kinase Kinase 1MiceMice, Inbred C57BLAminoquinolinesGlial Fibrillary Acidic ProteinGlucoseLimk1 protein, mouseLim KinasesMAP Kinase Kinase 1Mitogen-Activated Protein Kinase 3NSC 23766Pyrimidinesrac1 GTP-Binding ProteinAxonsRac1Stroke

Identifiers

PMID29476448
PMCPMC6598679
OpenAlexW2793555349

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.