Evidence map›Paper›PMID 34073791›Full record

ArticleBiomedicines2021

Involvement of mTOR Pathways in Recovery from Spinal Cord Injury by Modulation of Autophagy and Immune Response.

Ingrid Vargova, Lucia Machova Urdzikova, Kristyna Karova, Barbora Smejkalova, Tolga Sursal, Veronika Cimermanova, Karolina Turnovcova, Chirag D Gandhi, Meena Jhanwar-Uniyal, Pavla Jendelova

Open access · goldAbstract read
In one paragraph

Article in Biomedicines, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

10 citing papers in PubMed, 13 citations in OpenAlex.

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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 2 countries.

Ingrid VargovaInstitute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska, 1083, 142 20 Prague, Czech Republic.
Lucia Machova UrdzikovaInstitute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska, 1083, 142 20 Prague, Czech Republic.
Kristyna KarovaInstitute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska, 1083, 142 20 Prague, Czech Republic.
Barbora SmejkalovaInstitute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska, 1083, 142 20 Prague, Czech Republic.ORCID 0000-0002-4812-9458
Tolga SursalDepartment of Neurosurgery, Westchester Medical Center, New York Medical College, Valhalla, NY 10595, USA.
Veronika CimermanovaInstitute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska, 1083, 142 20 Prague, Czech Republic.
Karolina TurnovcovaInstitute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska, 1083, 142 20 Prague, Czech Republic.
Chirag D GandhiDepartment of Neurosurgery, Westchester Medical Center, New York Medical College, Valhalla, NY 10595, USA.
Meena Jhanwar-UniyalDepartment of Neurosurgery, Westchester Medical Center, New York Medical College, Valhalla, NY 10595, USA.
Pavla JendelovaInstitute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska, 1083, 142 20 Prague, Czech Republic.ORCID 0000-0002-4644-9212
Czech Academy of Sciences · CZWestchester Medical Center · US

Funding

Ministerstvo Školství, Mládeže a Tělovýchovy CZ.02.1.01/0.0./0.0/15_003/0000419Ministerstvo Školství, Mládeže a Tělovýchovy LTAUSA17120
6 · The paper itself

Abstract

Traumatic spinal cord injury (SCI) is untreatable and remains the leading cause of disability. Neuroprotection and recovery after SCI can be partially achieved by rapamycin (RAPA) treatment, an inhibitor of mTORC1, complex 1 of the mammalian target of rapamycin (mTOR) pathway. However, mechanisms regulated by the mTOR pathway are not only controlled by mTORC1, but also by a second mTOR complex (mTORC2). Second-generation inhibitor, pp242, inhibits both mTORC1 and mtORC2, which led us to explore its therapeutic potential after SCI and compare it to RAPA treatment. In a rat balloon-compression model of SCI, the effect of daily RAPA (5 mg/kg; IP) and pp242 (5 mg/kg; IP) treatment on inflammatory responses and autophagy was observed. We demonstrated inhibition of the mTOR pathway after SCI through analysis of p-S6, p-Akt, and p-4E-BP1 levels. Several proinflammatory cytokines were elevated in pp242-treated rats, while RAPA treatment led to a decrease in proinflammatory cytokines. Both RAPA and pp242 treatments caused an upregulation of LC3B and led to improved functional and structural recovery in acute SCI compared to the controls, however, a greater axonal sprouting was seen following RAPA treatment. These results suggest that dual mTOR inhibition by pp242 after SCI induces distinct mechanisms and leads to recovery somewhat inferior to that following RAPA treatment.

Indexed as

autophagydual inhibitioninflammationmTORpp242rapamycinspinal cord injury

Identifiers

PMID34073791
PMCPMC8225190
OpenAlexW3164919926

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Registered trials

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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.