Evidence map›Paper›PMID 33451354›Full record

ArticleBiology of sex differences2021

Sex differences in stroke outcome correspond to rapid and severe changes in gut permeability in adult Sprague-Dawley rats.

Yumna El-Hakim, Kathiresh Kumar Mani, Amir Eldouh, Sivani Pandey, Maria T Grimaldo, Alan Dabney, Rachel Pilla, Farida Sohrabji

Open access · goldAbstract read
In one paragraph

Article in Biology of sex differences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 pooled it
3.7field-weighted citation impact, top 6% 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

37 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.

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  20. Neural regeneration research · 2023
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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

8 authors at 2 institutions in 1 country.

Yumna El-Hakim *Women's Health in Neuroscience Program, Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University-Health, 8447 Riverside Pkwy, Bryan, TX, 77807, USA.
Kathiresh Kumar Mani *Women's Health in Neuroscience Program, Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University-Health, 8447 Riverside Pkwy, Bryan, TX, 77807, USA.
Amir EldouhWomen's Health in Neuroscience Program, Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University-Health, 8447 Riverside Pkwy, Bryan, TX, 77807, USA.
Sivani PandeyWomen's Health in Neuroscience Program, Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University-Health, 8447 Riverside Pkwy, Bryan, TX, 77807, USA.
Maria T GrimaldoWomen's Health in Neuroscience Program, Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University-Health, 8447 Riverside Pkwy, Bryan, TX, 77807, USA.
Alan DabneyDepartment of Statistics, College of Science, College Station, USA.
Rachel PillaDepartment of Small Animal Clinical Sciences, College of Veterinary Medicine, Texas A&M University, College Station, TX, USA.
Farida SohrabjiWomen's Health in Neuroscience Program, Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University-Health, 8447 Riverside Pkwy, Bryan, TX, 77807, USA. f-sohrabji@tamu.edu.ORCID 0000-0002-6960-3411
Texas A&M Health Science Center · USTexas A&M University · US

Funding

Epigenetics of the Aging Astrocyte: Implications for StrokeR01AG042189 · NIA · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · PI Farida Sohrabji · 2011 to 2026
$3.1M
Epigenetics of the Aging Astrocyte: Implications for StrokeRF1AG042189 · NIA · TEXAS A&M UNIVERSITY · PI SOHRABJI, FARIDA · 2018 to 2018
$2.8M
Neuroprotection in the Aging Female BrainR01NS074895 · NINDS · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · PI SOHRABJI, FARIDA · 2011 to 2015
$1.7M
Neuroprotection in the aging female brainR56NS074895 · NINDS · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · PI SOHRABJI, FARIDA · 2017 to 2017
$520k
NIA NIH HHS AG042189NIA NIH HHS R01 AG042189NIA NIH HHS RF1 AG042189NINDS NIH HHS NS074895NINDS NIH HHS R01 NS074895NINDS NIH HHS R56 NS074895
6 · The paper itself

Abstract

backgroundSex differences in experimental stroke outcomes are well documented, such that adult males have a greater infarct volume, increased stroke-induced mortality, and more severe sensory-motor impairment. Based on recent evidence that the gut is an early responder to stroke, the present study tested the hypothesis that sex differences in stroke severity will be accompanied by rapid and greater permeability of the gut-blood barrier and gut dysbiosis in males as compared to females.

methodMale and female Sprague-Dawley rats (5-7 months of age) were subject to endothelin (ET)-1-induced middle cerebral artery occlusion (MCAo). Sensory-motor tests were conducted pre- and 2 days after MCAo. Gut permeability was assessed in serum samples using biomarkers of gut permeability as well as functional assays using size-graded dextrans. Histological analysis of the gut was performed with H&E staining, periodic acid-Schiff for mucus, and immunohistochemistry for the tight junction protein, ZO-1. Fecal samples obtained pre- and post-stroke were analyzed for bacterial taxa and short-chain fatty acids (SCFAs).

resultsAfter stroke, males displayed greater mortality, worse sensory-motor deficit, and higher serum levels of proinflammatory cytokines IL-17A, MCP-1, and IL-5 as compared to females. MCAo-induced gut permeability was rapid and severe in males as indicated by dextran extravasation from the gut to the blood in the hyperacute (< 2 h) and early acute (2 days) phase of stroke. This was accompanied by dysmorphology of the gut villi and dysregulation of the tight junction protein ZO-1 in the acute phase. Fecal 16s sequencing showed no differences in bacterial diversity in the acute phase of stroke. Predictive modeling indicated that markers of gut permeability were associated with acute sensory-motor impairment and infarct volume.

conclusionsThese data show that extensive leakiness of the gut barrier is associated with severe post-stroke disability and suggest that reinforcing this barrier may improve stroke outcomes.

Indexed as

StrokeAnimalsBiomarkersBrain IschemiaFemaleInfarctionMalePermeabilityRatsRats, Sprague-DawleySex CharacteristicsBiomarkersDextransGut dysbiosisGut permeabilityInflammationIschemiaSex difference

Identifiers

PMID33451354
PMCPMC7811247
OpenAlexW3124911239

What OpenQuestion holds

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LicenceCC BY
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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.