Evidence map›Paper›PMID 31007531›Full record

ReviewJournal of central nervous system disease2019

Targeting the Blood-Brain Barrier to Prevent Sepsis-Associated Cognitive Impairment.

Divine C Nwafor, Allison L Brichacek, Afroz S Mohammad, Jessica Griffith, Brandon P Lucke-Wold, Stanley A Benkovic, Werner J Geldenhuys, Paul R Lockman, Candice M Brown

Open access · goldAbstract readReview
In one paragraph

Review in Journal of central nervous system disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed, 2 pooled it
11.0field-weighted citation impact, top 1% 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

73 citing papers in PubMed, 2 syntheses or guidelines pooled it, 120 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Obstacles and Trials in Treating Primary Brain Tumors.International journal of molecular sciences · 2026
    Review
  4. Observational
  5. Article
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  11. Article
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  18. Genetic differences in hippocampus of mice susceptible to sepsis-associated encephalopathy.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2024
    Article
  19. Article
  20. Review

13 more citing papers are in PubMed but not listed here.

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

9 authors at 1 institution in 1 country.

Divine C NwaforGraduate Programs in Neuroscience, Department of Neuroscience, School of Medicine, Health Sciences Center, West Virginia University, Morgantown, WV, USA.
Allison L BrichacekImmunology and Microbial Pathogenesis, School of Medicine, Health Sciences Center, West Virginia University, Morgantown, WV, USA.
Afroz S MohammadDepartment of Pharmaceutical Sciences, School of Pharmacy, Health Sciences Center, West Virginia University, Morgantown, WV, USA.
Jessica GriffithDepartment of Pharmaceutical Sciences, School of Pharmacy, Health Sciences Center, West Virginia University, Morgantown, WV, USA.
Brandon P Lucke-WoldGraduate Programs in Neuroscience, Department of Neuroscience, School of Medicine, Health Sciences Center, West Virginia University, Morgantown, WV, USA.
Stanley A BenkovicDepartment of Neuroscience, School of Medicine, Health Sciences Center, West Virginia University, Morgantown, WV, USA.
Werner J GeldenhuysGraduate Programs in Neuroscience, Department of Neuroscience, School of Medicine, Health Sciences Center, West Virginia University, Morgantown, WV, USA.
Paul R LockmanGraduate Programs in Neuroscience, Department of Neuroscience, School of Medicine, Health Sciences Center, West Virginia University, Morgantown, WV, USA.
Candice M BrownGraduate Programs in Neuroscience, Department of Neuroscience, School of Medicine, Health Sciences Center, West Virginia University, Morgantown, WV, USA.ORCID https://orcid.org/0000-0001-5845-0221
West Virginia University · US

Funding

West Virginia IDEA-CTRU54GM104942 · NIGMS · WEST VIRGINIA UNIVERSITY · PI Sally Lynn Hodder · 2012 to 2026
$81.0M
West Virginia University Stroke COBREP20GM109098 · NIGMS · WEST VIRGINIA UNIVERSITY · PI HRUSKA, MARTIN · 2014 to 2024
$24.5M
Stroke and Alzheimers Disease Related DementiasT32AG052375 · NIA · WEST VIRGINIA UNIVERSITY · PI Paul D Chantler, BERNARD G. SCHREURS · 2017 to 2026
$3.5M
Estradiol Regulation of Brain-Microvascular Inflammatory Responses in SepsisK01NS081014 · NINDS · WEST VIRGINIA UNIVERSITY · PI BROWN, CANDICE · 2012 to 2016
$714k
NIA NIH HHS T32 AG052375NIGMS NIH HHS P20 GM109098NIGMS NIH HHS U54 GM104942NINDS NIH HHS K01 NS081014
6 · The paper itself

Abstract

Sepsis is a systemic inflammatory disease resulting from an infection. This disorder affects 750 000 people annually in the United States and has a 62% rehospitalization rate. Septic symptoms range from typical flu-like symptoms (eg, headache, fever) to a multifactorial syndrome known as sepsis-associated encephalopathy (SAE). Patients with SAE exhibit an acute altered mental status and often have higher mortality and morbidity. In addition, many sepsis survivors are also burdened with long-term cognitive impairment. The mechanisms through which sepsis initiates SAE and promotes long-term cognitive impairment in septic survivors are poorly understood. Due to its unique role as an interface between the brain and the periphery, numerous studies support a regulatory role for the blood-brain barrier (BBB) in the progression of acute and chronic brain dysfunction. In this review, we discuss the current body of literature which supports the BBB as a nexus which integrates signals from the brain and the periphery in sepsis. We highlight key insights on the mechanisms that contribute to the BBB's role in sepsis which include neuroinflammation, increased barrier permeability, immune cell infiltration, mitochondrial dysfunction, and a potential barrier role for tissue non-specific alkaline phosphatase (TNAP). Finally, we address current drug treatments (eg, antimicrobials and intravenous immunoglobulins) for sepsis and their potential outcomes on brain function. A comprehensive understanding of these mechanisms may enable clinicians to target specific aspects of BBB function as a therapeutic tool to limit long-term cognitive impairment in sepsis survivors.

Indexed as

blood-brain barrierdrug deliveryneuroinflammationSepsissepsis-associated encephalopathytissue non-specific alkaline phosphatase

Identifiers

PMID31007531
PMCPMC6456845
OpenAlexW2940220126

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.