Evidence map›Paper›PMID 34445252›Full record

ArticleInternational journal of molecular sciences2021

Modeling Neuroimmune Interactions in Human Subjects and Animal Models to Predict Subtype-Specific Multidrug Treatments for Gulf War Illness.

Francisco J Carrera Arias, Kristina Aenlle, Maria Abreu, Mary A Holschbach, Lindsay T Michalovicz, Kimberly A Kelly, Nancy Klimas, James P O'Callaghan, Travis J A Craddock

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.9field-weighted citation impact, top 16% 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

8 citing papers in PubMed, 19 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
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 2 institutions in 1 country.

Francisco J Carrera AriasInstitute for Neuro-Immune Medicine, Nova Southeastern University, Fort Lauderdale, FL 33314, USA.
Kristina AenlleInstitute for Neuro-Immune Medicine, Nova Southeastern University, Fort Lauderdale, FL 33314, USA.ORCID 0000-0002-9388-3652
Maria AbreuInstitute for Neuro-Immune Medicine, Nova Southeastern University, Fort Lauderdale, FL 33314, USA.
Mary A HolschbachDepartment of Psychology & Neuroscience, College of Psychology, Nova Southeastern University, Fort Lauderdale, FL 33314, USA.
Lindsay T MichaloviczHealth Effects Laboratory Division, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA.
Kimberly A KellyHealth Effects Laboratory Division, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA.ORCID 0000-0002-1146-3137
Nancy KlimasInstitute for Neuro-Immune Medicine, Nova Southeastern University, Fort Lauderdale, FL 33314, USA.ORCID 0000-0003-1459-3268
James P O'CallaghanHealth Effects Laboratory Division, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA.
Travis J A CraddockInstitute for Neuro-Immune Medicine, Nova Southeastern University, Fort Lauderdale, FL 33314, USA.ORCID 0000-0001-7244-6317
Nova Southeastern University · USCenters for Disease Control and Prevention · US

Funding

Congressionally Directed Medical Research Programs W81XWH-13-2-0085Congressionally Directed Medical Research Programs W81XWH-16-1-0552Congressionally Directed Medical Research Programs W81XWH-16-1-0632NIOSH CDC HHS Intramural funds
6 · The paper itself

Abstract

Gulf War Illness (GWI) is a persistent chronic neuroinflammatory illness exacerbated by external stressors and characterized by fatigue, musculoskeletal pain, cognitive, and neurological problems linked to underlying immunological dysfunction for which there is no known treatment. As the immune system and the brain communicate through several signaling pathways, including the hypothalamic-pituitary-adrenal (HPA) axis, it underlies many of the behavioral and physiological responses to stressors via blood-borne mediators, such as cytokines, chemokines, and hormones. Signaling by these molecules is mediated by the semipermeable blood-brain barrier (BBB) made up of a monocellular layer forming an integral part of the neuroimmune axis. BBB permeability can be altered and even diminished by both external factors (e.g., chemical agents) and internal conditions (e.g., acute or chronic stress, or cross-signaling from the hypothalamic-pituitary-gonadal (HPG) axis). Such a complex network of regulatory interactions that possess feed-forward and feedback connections can have multiple response dynamics that may include several stable homeostatic states beyond normal health. Here we compare immune and hormone measures in the blood of human clinical samples and mouse models of Gulf War Illness (GWI) subtyped by exposure to traumatic stress for subtyping this complex illness. We do this via constructing a detailed logic model of HPA-HPG-Immune regulatory behavior that also considers signaling pathways across the BBB to neuronal-glial interactions within the brain. We apply conditional interactions to model the effects of changes in BBB permeability. Several stable states are identified in the system beyond typical health. Following alignment of the human and mouse blood profiles in the context of the model, mouse brain sample measures were used to infer the neuroinflammatory state in human GWI and perform treatment simulations using a genetic algorithm to optimize the Monte Carlo simulations of the putative treatment strategies aimed at returning the ill system back to health. We identify several ideal multi-intervention strategies and potential drug candidates that may be used to treat chronic neuroinflammation in GWI.

Indexed as

Models, ImmunologicalModels, NeurologicalNeuroimmunomodulationPersian Gulf SyndromeSignal TransductionAdultAnimalsBlood-Brain BarrierDisease Models, AnimalHumansMaleMiceMiddle Agedblood–brain barriergulf war illnesshomeostatic regulationlogical modelingmultidrug treatmentsneuroinflammationpost-traumatic stress disorderregulatory biologyrepurposingtreatment course prediction

Identifiers

PMID34445252
PMCPMC8395153
OpenAlexW3191866206

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.