Evidence map›Paper›PMID 41299539›Full record

ArticleJournal of neuroinflammation2025

NAD

Mica Cabrera, Brent Eastman, Hannah Ennerfelt, Abrar I Alsaadi, Ludmila Alexandrova, Yeonglong Albert Ay, Jolie Huang, Qian Wang, Eran Blacher, Melanie R McReynolds and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neuroinflammation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. Review
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

12 authors.

Mica Cabrera *Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Brent Eastman *Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Hannah EnnerfeltDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Abrar I AlsaadiDepartment of Biochemistry and Molecular Biology, Huck Institutes of the Life Sciences, Pennsylvania State University University Park, PA, USA.
Ludmila AlexandrovaMass Spectrometry Center, Stanford University, Stanford, CA, USA.
Yeonglong Albert AyDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Jolie HuangDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Qian WangDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Eran BlacherDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Melanie R McReynoldsDepartment of Biochemistry and Molecular Biology, Huck Institutes of the Life Sciences, Pennsylvania State University University Park, PA, USA.
Katrin I AndreassonDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Chinyere Agbaegbu IwekaDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA. cxi60@case.edu.

Funding

Research Training in Physiological Adaptations to StressT32GM108563 · NIGMS · PENNSYLVANIA STATE UNIVERSITY, THE · PI CANTORNA, MARGHERITA T, KORZICK, DONNA HOPE · 2014 to 2023
$2.2M
Modulating the post-stroke inflammatory response to improve outcome in models of cerebral ischemiaR01NS100180 · NINDS · STANFORD UNIVERSITY · PI ANDREASSON, KATRIN I. · 2018 to 2021
$1.8M
Xevo TQ-XS Triple Quadrupole Mass Spectrometer SystemS10OD026962 · OD · STANFORD UNIVERSITY · PI CHIEN, ALLIS SOE-LANG · 2019 to 2019
$527k
Nikon A1Rsi resonant spectral confocal microscopeS10OD010580 · OD · STANFORD UNIVERSITY · PI FULLER, MARGARET T · 2013 to 2013
$377k
AHA 19PABH1345800Burroughs Wellcome Postdoctoral Diversity Enrichment Program G-1022372Howard Hughes Medical Institute Hanna H. Gray Fellows Program GT15655NIGMS NIH HHS T32 GM108563NIH HHS RO1NS100180NIH HHS S10 OD010580NIH HHS S10 OD026962NIH HHS T32GM108563NINDS NIH HHS R01 NS100180The Burroughs Welcome Fund PDEP Transition to Faculty 1022604
6 · The paper itself

Abstract

backgroundAging exacerbates post-stroke inflammation, contributing to worse neurological outcomes. However, the mechanisms underlying this age-dependent immune dysregulation remain unclear. Because immune cell metabolism critically shapes inflammatory responses, we investigated whether the metabolic state of circulating monocytes, key immune cells that traffic to the ischemic brain, is altered by age after stroke. We further examined whether enhancing cellular NAD+ availability with nicotinamide riboside (NR) could mitigate age-associated neuroinflammatory responses and improve stroke outcome.

methodsIschemic stroke was induced in young and aged mice using the distal middle cerebral artery occlusion model. We assessed monocyte metabolic profiles via untargeted metabolomics, mitochondrial function assays, multi-analyte cytokine/chemokine profiling, and flow cytometry. Given the contribution of monocyte-derived intestinal macrophages to gut barrier disruption after stroke, we evaluated gut barrier integrity, immune cell composition, and systemic inflammation. Stroke outcomes were also determined by infarct size, motor function, and brain inflammatory status.

resultsOur findings show that the availability of the essential energy co-factor, NAD+, is a key age-dependent factor that regulates monocyte and intestinal macrophage immune responses after stroke. Aged monocytes showed decreased NAD+ levels and increased inflammatory responses compared to young monocytes. Pretreatment with NR elevated cellular NAD+ levels in aged monocytes, normalized intestinal macrophage numbers and activation states, preserved gut barrier integrity, reduced systemic and brain inflammation, and improved stroke outcomes in aged mice.

conclusionThese findings highlight the importance of NAD+ in mitigating the post-stroke response in aging and the potential of NAD+ supplementation as a preventive strategy for patients at risk for cerebrovascular disease.

Indexed as

AgingInflammationMonocytesNADNiacinamidePyridinium CompoundsStrokeAnimalsMaleMiceMice, Inbred C57BLNADNiacinamidenicotinamide-beta-ribosidePyridinium CompoundsAgingGutInflammationMetabolismMonocytesNAD+Nicotinamide ribosideQuinolinic acidStroke

Identifiers

PMID41299539
PMCPMC12781254

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.