Evidence map›Paper›PMID 41948314›Full record

ReviewFrontiers in immunology2026

The nitrate-nitrite-nitric oxide pathway of neuroinflammation and cognitive impairment in ischemic stroke.

Jinyan Liu, Qiuyue Deng, Shufei Wei, Lin Cheng, Chunxiao Shen, Ziying Liu, Yuemin Qiu, Jiahui Teng, Liangliang Wang, Xiaorong Zhang

Abstract readReview
In one paragraph

Review in Frontiers in immunology, 2026. 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

10 authors.

Jinyan Liu *Department of Pathology, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi, China.
Qiuyue Deng *Department of Pathology, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi, China.
Shufei WeiDepartment of Pathology, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi, China.
Lin ChengJiujiang Clinical Precision Medicine Research Center, Jiujiang, Jiangxi, China.
Chunxiao ShenDepartment of Pathology, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi, China.
Ziying LiuDepartment of Pathology, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi, China.
Yuemin Qiu *Department of Pathology, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi, China.
Jiahui TengDepartment of Pathology, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi, China.
Liangliang WangDepartment of Pathology, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi, China.
Xiaorong ZhangDepartment of Pathology, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Ischemic stroke is the most prevalent type of stroke worldwide and poses a serious threat to human health. Neuroinflammation following an ischemic stroke is a key factor in cognitive impairment and disease progression, yet effective interventions are lacking. The classical L-arginine-nitric oxide synthase (L-arginine-NO) pathway for nitric oxide (NO) synthesis becomes impaired under ischemic and hypoxic conditions. This review focuses on an essential alternative pathway: the nitrate-nitrite-NO pathway, which is preferentially activated under hypoxic conditions and serves as a 'backup system' for maintaining NO bioavailability. This review outlines the epidemiology and pathomechanisms of ischemic stroke and introduces the biochemical basis of the NO pathway. It emphasizes the pathway's dual role in ischemic stroke, exerting anti-inflammatory and neuroprotective effects by mediating vasodilation, improving cerebral perfusion, regulating microglial polarization, preserving blood-brain barrier integrity, and promoting synaptic plasticity. This mitigates cognitive impairment. Conversely, the review also explores the potential neurotoxic effects of excessive NO during the late reperfusion phase. Furthermore, this review discusses novel therapeutic strategies based on this pathway, including exogenous NO supplementation (e.g., dietary nitrates or NO donor drugs), gene therapy, targeted delivery systems incorporating nanotechnology, and combination therapies with other medications. These strategies are all designed to enhance treatment precision and bioavailability. Finally, we summarize current research limitations and highlight potential directions for future investigations. We conclude that an in-depth exploration of the nitrate-nitrite-NO pathway provides strong theoretical foundations and novel perspectives for developing innovative treatments targeting neuroinflammation and cognitive impairment after ischemic stroke.

Indexed as

Cognitive DysfunctionIschemic StrokeNeuroinflammatory DiseasesNitratesNitric OxideNitritesAnimalsHumansSignal TransductionNitratesNitric OxideNitritesischemic strokeneuroinflammationneuroprotectionnitrate-nitrite pathwaynitric oxide

Identifiers

PMID41948314
PMCPMC13050728

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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.