Evidence map›Paper›PMID 34666797›Full record

ArticleJournal of neuroinflammation2021

HMGB1 mediates cognitive impairment caused by the NLRP3 inflammasome in the late stage of traumatic brain injury.

Si-Wei Tan, Yan Zhao, Ping Li, Ya-Lei Ning, Zhi-Zhong Huang, Nan Yang, Dong Liu, Yuan-Guo Zhou

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

29 citing papers in PubMed, 54 citations in OpenAlex.

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  8. HMGB1: key mediator in digestive system diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025
    Review
  9. Clinical and biochemical assessments of circulating High Mobility Group Box Protein1 in children with epilepsy: relation to cognitive function and drug responsiveness.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025
    Article
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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 1 institution in 1 country.

Si-Wei TanState Key Laboratory of Trauma, Burns and Combined Injury, Department of Occupational Disease, Daping Hospital, Army Medical University, Chongqing, China.
Yan ZhaoState Key Laboratory of Trauma, Burns and Combined Injury, Department of Occupational Disease, Daping Hospital, Army Medical University, Chongqing, China.
Ping LiState Key Laboratory of Trauma, Burns and Combined Injury, Department of Occupational Disease, Daping Hospital, Army Medical University, Chongqing, China.
Ya-Lei NingState Key Laboratory of Trauma, Burns and Combined Injury, Department of Occupational Disease, Daping Hospital, Army Medical University, Chongqing, China.
Zhi-Zhong HuangState Key Laboratory of Trauma, Burns and Combined Injury, Department of Occupational Disease, Daping Hospital, Army Medical University, Chongqing, China.
Nan YangState Key Laboratory of Trauma, Burns and Combined Injury, Department of Occupational Disease, Daping Hospital, Army Medical University, Chongqing, China.
Dong LiuMedical Center of Trauma and War Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Daping Hospital, Army Medical University, Chongqing, China.
Yuan-Guo ZhouState Key Laboratory of Trauma, Burns and Combined Injury, Department of Occupational Disease, Daping Hospital, Army Medical University, Chongqing, China. yuanguo.zhou@gmail.com.ORCID http://orcid.org/0000-0002-9912-7970
Army Medical University · CN

Funding

National Natural Science Foundation of China 31771118Third Military Medical University 2016XYY11
6 · The paper itself

Abstract

backgroundCognitive impairment in the late stage of traumatic brain injury (TBI) is associated with the NOD-, LRR and pyrin domain-containing protein 3 (NLRP3) inflammasome, which plays an important role in neuroinflammation. Although classical inflammatory pathways have been well-documented in the late stage of TBI (4-8 weeks post-injury), the mechanism by which the NLRP3 inflammasome impairs cognition is still unclear.

methodsMice lacking the gene encoding for NLRP3 (NLRP3-knockout mice) and their wild-type littermates were used in a controlled cortical impact model of TBI. Levels of NLRP3 inflammasome and inflammatory factors such as IL-1β and HMGB1 were detected in post-injury hippocampal tissue, as well as long-term potentiation. Behaviors were assessed by T-maze test, novel object recognition, and nesting tests. Glycyrrhizin was used to antagonize HMGB1. Calcium imaging were performed on primary neuronal cultures.

resultsBy using the NLRP3-knockout TBI model, we found that the continuous activation of the NLRP3 inflammasome and high mobility group box 1 (HMGB1) release were closely related to cognitive impairment. We also found that inhibition of HMGB1 improved LTP reduction and cognitive function by increasing the phosphorylation level of the NMDAR1 subunit at serine 896 while reducing NLRP3 inflammasome activation.

conclusionNLRP3 inflammasome damages memory in the late stage of TBI primarily through HMGB1 upregulation and provides an explanation for the long-term progression of cognitive dysfunction.

Indexed as

AnimalsBrain Injuries, TraumaticCells, CulturedCerebral CortexCoculture TechniquesCognitive DysfunctionExcitatory Postsynaptic PotentialsHippocampusHMGB1 ProteinMaleMiceMice, 129 StrainMice, Inbred C57BLMice, KnockoutNLR Family, Pyrin Domain-Containing 3 ProteinOrgan Culture TechniquesHMGB1 ProteinHMGB1 protein, mouseNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseCognitive dysfunctionHMGB1NLRP3 inflammasomeTraumatic brain injury

Identifiers

PMID34666797
PMCPMC8527642
OpenAlexW3207209445

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.