Evidence map›Paper›PMID 41388303›Full record

ArticleJournal of neuroinflammation2025

SIRT2 Inhibition promotes microglia LC3-associated phagocytosis via NRF2/CD36 after the experimental subarachnoid hemorrhage.

Bin Sheng, Xiangxin Chen, Tao Tao, Jiaqing Sun, Wei Li, Lingyun Wu, Zheng Peng, Xiaojian Li, Zhengxu Zhou, Qian Yu and 7 more

Erratum issuedAbstract 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. An erratum has been issued. 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. Article
  2. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Bin Sheng *Department of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Neurosurgical Institute of Nanjing University, Nanjing, China.
Xiangxin Chen *Department of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Neurosurgical Institute of Nanjing University, Nanjing, China.
Tao Tao *Department of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Neurosurgical Institute of Nanjing University, Nanjing, China.
Jiaqing Sun *Department of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Neurosurgical Institute of Nanjing University, Nanjing, China.
Wei LiDepartment of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Neurosurgical Institute of Nanjing University, Nanjing, China.
Lingyun WuDepartment of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Neurosurgical Institute of Nanjing University, Nanjing, China.
Zheng PengDepartment of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Neurosurgical Institute of Nanjing University, Nanjing, China.
Xiaojian LiDepartment of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Neurosurgical Institute of Nanjing University, Nanjing, China.
Zhengxu ZhouDepartment of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Neurosurgical Institute of Nanjing University, Nanjing, China.
Qian YuDepartment of Physiology and Pharmacology, Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, CA, 92354, USA.
Yeping LingDepartment of Physiology and Pharmacology, Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, CA, 92354, USA.
Prativa SherchanDepartment of Physiology and Pharmacology, Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, CA, 92354, USA.
Jerry J FloresDepartment of Physiology and Pharmacology, Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, CA, 92354, USA.
Jiping TangDepartment of Physiology and Pharmacology, Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, CA, 92354, USA.
Lei HuangDepartment of Physiology and Pharmacology, Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, CA, 92354, USA. lhuang@llu.edu.
Chunhua HangDepartment of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Neurosurgical Institute of Nanjing University, Nanjing, China. hang_neurosurgery@163.com.
John H ZhangDepartment of Physiology and Pharmacology, Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, CA, 92354, USA. johnzhang3910@yahoo.com.

Funding

Novel neurovascular protective mechanisms of PEDF after subarachnoid hemorrhageR01NS117179 · NINDS · LOMA LINDA UNIVERSITY · 2023 to 2025
$1.2M
National Natural Science Foundation of China 82130037National Natural Science Foundation of China 82301485NIH HHS NIH NS 117179NINDS NIH HHS R01 NS117179
6 · The paper itself

Abstract

backgroundSubarachnoid hemorrhage (SAH) results in the accumulation of blood in the subarachnoid space, which can trigger inflammatory responses and oxidative damage, thereby exacerbating secondary brain injury. Microglia play a critical role in clearing hematomas and cellular debris during pathological recovery. This study aimed to investigate the regulatory role of SIRT2 in phagocytic function and its potential mechanisms.

methodsThe SAH model of endovascular perforation in Sprague-Dawley (SD) rats and in vitro model of primary microglia culture with Oxygenated hemoglobin (OxyHb) stimulation were used. Flow cytometry, Western blot, immunofluorescence, ELISA were used to detect the microglial phagocytic ability, expressions of SRIT2 and LC3-associated phagocytosis (LAP)-related proteins. Molecular docking, and immunoprecipitation were used to explore the underlying mechanism of the SIRT2/NRF2/CD36 signaling pathway. Behavioral experiments were conducted to evaluate changes in neurological function.

resultsWithin 24 h after SAH, the expression of SIRT2 in brain and microglia was significantly increased, while the phagocytic ability and the expression of LAP-related proteins Rubicon, NOX2 were decreased. After inhibiting SIRT2, microglial LAP function was enhanced and the phagocytic index was increased. Mechanistically, SIRT2 inhibited NRF2 nuclear translocation by deacetylation, thereby downregulating CD36 expression and suppressing microglia LAP. ML385 reversed the enhancement of LAP and the improvement in neurological function induced by SIRT2 inhibition.

conclusionSIRT2 suppresses microglial LAP by deacetylating NRF2, thereby impairing its nuclear translocation and reducing transcriptional expression of CD36 subsequently. Inhibiting SIRT2 may effectively enhance microglial LAP function via activating NRF2/CD36 pathway, promoting blood clearance and improving neurological prognosis after SAH.

Indexed as

CD36 AntigensMicrogliaMicrotubule-Associated ProteinsNF-E2-Related Factor 2PhagocytosisSirtuin 2Subarachnoid HemorrhageAnimalsCells, CulturedDisease Models, AnimalMaleRatsRats, Sprague-DawleySignal TransductionCD36 AntigensMicrotubule-Associated ProteinsNfe2l2 protein, ratNF-E2-Related Factor 2Sirt2 protein, ratSirtuin 2LAPMicrogliaPhagocytosisSIRT2Subarachnoid hemorrhage

Identifiers

PMID41388303
PMCPMC12825238

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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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 Socratic graph.