Evidence map›Paper›PMID 40934970›Full record

ArticleJournal of advanced research2026

Targeting CIRP and IL-6R-mediated microglial inflammation to improve outcomes in intracerebral hemorrhage.

Lisha Ye, Xiaoyan Tang, Fangming Liu, Tianjiao Wei, Ting Xu, Zhenglin Jiang, Lihua Xu, Chao Xiang, Xiaoyu Yuan, Lihua Shen and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of advanced research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. 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

13 authors.

Lisha YeDepartment of Neurophysiology and Neuropharmacology, Institute of Special Environmental Medicine and Co-innovation Center of Neuroregeneration, Nantong University, 9 Seyuan Road, Nantong, Jiangsu 226019, China; Beijing Institute of Brain Disorders, No. 10 Xitoutiao, Beijing 100069, China.
Xiaoyan TangDepartment of Neurophysiology and Neuropharmacology, Institute of Special Environmental Medicine and Co-innovation Center of Neuroregeneration, Nantong University, 9 Seyuan Road, Nantong, Jiangsu 226019, China.
Fangming LiuDepartment of Neurophysiology and Neuropharmacology, Institute of Special Environmental Medicine and Co-innovation Center of Neuroregeneration, Nantong University, 9 Seyuan Road, Nantong, Jiangsu 226019, China.
Tianjiao WeiDepartment of Neurophysiology and Neuropharmacology, Institute of Special Environmental Medicine and Co-innovation Center of Neuroregeneration, Nantong University, 9 Seyuan Road, Nantong, Jiangsu 226019, China.
Ting XuDepartment of Neurophysiology and Neuropharmacology, Institute of Special Environmental Medicine and Co-innovation Center of Neuroregeneration, Nantong University, 9 Seyuan Road, Nantong, Jiangsu 226019, China.
Zhenglin JiangDepartment of Neurophysiology and Neuropharmacology, Institute of Special Environmental Medicine and Co-innovation Center of Neuroregeneration, Nantong University, 9 Seyuan Road, Nantong, Jiangsu 226019, China.
Lihua XuDepartment of Neurophysiology and Neuropharmacology, Institute of Special Environmental Medicine and Co-innovation Center of Neuroregeneration, Nantong University, 9 Seyuan Road, Nantong, Jiangsu 226019, China.
Chao XiangDepartment of Neurosurgery, Zhengzhou University People's Hospital (Henan Provincial People's Hospital), 7 Weiwu Road, Zhengzhou, Henan 450000, China.
Xiaoyu YuanDepartment of Emergency, Affiliated Hospital of Nantong University, Nantong 226001, China.
Lihua ShenDepartment of Neurology, Affiliated Hospital of Nantong University, Nantong 226001, China.
Jianjun GuDepartment of Neurosurgery, Zhengzhou University People's Hospital (Henan Provincial People's Hospital), 7 Weiwu Road, Zhengzhou, Henan 450000, China. Electronic address: gujianjundt@163.com.
Qianqian LuoDepartment of Neurophysiology and Neuropharmacology, Institute of Special Environmental Medicine and Co-innovation Center of Neuroregeneration, Nantong University, 9 Seyuan Road, Nantong, Jiangsu 226019, China. Electronic address: qianqianluo@ntu.edu.cn.
Guohua WangBeijing Institute of Brain Disorders, No. 10 Xitoutiao, Beijing 100069, China; Department of Neurology, Xuanwu Hospital, Capital Medical University, 45 Changchun Street, Beijing 100053, China. Electronic address: wangguohua@xwhosp.org.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionCold-inducible RNA-binding protein (CIRP) is an emerging inflammatory mediator implicated in neuronal injury following intracerebral hemorrhage (ICH). However, the underlying mechanisms by which CIRP contributes to neuroinflammation remain unclear.

objectivesTo investigate the role of neuron-derived CIRP in activating microglial inflammation via IL-6 receptor (IL-6R) signaling after ICH and to evaluate the therapeutic potential of targeting CIRP and IL-6R using a designed peptide inhibitor.

methodsSingle-cell RNA sequencing was performed to identify key genes and pathways involved in microglial responses post-ICH. A peptide inhibitor, Tat-CIRP-CMA (TCC), was designed to target CIRP and IL-6R and tested in both in vitro (oxygen-glucose deprivation model) and in vivo (rat ICH model) systems. The effects of TCC on neuronal CIRP release, microglial activation, inflammation, and phagocytic function were assessed. A microglia-specific IL-6Rα knockout mouse model was used to further validate the functional relevance of the IL-6R/ signal transducer and activator of transcription 3 (STAT3) pathway. Clinical analysis of human ICH patients evaluated the correlation between peripheral CIRP expression and infarct volume.

resultsNeuron-derived CIRP activates microglia through IL-6R and downstream STAT3 signaling, driving pro-inflammatory responses in ICH. TCC treatment significantly reduced neuronal CIRP release, suppressed microglial activation, and decreased inflammatory cytokine levels. TCC inhibited the IL-6R /STAT3 pathway and enhanced microglial phagocytosis of red blood cells. Microglia-specific IL-6Rα deletion mirrored the anti-inflammatory and neuroprotective effects observed with TCC, reducing hematoma volume and improving sensory and behavioral outcomes. In human ICH patients, elevated peripheral CIRP expression positively correlated with infarct volume, supporting its value as a biomarker for ICH severity and prognosis.

conclusionCIRP plays a pivotal role in post-ICH neuroinflammation by acting on IL-6R in microglia. The TCC peptide inhibitor effectively reduces CIRP-IL-6R mediated inflammation and supports neuroprotection. CIRP represents a promising therapeutic target and biomarker for ICH.

Indexed as

Cerebral HemorrhageInflammationMicrogliaReceptors, Interleukin-6RNA-Binding ProteinsAnimalsDisease Models, AnimalHumansMaleMiceMice, KnockoutRatsSignal TransductionSTAT3 Transcription FactorCIRBP protein, humanCirbp protein, mouseReceptors, Interleukin-6RNA-Binding ProteinsSTAT3 Transcription FactorCold-inducible RNA-binding proteinsIntracerebral hemorrhageMicroglial polarizationNeuroinflammationTat peptides

Identifiers

PMID40934970
PMCPMC13227277

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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.