Targeting Ninjurin-1-Mediated Microglial Pyroptosis Attenuates Neuroinflammation and Neuronal Injury Following Intracerebral Hemorrhage.
4 affiliations
- 1Department of Trauma Center, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, Hunan, People's Republic of China.
- 2Department of Emergency, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, Hunan, People's Republic of China.
- 3Health Management Center, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, Hunan, People's Republic of China.
- 4Department of General Surgery, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, Hunan, People's Republic of China.
Abstract
Objective
This study aims to delineate the pathophysiological contribution of Ninjurin-1 (Ninj1) to secondary neural injury following intracerebral hemorrhage (ICH), specifically elucidating its function in microglial pyroptosis and its upstream transcriptional governance by nuclear factor-kappa B (NF-κB).Methods
Candidate targets were initially identified via in silico transcriptomic profiling. We subsequently employed a collagenase-induced murine ICH paradigm alongside hemin-challenged microglia. Mechanistic pathways were interrogated utilizing targeted genetic silencing (in vivo siRNA and in vitro shRNA) and pharmacological blockade. Disease phenotypes-encompassing pyroptotic execution, neuroinflammation, and collateral neuronal death-were quantified via immunoblotting, molecular assays, and histopathology. The upstream regulatory architecture was validated through ChIP-qPCR, EMSA, and dual-luciferase reporter assays.Results
Bioinformatic screening highlighted Ninj1 as a prominently upregulated candidate transcript post-ICH, a finding corroborated by robust induction in both in vivo and in vitro hemorrhagic models. Through prophylactic in vivo target validation, Ninj1 depletion restricted perihematomal edema and preserved sensorimotor function. Mechanistically, suppressing Ninj1 abrogated the microglial pyroptotic cascade and mitigated collateral neurotoxicity. Furthermore, NF-κB was shown to transcriptionally activate NLRP3 and Ninj1, although direct promoter enrichment in the ChIP-qPCR assay was statistically significant only for the Nlrp3 locus.Conclusions
Ninj1 functions as a terminal executioner of microglial pyroptosis and a critical amplifier of post-ICH neuroinflammation. Governed by a coordinated NF-κB-dependent transcriptional program alongside NLRP3, this signaling axis exacerbates secondary brain injury, positioning Ninj1 as a viable molecular candidate for neuroprotective target validation.
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BibTeX
@article{peng2026targeting,
title = {{Targeting Ninjurin-1-Mediated Microglial Pyroptosis Attenuates Neuroinflammation and Neuronal Injury Following Intracerebral Hemorrhage.}},
author = {Liqiang Peng and Aosheng Peng and Hui Zhu and Ting Sun and Pan Liu and Ting Qi},
journal = {Brain and behavior},
year = {2026},
month = nov,
doi = {10.1002/brb3.71862},
url = {https://europepmc.org/article/MED/42968342},
note = {CC BY},
}
RIS
TY - JOUR
TI - Targeting Ninjurin-1-Mediated Microglial Pyroptosis Attenuates Neuroinflammation and Neuronal Injury Following Intracerebral Hemorrhage.
AU - Liqiang Peng
AU - Aosheng Peng
AU - Hui Zhu
AU - Ting Sun
AU - Pan Liu
AU - Ting Qi
PY - 2026
DA - 2026/11/01
JO - Brain and behavior
DO - 10.1002/brb3.71862
UR - https://europepmc.org/article/MED/42968342
AB - Objective This study aims to delineate the pathophysiological contribution of Ninjurin-1 (Ninj1) to secondary neural injury following intracerebral hemorrhage (ICH), specifically elucidating its function in microglial pyroptosis and its upstream transcriptional governance by nuclear factor-kappa B (NF-κB).Methods Candidate targets were initially identified via in silico transcriptomic profiling. We subsequently employed a collagenase-induced murine ICH paradigm alongside hemin-challenged microglia. Mechanistic pathways were interrogated utilizing targeted genetic silencing (in vivo siRNA and in vitro shRNA) and pharmacological blockade. Disease phenotypes-encompassing pyroptotic execution, neuroinflammation, and collateral neuronal death-were quantified via immunoblotting, molecular assays, and histopathology. The upstream regulatory architecture was validated through ChIP-qPCR, EMSA, and dual-luciferase reporter assays.Results Bioinformatic screening highlighted Ninj1 as a prominently upregulated candidate transcript post-ICH, a finding corroborated by robust induction in both in vivo and in vitro hemorrhagic models. Through prophylactic in vivo target validation, Ninj1 depletion restricted perihematomal edema and preserved sensorimotor function. Mechanistically, suppressing Ninj1 abrogated the microglial pyroptotic cascade and mitigated collateral neurotoxicity. Furthermore, NF-κB was shown to transcriptionally activate NLRP3 and Ninj1, although direct promoter enrichment in the ChIP-qPCR assay was statistically significant only for the Nlrp3 locus.Conclusions Ninj1 functions as a terminal executioner of microglial pyroptosis and a critical amplifier of post-ICH neuroinflammation. Governed by a coordinated NF-κB-dependent transcriptional program alongside NLRP3, this signaling axis exacerbates secondary brain injury, positioning Ninj1 as a viable molecular candidate for neuroprotective target validation.
SN - 2162-3279
ER -