Evidence map›Paper›PMID 42337592›Full record

ArticleJournal of neuroinflammation2026

PDZD8 overexpression alleviates early brain injury via regulating MERCs integrity after experimental subarachnoid hemorrhage.

Peng Deng, Xin Wu, Yangyang Liu, Bingyi Song, Xi Liu, Xiao Yang, Han Luo, Jiabei Peng, Haiying Li, Zhong Wang and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neuroinflammation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

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0 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

12 authors.

Peng Deng *Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, 188 Shizi Street, Suzhou, 215006, China.
Xin Wu *Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, 188 Shizi Street, Suzhou, 215006, China.
Yangyang Liu *Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, 188 Shizi Street, Suzhou, 215006, China.
Bingyi SongDepartment of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, 188 Shizi Street, Suzhou, 215006, China.
Xi LiuDepartment of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, 188 Shizi Street, Suzhou, 215006, China.
Xiao YangDepartment of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, 188 Shizi Street, Suzhou, 215006, China.
Han LuoDepartment of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, 188 Shizi Street, Suzhou, 215006, China.
Jiabei PengDepartment of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, 188 Shizi Street, Suzhou, 215006, China.
Haiying LiDepartment of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, 188 Shizi Street, Suzhou, 215006, China.
Zhong WangDepartment of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, 188 Shizi Street, Suzhou, 215006, China.
Zongqi WangDepartment of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, 188 Shizi Street, Suzhou, 215006, China. wangzongqi1992@suda.edu.cn.
Wen LiDepartment of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, 188 Shizi Street, Suzhou, 215006, China. liwenguanyun@163.com.

Funding

Gusu Talent Program GSWS2023022
6 · The paper itself

Abstract

Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular disorder with high acute mortality and long-term neurological disability, and early brain injury (EBI) characterized by mitochondrial dysfunction, oxidative stress, and neuronal apoptosis is a pivotal determinant of poor prognosis. Mitochondria-endoplasmic reticulum contact sites (MERCs) are specialized membrane domains essential for maintaining cellular homeostasis via calcium trafficking and lipid exchange, but their regulatory mechanisms in SAH-induced EBI remain largely undefined. Here, we investigated the role and underlying mechanism of PDZD8, a core MERCs-stabilizing protein, in SAH pathogenesis using in vivo endovascular perforation models of male C57BL/6 mice and in vitro oxyhemoglobin (OxyHb)-challenged primary cortical neurons/HT22 cells, combined with PDZD8 overexpression, CRISPR/Cas9-mediated knockout, and C884A site-directed mutagenesis. Results demonstrated that PDZD8 was neuron-specifically downregulated at 48 h post-SAH, which closely correlated with MERCs structural disruption detected by transmission electron microscopy, impaired mitochondrial respiration analyzed via Seahorse assays, excessive reactive oxygen species production, and severe neuronal damage assessed by Nissl staining. PDZD8 overexpression preserved MERCs integrity, restored mitochondrial metabolic balance, mitigated oxidative stress, and ameliorated neurobehavioral deficits evaluated by modified neurological severity scores, rotarod, and open field tests. Mechanistically, SAH-induced PDZD8 downregulation was associated with enhanced global S-nitrosylation and post-translational regulation at cysteine 884 (C884), promoting its ubiquitination and proteasomal degradation, while C884A mutation abrogated this process. Our findings reveal a previously unrecognized mechanism involving S-nitrosylation-associated ubiquitination of PDZD8 in SAH-induced MERCs dysfunction and EBI, highlighting PDZD8 as a promising therapeutic target for SAH treatment.

Indexed as

Brain InjuriesEndoplasmic ReticulumMitochondriaSubarachnoid HemorrhageAnimalsDisease Models, AnimalMaleMiceMice, Inbred C57BLMitochondria Associated MembranesNeuronsOxidative StressEarly Brain Injury (EBI)Mitochondria-Endoplasmic Reticulum Contact Sites (MERCs)PDZD8S-nitrosylationSubarachnoid Hemorrhage (SAH)

Identifiers

PMID42337592
PMCPMC13543607

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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.