Evidence map›Paper›PMID 42345099›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2026

Extracellular Mitochondria Mediate Endothelial Injury After Traumatic Brain Injury.

Lujia Tang, Yafan Liu, Kaifeng Pang, Yang Li, Yichi Zhang, Xiaoxi Lu, Xiaoyang Zhang, Pengbo Zhao, Zijian Zhou, Hao Zhang and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

17 authors.

Lujia Tang *Department of Neurosurgery, State Key Laboratory of Experimental Hematology, Tianjin Neurological Institute (L.T., Y. Liu, K.P., Y.Z., X.Z., P.Z., Z. Zhou, H.Z., T.M., J.Z., Z. Zhao), Tianjin Medical University General Hospital, China.
Yafan Liu *Department of Neurosurgery, State Key Laboratory of Experimental Hematology, Tianjin Neurological Institute (L.T., Y. Liu, K.P., Y.Z., X.Z., P.Z., Z. Zhou, H.Z., T.M., J.Z., Z. Zhao), Tianjin Medical University General Hospital, China.ORCID 0000-0002-4200-0098
Kaifeng Pang *Department of Neurosurgery, State Key Laboratory of Experimental Hematology, Tianjin Neurological Institute (L.T., Y. Liu, K.P., Y.Z., X.Z., P.Z., Z. Zhou, H.Z., T.M., J.Z., Z. Zhao), Tianjin Medical University General Hospital, China.
Yang Li *Precision Medicine Center (Y. Li), Tianjin Medical University General Hospital, China.
Yichi Zhang *Department of Neurosurgery, State Key Laboratory of Experimental Hematology, Tianjin Neurological Institute (L.T., Y. Liu, K.P., Y.Z., X.Z., P.Z., Z. Zhou, H.Z., T.M., J.Z., Z. Zhao), Tianjin Medical University General Hospital, China.ORCID 0009-0007-2735-8626
Xiaoxi LuDepartment of Pediatric Hematology & Oncology and Key Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second Hospital, Sichuan University School of Medicine, Chengdu (X.L.).ORCID 0000-0002-5494-589X
Xiaoyang ZhangDepartment of Neurosurgery, State Key Laboratory of Experimental Hematology, Tianjin Neurological Institute (L.T., Y. Liu, K.P., Y.Z., X.Z., P.Z., Z. Zhou, H.Z., T.M., J.Z., Z. Zhao), Tianjin Medical University General Hospital, China.
Pengbo ZhaoDepartment of Neurosurgery, State Key Laboratory of Experimental Hematology, Tianjin Neurological Institute (L.T., Y. Liu, K.P., Y.Z., X.Z., P.Z., Z. Zhou, H.Z., T.M., J.Z., Z. Zhao), Tianjin Medical University General Hospital, China.
Zijian ZhouDepartment of Neurosurgery, State Key Laboratory of Experimental Hematology, Tianjin Neurological Institute (L.T., Y. Liu, K.P., Y.Z., X.Z., P.Z., Z. Zhou, H.Z., T.M., J.Z., Z. Zhao), Tianjin Medical University General Hospital, China.
Hao ZhangDepartment of Neurosurgery, State Key Laboratory of Experimental Hematology, Tianjin Neurological Institute (L.T., Y. Liu, K.P., Y.Z., X.Z., P.Z., Z. Zhou, H.Z., T.M., J.Z., Z. Zhao), Tianjin Medical University General Hospital, China.
Tianrui MaDepartment of Neurosurgery, State Key Laboratory of Experimental Hematology, Tianjin Neurological Institute (L.T., Y. Liu, K.P., Y.Z., X.Z., P.Z., Z. Zhou, H.Z., T.M., J.Z., Z. Zhao), Tianjin Medical University General Hospital, China.
Junrui LiuCollege of Pharmacy, Kunming Medical University, Yunnan, China (J.L.).
Ying FuDepartment of Neurology and Institute of Neurology of First Affiliated Hospital, Institute of Neuroscience and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, China (Y.F.).ORCID 0000-0002-1590-3945
Ming WeiHuanhu Hospital Affiliated to Tianjin Medical University, Tianjin Medical University, China (L.T., M.W.).
Jianning ZhangDepartment of Neurosurgery, State Key Laboratory of Experimental Hematology, Tianjin Neurological Institute (L.T., Y. Liu, K.P., Y.Z., X.Z., P.Z., Z. Zhou, H.Z., T.M., J.Z., Z. Zhao), Tianjin Medical University General Hospital, China.
Jing-Fei DongBloodworks Research Institute, Seattle, WA (J.-f.D., Z. Zhao).ORCID 0000-0001-6379-4133
Zilong ZhaoDepartment of Neurosurgery, State Key Laboratory of Experimental Hematology, Tianjin Neurological Institute (L.T., Y. Liu, K.P., Y.Z., X.Z., P.Z., Z. Zhou, H.Z., T.M., J.Z., Z. Zhao), Tianjin Medical University General Hospital, China.ORCID 0000-0001-8218-6395

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundLocal and systemic endothelial dysfunction following traumatic brain injury (TBI) results in secondary cerebral and pulmonary edema, tissue ischemia, and inflammation. However, the underlying mechanism of the endothelial dysfunction beyond the site of the primary trauma remains poorly understood. Morphologically intact and metabolically active extracellular mitochondria (exMt) accounted for 55.2% of brain-derived extracellular vesicles found in the peripheral blood of mice subjected to severe TBI. This observation led us to investigate the role of exMt in TBI-induced secondary endothelial injury.

methodsWe measured circulating exMt in patients with TBI and mice subjected to TBI and examined the effects of exMt on endothelial cells in vitro and in vivo. Mechanistic studies involved evaluating Cavin-1-dependent endocytosis of exMt and its downstream effects on endothelial cells, including mitophagy activation, lysosomal dysfunction, and apoptosis. The findings were validated in Cavin-1 knockdown endothelial cells and Cavin-1-deficient mice.

resultsHere, we report the detection of high levels of exMt in the peripheral blood samples from patients with TBI. These circulating exMt bound to and were endocytosed by endothelial cells via a Cavin-1-dependent pathway. exMt activated endothelial cells, caused vascular leakage, and promoted an inflammatory response in vitro. Furthermore, noninjured mice infused with exMt developed similar changes in the brain and lungs. exMt endocytosed by endothelial cells activated mitophagy and promoted the formation of mitophagosomes but impaired lysosomal function, leading to endothelial cell apoptosis.

conclusionsResults from this study demonstrate a novel subcellular mechanism for exMt-induced endothelial dysfunction during acute TBI.

Indexed as

Brain Injuries, TraumaticEndothelial CellsEndothelium, VascularExtracellular VesiclesMitochondriaAnimalsApoptosisCapillary PermeabilityCells, CulturedDisease Models, AnimalEndocytosisHumansLysosomesMaleMiceMice, Inbred C57BLbrain injuries, traumaticendothelial cellsmitochondriamitophagyreactive oxygen species

Identifiers

PMID42345099
PMCPMC13384384

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

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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 Socratic graph.