Journal Article Ppublish
PubMed: 40146000 DOI: 10.4103/NRR.NRR-D-24-01269
Blood-brain barrier disruption and neuroinflammation in the hippocampus of a cardiac arrest porcine model: Single-cell RNA sequencing analysis.
Neural Regen Res 21(2):742-755
Authors: Tangxing Jiang, Yaning Li, Hehui Liu, Yijun Sun, Huidan Zhang, Qirui Zhang, Shuyao Tang, Xu Niu, Han Du, Yinxia Yu, Hongwei Yue, Yunyun Guo, Yuguo Chen, Feng Xu
Affiliations
- Department of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, Shandong Province, China. Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan, Shandong Province, China. Medical and Pharmaceutical Basic Research Innovation Center of Emergency and Critical Care Medicine, China's Ministry of Education, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan, Shandong Province, China. NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, Qilu Hospital of Shandong University, Jinan, Shandong Province, China. National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, Shandong Province, China.
Abstract
JOURNAL/nrgr/04.03/01300535-202602000-00043/figure1/v/2025-05-05T160104Z/r/image-tiff Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality. Despite advancements in resuscitation science, our limited understanding of the cellular and molecular mechanisms underlying post-cardiac arrest brain injury have hindered the development of effective neuroprotective strategies. Previous studies primarily focused on neuronal death, potentially overlooking the contributions of non-neuronal cells and intercellular communication to the pathophysiology of cardiac arrest-induced brain injury. To address these gaps, we hypothesized that single-cell transcriptomic analysis could uncover previously unidentified cellular subpopulations, altered cell communication networks, and novel molecular mechanisms involved in post-cardiac arrest brain injury. In this study, we performed a single-cell transcriptomic analysis of the hippocampus from pigs with ventricular fibrillation-induced cardiac arrest at 6 and 24 hours following the return of spontaneous circulation, and from sham control pigs. Sequencing results revealed changes in the proportions of different cell types, suggesting post-arrest disruption in the blood-brain barrier and infiltration of neutrophils. These results were validated through western blotting, quantitative reverse transcription-polymerase chain reaction, and immunofluorescence staining. We also identified and validated a unique subcluster of activated microglia with high expression of S100A8, which increased over time following cardiac arrest. This subcluster simultaneously exhibited significant M1/M2 polarization and expressed key functional genes related to chemokines and interleukins. Additionally, we revealed the post-cardiac arrest dysfunction of oligodendrocytes and the differentiation of oligodendrocyte precursor cells into oligodendrocytes. Cell communication analysis identified enhanced post-cardiac arrest communication between neutrophils and microglia that was mediated by neutrophil-derived resistin, driving pro-inflammatory microglial polarization. Our findings provide a comprehensive single-cell map of the post-cardiac arrest hippocampus, offering potential novel targets for neuroprotection and repair following cardiac arrest.
MeSH
Hippocampus, Blood-Brain Barrier, Microglia, Cells, Brain Injuries, Oligodendroglia, Heart Arrest, Induced, Blood, Communication, Brain, Neutrophils, Heart Arrest, Oligodendrocyte Precursor Cells, Rna