Blood–brain barrier disruption and neuroinflammation in the hippocampus of a cardiac arrest porcine model: Single-cell RNA sequencing analysis
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 o...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Medknow Publications
2026-02-01
|
| Series: | Neural Regeneration Research |
| Subjects: | |
| Online Access: | https://journals.lww.com/10.4103/NRR.NRR-D-24-01269 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850236188282060800 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Tangxing Jiang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c8492a723c2c49cb8f9d36c6901102cd |
| institution | OA Journals |
| issn | 1673-5374 1876-7958 |
| language | English |
| publishDate | 2026-02-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj-art-c8492a723c2c49cb8f9d36c6901102cd2025-08-20T02:02:01ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53741876-79582026-02-0121274275510.4103/NRR.NRR-D-24-01269Blood–brain barrier disruption and neuroinflammation in the hippocampus of a cardiac arrest porcine model: Single-cell RNA sequencing analysisTangxing JiangYaning LiHehui LiuYijun SunHuidan ZhangQirui ZhangShuyao TangXu NiuHan DuYinxia YuHongwei YueYunyun GuoYuguo ChenFeng XuGlobal 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.https://journals.lww.com/10.4103/NRR.NRR-D-24-01269blood–brain barrier disruptioncardiac arresthippocampusmicroglianeuroinflammationneuroprotectionneutrophiloligodendrocyte dysfunctions100a8single-cell rna sequencing |
| spellingShingle | 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 Blood–brain barrier disruption and neuroinflammation in the hippocampus of a cardiac arrest porcine model: Single-cell RNA sequencing analysis Neural Regeneration Research blood–brain barrier disruption cardiac arrest hippocampus microglia neuroinflammation neuroprotection neutrophil oligodendrocyte dysfunction s100a8 single-cell rna sequencing |
| title | Blood–brain barrier disruption and neuroinflammation in the hippocampus of a cardiac arrest porcine model: Single-cell RNA sequencing analysis |
| title_full | Blood–brain barrier disruption and neuroinflammation in the hippocampus of a cardiac arrest porcine model: Single-cell RNA sequencing analysis |
| title_fullStr | Blood–brain barrier disruption and neuroinflammation in the hippocampus of a cardiac arrest porcine model: Single-cell RNA sequencing analysis |
| title_full_unstemmed | Blood–brain barrier disruption and neuroinflammation in the hippocampus of a cardiac arrest porcine model: Single-cell RNA sequencing analysis |
| title_short | Blood–brain barrier disruption and neuroinflammation in the hippocampus of a cardiac arrest porcine model: Single-cell RNA sequencing analysis |
| title_sort | blood brain barrier disruption and neuroinflammation in the hippocampus of a cardiac arrest porcine model single cell rna sequencing analysis |
| topic | blood–brain barrier disruption cardiac arrest hippocampus microglia neuroinflammation neuroprotection neutrophil oligodendrocyte dysfunction s100a8 single-cell rna sequencing |
| url | https://journals.lww.com/10.4103/NRR.NRR-D-24-01269 |
| work_keys_str_mv | AT tangxingjiang bloodbrainbarrierdisruptionandneuroinflammationinthehippocampusofacardiacarrestporcinemodelsinglecellrnasequencinganalysis AT yaningli bloodbrainbarrierdisruptionandneuroinflammationinthehippocampusofacardiacarrestporcinemodelsinglecellrnasequencinganalysis AT hehuiliu bloodbrainbarrierdisruptionandneuroinflammationinthehippocampusofacardiacarrestporcinemodelsinglecellrnasequencinganalysis AT yijunsun bloodbrainbarrierdisruptionandneuroinflammationinthehippocampusofacardiacarrestporcinemodelsinglecellrnasequencinganalysis AT huidanzhang bloodbrainbarrierdisruptionandneuroinflammationinthehippocampusofacardiacarrestporcinemodelsinglecellrnasequencinganalysis AT qiruizhang bloodbrainbarrierdisruptionandneuroinflammationinthehippocampusofacardiacarrestporcinemodelsinglecellrnasequencinganalysis AT shuyaotang bloodbrainbarrierdisruptionandneuroinflammationinthehippocampusofacardiacarrestporcinemodelsinglecellrnasequencinganalysis AT xuniu bloodbrainbarrierdisruptionandneuroinflammationinthehippocampusofacardiacarrestporcinemodelsinglecellrnasequencinganalysis AT handu bloodbrainbarrierdisruptionandneuroinflammationinthehippocampusofacardiacarrestporcinemodelsinglecellrnasequencinganalysis AT yinxiayu bloodbrainbarrierdisruptionandneuroinflammationinthehippocampusofacardiacarrestporcinemodelsinglecellrnasequencinganalysis AT hongweiyue bloodbrainbarrierdisruptionandneuroinflammationinthehippocampusofacardiacarrestporcinemodelsinglecellrnasequencinganalysis AT yunyunguo bloodbrainbarrierdisruptionandneuroinflammationinthehippocampusofacardiacarrestporcinemodelsinglecellrnasequencinganalysis AT yuguochen bloodbrainbarrierdisruptionandneuroinflammationinthehippocampusofacardiacarrestporcinemodelsinglecellrnasequencinganalysis AT fengxu bloodbrainbarrierdisruptionandneuroinflammationinthehippocampusofacardiacarrestporcinemodelsinglecellrnasequencinganalysis |