A minimally invasive thrombotic model to study stroke in awake mice
Abstract Experimental stroke models in rodents are essential for mechanistic studies and therapeutic development. However, these models have several limitations negatively impacting their translational relevance. Here we aimed to develop a minimally invasive thrombotic stroke model through magnetic...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59617-1 |
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| author | Kimberly Marks Sung-Ji Ahn Ninamma Rai Antoine Anfray Costantino Iadecola Josef Anrather |
| author_facet | Kimberly Marks Sung-Ji Ahn Ninamma Rai Antoine Anfray Costantino Iadecola Josef Anrather |
| author_sort | Kimberly Marks |
| collection | DOAJ |
| description | Abstract Experimental stroke models in rodents are essential for mechanistic studies and therapeutic development. However, these models have several limitations negatively impacting their translational relevance. Here we aimed to develop a minimally invasive thrombotic stroke model through magnetic particle delivery that does not require craniotomy, is amenable to reperfusion therapy, can be combined with in vivo imaging modalities, and can be performed in awake mice. We found that the model results in reproducible cortical infarcts within the middle cerebral artery (MCA) territory with cytologic and immune changes similar to that observed with more invasive distal MCA occlusion models. Importantly, the injury produced by the model was ameliorated by tissue plasminogen activator (tPA) administration. We also show that MCA occlusion in awake animals results in bigger ischemic lesions independent of day/night cycle. Magnetic particle delivery had no overt effects on physiologic parameters and systemic immune biomarkers. In conclusion, we developed a novel stroke model in mice that fulfills many requirements for modeling human stroke. |
| format | Article |
| id | doaj-art-a7b620d26b504352bc85dfb4053b3be5 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-a7b620d26b504352bc85dfb4053b3be52025-08-20T03:08:43ZengNature PortfolioNature Communications2041-17232025-05-0116111610.1038/s41467-025-59617-1A minimally invasive thrombotic model to study stroke in awake miceKimberly Marks0Sung-Ji Ahn1Ninamma Rai2Antoine Anfray3Costantino Iadecola4Josef Anrather5Feil Family Brain and Mind Research Institute, Weill Cornell MedicineFeil Family Brain and Mind Research Institute, Weill Cornell MedicineFeil Family Brain and Mind Research Institute, Weill Cornell MedicineFeil Family Brain and Mind Research Institute, Weill Cornell MedicineFeil Family Brain and Mind Research Institute, Weill Cornell MedicineFeil Family Brain and Mind Research Institute, Weill Cornell MedicineAbstract Experimental stroke models in rodents are essential for mechanistic studies and therapeutic development. However, these models have several limitations negatively impacting their translational relevance. Here we aimed to develop a minimally invasive thrombotic stroke model through magnetic particle delivery that does not require craniotomy, is amenable to reperfusion therapy, can be combined with in vivo imaging modalities, and can be performed in awake mice. We found that the model results in reproducible cortical infarcts within the middle cerebral artery (MCA) territory with cytologic and immune changes similar to that observed with more invasive distal MCA occlusion models. Importantly, the injury produced by the model was ameliorated by tissue plasminogen activator (tPA) administration. We also show that MCA occlusion in awake animals results in bigger ischemic lesions independent of day/night cycle. Magnetic particle delivery had no overt effects on physiologic parameters and systemic immune biomarkers. In conclusion, we developed a novel stroke model in mice that fulfills many requirements for modeling human stroke.https://doi.org/10.1038/s41467-025-59617-1 |
| spellingShingle | Kimberly Marks Sung-Ji Ahn Ninamma Rai Antoine Anfray Costantino Iadecola Josef Anrather A minimally invasive thrombotic model to study stroke in awake mice Nature Communications |
| title | A minimally invasive thrombotic model to study stroke in awake mice |
| title_full | A minimally invasive thrombotic model to study stroke in awake mice |
| title_fullStr | A minimally invasive thrombotic model to study stroke in awake mice |
| title_full_unstemmed | A minimally invasive thrombotic model to study stroke in awake mice |
| title_short | A minimally invasive thrombotic model to study stroke in awake mice |
| title_sort | minimally invasive thrombotic model to study stroke in awake mice |
| url | https://doi.org/10.1038/s41467-025-59617-1 |
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