Secondary Ischemia Assessment in Murine and Rat Preclinical Subarachnoid Hemorrhage Models: A Systematic Review
Background Delayed cerebral ischemia represents a significant contributor to death and disability following aneurysmal subarachnoid hemorrhage. Although preclinical models have shown promising results, clinical trials have consistently failed to replicate the success of therapeutic strategies. The l...
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| Format: | Article |
| Language: | English |
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Wiley
2024-03-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.123.032694 |
| _version_ | 1797269134910685184 |
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| author | Elias Fürstenau Ute Lindauer Henner Koch Anke Höllig |
| author_facet | Elias Fürstenau Ute Lindauer Henner Koch Anke Höllig |
| author_sort | Elias Fürstenau |
| collection | DOAJ |
| description | Background Delayed cerebral ischemia represents a significant contributor to death and disability following aneurysmal subarachnoid hemorrhage. Although preclinical models have shown promising results, clinical trials have consistently failed to replicate the success of therapeutic strategies. The lack of standardized experimental setups and outcome assessments, particularly regarding secondary vasospastic/ischemic events, may be partly responsible for the translational failure. The study aims to delineate the procedural characteristics and assessment modalities of secondary vasospastic and ischemic events, serving as surrogates for clinically relevant delayed cerebral ischemia, in recent rat and murine subarachnoid hemorrhage models. Methods and Results We conducted a systematic review of rat and murine in vivo subarachnoid hemorrhage studies (published: 2016–2020) using delayed cerebral ischemia/vasospasm as outcome parameters. Our analysis included 102 eligible studies. In murine studies (n=30), the endovascular perforation model was predominantly used, while rat studies primarily employed intracisternal blood injection to mimic subarachnoid hemorrhage. Particularly, the injection models exhibited considerable variation in injection volume, rate, and cerebrospinal fluid withdrawal. Peri‐interventional monitoring was generally inadequately reported across all models, with body temperature and blood pressure being the most frequently documented parameters (62% and 34%, respectively). Vasospastic events were mainly assessed through microscopy of large cerebral arteries. In 90% of the rat and 86% of the murine studies, only male animals were used. Conclusions Our study underscores the substantial heterogeneity in procedural characteristics and outcome assessments of experimental subarachnoid hemorrhage research. To address these challenges, drafting guidelines for standardization and ensuring rigorous control of methodological and experimental quality by funders and journals are essential. Registration URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42022337279. |
| first_indexed | 2024-04-25T01:43:33Z |
| format | Article |
| id | doaj.art-c09f27e5976f4928bb2ca59f33400248 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-04-25T01:43:33Z |
| publishDate | 2024-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-c09f27e5976f4928bb2ca59f334002482024-03-08T02:22:47ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802024-03-0113510.1161/JAHA.123.032694Secondary Ischemia Assessment in Murine and Rat Preclinical Subarachnoid Hemorrhage Models: A Systematic ReviewElias Fürstenau0Ute Lindauer1Henner Koch2Anke Höllig3Department of Neurosurgery University Hospital Aachen, RWTH Aachen University Aachen GermanyDepartment of Neurosurgery University Hospital Aachen, RWTH Aachen University Aachen GermanyDepartment of Epileptology and Neurology RWTH Aachen University Aachen GermanyDepartment of Neurosurgery University Hospital Aachen, RWTH Aachen University Aachen GermanyBackground Delayed cerebral ischemia represents a significant contributor to death and disability following aneurysmal subarachnoid hemorrhage. Although preclinical models have shown promising results, clinical trials have consistently failed to replicate the success of therapeutic strategies. The lack of standardized experimental setups and outcome assessments, particularly regarding secondary vasospastic/ischemic events, may be partly responsible for the translational failure. The study aims to delineate the procedural characteristics and assessment modalities of secondary vasospastic and ischemic events, serving as surrogates for clinically relevant delayed cerebral ischemia, in recent rat and murine subarachnoid hemorrhage models. Methods and Results We conducted a systematic review of rat and murine in vivo subarachnoid hemorrhage studies (published: 2016–2020) using delayed cerebral ischemia/vasospasm as outcome parameters. Our analysis included 102 eligible studies. In murine studies (n=30), the endovascular perforation model was predominantly used, while rat studies primarily employed intracisternal blood injection to mimic subarachnoid hemorrhage. Particularly, the injection models exhibited considerable variation in injection volume, rate, and cerebrospinal fluid withdrawal. Peri‐interventional monitoring was generally inadequately reported across all models, with body temperature and blood pressure being the most frequently documented parameters (62% and 34%, respectively). Vasospastic events were mainly assessed through microscopy of large cerebral arteries. In 90% of the rat and 86% of the murine studies, only male animals were used. Conclusions Our study underscores the substantial heterogeneity in procedural characteristics and outcome assessments of experimental subarachnoid hemorrhage research. To address these challenges, drafting guidelines for standardization and ensuring rigorous control of methodological and experimental quality by funders and journals are essential. Registration URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42022337279.https://www.ahajournals.org/doi/10.1161/JAHA.123.032694preclinical researchquality controlsubarachnoid hemorrhagetranslation |
| spellingShingle | Elias Fürstenau Ute Lindauer Henner Koch Anke Höllig Secondary Ischemia Assessment in Murine and Rat Preclinical Subarachnoid Hemorrhage Models: A Systematic Review Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease preclinical research quality control subarachnoid hemorrhage translation |
| title | Secondary Ischemia Assessment in Murine and Rat Preclinical Subarachnoid Hemorrhage Models: A Systematic Review |
| title_full | Secondary Ischemia Assessment in Murine and Rat Preclinical Subarachnoid Hemorrhage Models: A Systematic Review |
| title_fullStr | Secondary Ischemia Assessment in Murine and Rat Preclinical Subarachnoid Hemorrhage Models: A Systematic Review |
| title_full_unstemmed | Secondary Ischemia Assessment in Murine and Rat Preclinical Subarachnoid Hemorrhage Models: A Systematic Review |
| title_short | Secondary Ischemia Assessment in Murine and Rat Preclinical Subarachnoid Hemorrhage Models: A Systematic Review |
| title_sort | secondary ischemia assessment in murine and rat preclinical subarachnoid hemorrhage models a systematic review |
| topic | preclinical research quality control subarachnoid hemorrhage translation |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.123.032694 |
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