The project carried out a series of systematic reviews and meta‑analyses to quantify how common comorbidities influence stroke outcomes and the efficacy of experimental treatments in animal models. In the first sub‑project, a comprehensive search performed in July 2020 retrieved 6 406 unique records on metabolic diseases such as diabetes mellitus, obesity and metabolic syndrome. After title and abstract screening by two independent reviewers, 313 records were retained for full‑text assessment, and data from 188 independent studies were extracted. Preliminary analyses indicate that both diabetes and obesity worsen stroke outcomes in rodents, although the number of studies comparing metabolic‑syndrome models with healthy controls was insufficient to conduct a robust meta‑analysis. Likewise, neurobehavioural outcome data in obesity models were too sparse for quantitative synthesis. An updated search is underway to increase the evidence base for a forthcoming publication.
The second major review focused on arterial hypertension. The final search in October 2021 yielded 8 287 unique records. Following dual screening, 739 studies were selected for full‑text review, and 248 independent studies were ultimately included. Data extraction and analysis are currently in progress; the large sample size is expected to allow several quantitative effect measures to be calculated and reported in a future manuscript. The third review examined age and comorbidities in vitro. The team found that conventional title‑and‑abstract screening is less effective for in‑vitro studies, prompting the development of a more sensitive search strategy. Although no quantitative synthesis was completed, the work informs the design of future in‑vitro systematic reviews.
In parallel, the group developed a living evidence summary (SOLES) for preclinical in‑vivo focal cerebral ischaemia research. The protocol was published on OSF and the project presented at the European Stroke Journal and the European Stroke Organisation Conference. The living summary will continuously incorporate new studies, providing an up‑to‑date resource for researchers and clinicians.
All six protocols were published and registered on PROSPERO (CRD42020191339 for metabolic diseases, CRD42021283853 for hypertension), ensuring transparency and reducing duplication. Results have been presented at four international conferences, and a master’s thesis on obesity was completed with a grade of 1.1. The project’s data, including raw datasets exported from SyRF, will be deposited in OSF and accompanied by a data descriptor article; analysis code will be shared on GitHub to facilitate reproducibility.
Collaboration has been central to the project’s success. The core team includes senior investigators from RWTH Aachen University, Edinburgh University, and the University of Southern California, where Prof. Patrick Lyden of the Stroke Preclinical Assessment Network (SPAN) was consulted for potential joint initiatives. The project was funded through a German research grant (DFG), and the budget was carefully monitored; all personnel costs were utilised, while open‑access fees remain pending publication. The project timeline spanned from the initial search in 2020 to the latest data extraction in 2021, with ongoing updates and manuscript preparation. The collaborative framework enabled efficient division of labour, with students and post‑doctoral researchers handling screening, data extraction, and quality control, while senior scientists oversaw protocol development, statistical analysis, and dissemination. The project’s outcomes—robust systematic reviews, a living evidence summary, and open data resources—are poised to inform future preclinical stroke research and accelerate the translation of therapeutic strategies into clinical practice.
