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Article History

Received: 13 May 2025

Accepted: 23 July 2025

First Online: 15 October 2025

Acknowledgements

: We thank F. Bahram (Department of Clinical Science and Education, Karolinska Institutet, Stockholm, Sweden) for technical assistance, and H. Pettersson (Department of Clinical Science and Education, Karolinska Institutet, Stockholm, Sweden) for advice on statistical analyses.

: The data that support the findings of this study are not openly available for reasons of sensitivity, but are available from the corresponding author upon reasonable request. Data are located in controlled-access data storage (data repository) at the Karolinska Institutet.

: Open access funding provided by Karolinska Institute. Funding was provided by the Swedish Medical Research Council (to CP), the FANG Foundation and the Swedish Brain Foundation (to CP), the Swedish Heart–Lung Foundation (to TN), the Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse (to TN), the Ulla Hamberg Angeby och Lennart Angebys Stiftelse (to VD and EV), the Swedish Stroke Foundation (to CP, VD and EV), the Foundation for Geriatric Diseases at Karolinska Institutet (to EV), ALF Stockholm (to TN) and by a grant from Boehringer Ingelheim Pharma GmbH & Co. KG.

: TN has received consultancy fees from Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Merck and Sanofi. TK, PH and KB are employed at Boehringer Ingelheim Pharma GmbH & Co. KG. The remaining authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.

: EV substantially contributed to the design of the work, performed part of the drug administration and diabetic tests in studies 1–3, and part of the immunohistochemical and stereology analysis. Moreover, she drafted and critically reviewed the article with DK, and approved the final version of the manuscript. DK substantially contributed to the design of the work, performed part of the drug administration and diabetic tests in studies 1 and 3 and part of the immunohistochemical and stereology analysis, and acquired/processed images. Moreover, she drafted and critically reviewed the article with EV, and approved the final version of the manuscript. MN performed part of the immunohistochemical studies and reviewed the article critically. MOR provided resources and contributed to the conception of the work. She also reviewed the manuscript. TN contributed to the conception of the study, provided resources, and critically revised the manuscript. PH synthesised the BI8271 compound and substantially contributed to the analysis and interpretation of data and critically reviewed the article. KB provided the data used to determine the doses of the compounds, contributed to the analysis and interpretation of data and critically reviewed the article. TK conceived the study and provided resources, including semaglutide/BI8271, and revised the manuscript. VD conceived and designed the study, performed the stroke experiments and part of the diabetic/functional tests, and edited the manuscript. CP conceived, designed and coordinated the research plan, and wrote the manuscript. All authors approved the final version to be published. EV, VD and CP are responsible for the integrity of the work as a whole.