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Currently, there are no specific neuroprotective treatments available. Exendin-4 is a drug used for the treatment of type 2 diabetes mellitus, and it has shown neuroprotective effects in several neurological disorders including Alzheimer\u2019s and Parkinson\u2019s disease. In this study, we used the preterm postnatal day 5 rat model of GMH to evaluate whether exendin-4 exerts neuroprotective effects in this setting. Our results show that in the acute phase, exendin-4 reduced microglial activation, caspase-3 activation, p53 expression, AIF-associated cell death, MMP-9 expression, and neutrophil infiltration into the hemorrhage site. Exendin-4 treatment improved neurodevelopmental outcomes in both negative geotaxis and eye-opening latency when compared to saline-treated GMH controls, and conferred gray and white matter protection as early as 48\u2009h after injury, with persistent neuroprotection observed at 5, 11, and 35 days after GMH. Exendin-4-treated animals also showed significant recovery of motor function in the rotarod test. In summary, this study demonstrates that exendin-4 reduces brain injury in a rat model of GMH in both the short and long term and is associated with improved neurological outcome.<\/jats:p>","DOI":"10.1038\/s41419-026-09189-9","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T21:54:03Z","timestamp":1787176443000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exendin-4 improves neurodevelopmental outcome after neonatal germinal matrix hemorrhage"],"prefix":"10.1038","volume":"17","author":[{"given":"Andrea","family":"Jonsdotter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Lena","family":"Leverin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pernilla","family":"Svedin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Lindstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Ebefors","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1414-7279","authenticated-orcid":false,"given":"Ylva","family":"Carlsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Hagberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9342-4691","authenticated-orcid":false,"given":"Eridan","family":"Rocha-Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"9189_CR1","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1038\/s41582-020-00447-8","volume":"17","author":"P Ballabh","year":"2021","unstructured":"Ballabh P, de Vries LS. 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