{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:58:21Z","timestamp":1790953101429,"version":"4.1.0"},"reference-count":73,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS127986"],"award-info":[{"award-number":["R01NS127986"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["66978"],"award-info":[{"award-number":["66978"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Advancement of Military Medicine","award":["R01NS127986"],"award-info":[{"award-number":["R01NS127986"]}]},{"name":"Advancement of Military Medicine","award":["66978"],"award-info":[{"award-number":["66978"]}]},{"name":"Neurosurgery Research and Education Foundation","award":["R01NS127986"],"award-info":[{"award-number":["R01NS127986"]}]},{"name":"Neurosurgery Research and Education Foundation","award":["66978"],"award-info":[{"award-number":["66978"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Brain ischemia causes disruption in cerebral blood flow and blood\u2013brain barrier integrity, which are normally maintained by astrocyte endfeet. Emerging evidence points to dysregulation of the astrocyte translatome during ischemia, but its effects on the endfoot translatome are unknown. In this study, we aimed to investigate the early effects of ischemia on the astrocyte endfoot translatome in a rodent cerebral ischemia and reperfusion model of stroke. To do so, we immunoprecipitated astrocyte-specific tagged ribosomes (RiboTag IP) from mechanically isolated brain microvessels. In mice subjected to middle cerebral artery occlusion and reperfusion and contralateral controls, we sequenced ribosome-bound RNAs from perivascular astrocyte endfeet and identified 205 genes that were differentially expressed in the endfoot translatome after ischemia. The main biological processes associated with these differentially expressed genes included proteostasis, inflammation, cell cycle\/death, and metabolism. Transcription factors whose targets were enriched amongst upregulated translating genes included HSF1, the master regulator of the heat shock response. The most highly upregulated genes in the translatome were HSF1-dependent Hspa1a and Hspa1b, which encode the inducible HSP70. Using qPCR, Western blot, and immunohistochemistry, we confirmed that HSP70 is upregulated in astrocyte endfeet after ischemia. This coincided with an increase in ubiquitination across the proteome that suggests that ischemia induces a disruption in proteostasis in astrocyte endfeet. These findings suggest a robust proteostasis response to proteotoxic stress in the endfoot translatome after ischemia. Modulating proteostasis in endfeet may be a strategy to preserve endfoot function and BBB integrity after ischemic stroke.<\/jats:p>","DOI":"10.3390\/ijms26010309","type":"journal-article","created":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T11:24:19Z","timestamp":1735730659000},"page":"309","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["RiboTag RNA Sequencing Identifies Local Translation of HSP70 in Astrocyte Endfeet After Cerebral Ischemia"],"prefix":"10.3390","volume":"26","author":[{"given":"Bosung","family":"Shim","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 20201, USA"},{"name":"Program in Molecular Medicine, University of Maryland School of Medicine, Baltimore, MD 20201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prajwal","family":"Ciryam","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 20201, USA"},{"name":"Shock Trauma Neurocritical Care, Program in Trauma, R Adams Cowley Shock Trauma Center, University of Maryland Medical Center, Baltimore, MD 20201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cigdem","family":"Tosun","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 20201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Serra","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 20201, USA"},{"name":"Program in Molecular Medicine, University of Maryland School of Medicine, Baltimore, MD 20201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalya","family":"Tsymbalyuk","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 20201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5097-1944","authenticated-orcid":false,"given":"Kaspar","family":"Keledjian","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 20201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6714-1946","authenticated-orcid":false,"given":"Volodymyr","family":"Gerzanich","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 20201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5373-1988","authenticated-orcid":false,"given":"J. Marc","family":"Simard","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 20201, USA"},{"name":"Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 20201, USA"},{"name":"Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 20201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e254","DOI":"10.1161\/CIR.0000000000000950","article-title":"Heart Disease and Stroke Statistics-2021 Update: A Report From the American Heart Association","volume":"143","author":"Virani","year":"2021","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e93","DOI":"10.1161\/CIR.0000000000001123","article-title":"Heart Disease and Stroke Statistics-2023 Update: A Report From the American Heart Association","volume":"147","author":"Tsao","year":"2023","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1001\/jama.2024.15563","article-title":"Leading Causes of Death in the US, 2019\u20132023","volume":"332","author":"Ahmad","year":"2024","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/S1474-4422(07)70055-8","article-title":"Brain oedema in focal ischaemia: Molecular pathophysiology and theoretical implications","volume":"6","author":"Simard","year":"2007","journal-title":"Lancet Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"799","DOI":"10.4103\/1673-5374.350699","article-title":"Acute and long-term changes in blood flow after ischemic stroke: Challenges and opportunities","volume":"18","author":"Premilovac","year":"2023","journal-title":"Neural Regen. 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