{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T16:53:04Z","timestamp":1788367984683,"version":"build-2803163510"},"reference-count":69,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS073584"],"award-info":[{"award-number":["NS073584"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS103433"],"award-info":[{"award-number":["NS103433"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS108529"],"award-info":[{"award-number":["NS108529"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Glia"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cellular stressors inhibit general protein synthesis while upregulating stress response transcripts and\/or proteins. Phosphorylation of the translation factor eIF2\u03b1 by one of the several stress\u2010activated kinases is a trigger for such signaling, known as the integrated stress response (ISR). The ISR regulates cell survival and function under stress. Here, germline knockout mice were used to determine contributions by three major ISR kinases, HRI\/EIF2AK1, GCN2\/EIF2AK4, and PKR\/\/EIF2AK2, to pathogenesis of moderate contusive spinal cord injury (SCI) at the thoracic T9 level. One\u2010day post\u2010injury (dpi), reduced levels of peIF2\u03b1 were found in\n                    <jats:italic>Hri<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    and\n                    <jats:italic>Gcn2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    , but not in\n                    <jats:italic>Pkr<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. In addition,\n                    <jats:italic>Hri<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice showed attenuated expression of the downstream ISR transcripts,\n                    <jats:italic>Atf4<\/jats:italic>\n                    or\n                    <jats:italic>Chop<\/jats:italic>\n                    . Such differential effects of SCI\u2010activated ISR correlated with a strong or moderate enhancement of locomotor recovery in\n                    <jats:italic>Hri<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    or\n                    <jats:italic>Gcn2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, respectively.\n                    <jats:italic>Hri<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice also showed reduced white matter loss, increased content of oligodendrocytes (OL) and attenuated neuroinflammation, including decreased lipid accumulation in microglia\/macrophages. Cultured neonatal\n                    <jats:italic>Hri<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    OLs showed lower ISR cytotoxicity. Moreover, cell autonomous reduction in neuroinflammatory potential was observed in microglia and bone marrow\u2010derived macrophages derived from\n                    <jats:italic>Hri<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. These data identify HRI as a major positive regulator of SCI\u2010associated secondary injury. In addition, targeting HRI may enable multimodal neuroprotection to enhance functional recovery after SCI.\n                  <\/jats:p>","DOI":"10.1002\/glia.24669","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T06:04:53Z","timestamp":1736143493000},"page":"1004-1021","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Reduced White Matter Damage and Lower Neuroinflammatory Potential of Microglia and Macrophages in\n                    <i>Hri\/Eif2ak1<\/i>\n                    <sup>\u2212\/\u2212<\/sup>\n                    Mice After Contusive Spinal Cord Injury"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4161-2516","authenticated-orcid":false,"given":"Sujata","family":"Saraswat Ohri","sequence":"first","affiliation":[{"name":"Kentucky Spinal Cord Injury Research Center University of Louisville, School of Medicine  Louisville Kentucky USA"},{"name":"Department of Neurological Surgery University of Louisville, School of Medicine  Louisville Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott A.","family":"Myers","sequence":"additional","affiliation":[{"name":"Kentucky Spinal Cord Injury Research Center University of Louisville, School of Medicine  Louisville Kentucky USA"},{"name":"Department of Neurological Surgery University of Louisville, School of Medicine  Louisville Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Rood","sequence":"additional","affiliation":[{"name":"Kentucky Spinal Cord Injury Research Center University of Louisville, School of Medicine  Louisville Kentucky USA"},{"name":"Department of Biochemistry &amp; Molecular Genetics University of Louisville, School of Medicine  Louisville Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon L.","family":"Brown","sequence":"additional","affiliation":[{"name":"Kentucky Spinal Cord Injury Research Center University of Louisville, School of Medicine  Louisville Kentucky USA"},{"name":"Department of Anatomical Sciences &amp; Neurobiology University of Louisville, School of Medicine  Louisville Kentucky USA"},{"name":"Department of Pharmacology &amp; Toxicology University of Louisville, School of Medicine  Louisville Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula M.","family":"Chilton","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition University of Louisville, School of Medicine  Louisville Kentucky USA"},{"name":"Norton Neuroscience Institute  Louisville Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukasz","family":"Slomnicki","sequence":"additional","affiliation":[{"name":"Kentucky Spinal Cord Injury Research Center University of Louisville, School of Medicine  Louisville Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"Kentucky Spinal Cord Injury Research Center University of Louisville, School of Medicine  Louisville Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George Z.","family":"Wei","sequence":"additional","affiliation":[{"name":"Kentucky Spinal Cord Injury Research Center University of Louisville, School of Medicine  Louisville Kentucky USA"},{"name":"Department of Interdisciplinary Program in Translational Neuroscience University of Louisville, School of Medicine  Louisville Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kariena R.","family":"Andres","sequence":"additional","affiliation":[{"name":"Kentucky Spinal Cord Injury Research Center University of Louisville, School of Medicine  Louisville Kentucky USA"},{"name":"Department of Neurological Surgery University of Louisville, School of Medicine  Louisville Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divya","family":"Mohan","sequence":"additional","affiliation":[{"name":"Kentucky Spinal Cord Injury Research Center University of Louisville, School of Medicine  Louisville Kentucky USA"},{"name":"Department of Neurological Surgery University of Louisville, School of Medicine  Louisville Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell M.","family":"Howard","sequence":"additional","affiliation":[{"name":"Kentucky Spinal Cord Injury Research Center University of Louisville, School of Medicine  Louisville Kentucky USA"},{"name":"Department of Neurological Surgery University of Louisville, School of Medicine  Louisville Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott R.","family":"Whittemore","sequence":"additional","affiliation":[{"name":"Kentucky Spinal Cord Injury Research 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