{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T14:58:10Z","timestamp":1790261890351,"version":"4.1.0"},"reference-count":28,"publisher":"SAGE Publications","issue":"1_suppl","license":[{"start":{"date-parts":[[2017,9,1]],"date-time":"2017-09-01T00:00:00Z","timestamp":1504224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,9,1]],"date-time":"2017-09-01T00:00:00Z","timestamp":1504224000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurotrauma"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:p>\n                    Blast traumatic brain injury (bTBI) has been shown to contribute to progressive neurodegenerative disease. Recent evidence suggests that endoplasmic reticulum (ER) stress is a mechanistic link between acute neurotrauma and progressive tauopathy. We propose that ER stress contributes to extensive behavioral changes associated with a chronic traumatic encephalopathy (CTE)-like phenotype. Targeting ER stress is a promising option for the treatment of neurotrauma-related neurodegeneration, which warrants investigation. Utilizing our validated and clinically relevant Sprague\u2013Dawley blast model, we investigated a time course of mechanistic changes that occur following bTBI (50 psi) including: ER stress activation, iron-mediated toxicity, and tauopathy via Western blot and immunohistochemistry. These changes were associated with behavioral alterations measured by the Elevated Plus Maze (EPM), Forced Swim Test (FST), and Morris Water Maze (MWM). Following characterization, salubrinal, an ER stress modulator, was given at a concentration of 1\u2009mg\/kg post-blast, and its mechanism of action was determined\n                    <jats:italic toggle=\"yes\">in vitro.<\/jats:italic>\n                    bTBI significantly increased markers of injury in the cortex of the left hemisphere: p-PERK and p-eIF2\u03b1 at 30\u2009min, p-T205 tau at 6\u2009h, and iron at 24\u2009h. bTBI animals spent more time immobile on the FST at 72\u2009h and more time in the open arm of the EPM at 7 days. Further, bTBI caused a significant learning disruption measured with MWM at 21 days post-blast, with persistent tau changes. Salubrinal successfully reduced ER stress markers\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    while significantly improving performance on the EPM. bTBI causes robust biochemical changes that contribute to neurodegeneration, but these changes may be targeted with ER stress modulators.\n                  <\/jats:p>","DOI":"10.1089\/neu.2016.4680","type":"journal-article","created":{"date-parts":[[2017,1,11]],"date-time":"2017-01-11T23:06:44Z","timestamp":1484176004000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":36,"title":["Endoplasmic Reticulum Stress Modulation as a Target for Ameliorating Effects of Blast Induced Traumatic Brain Injury"],"prefix":"10.1177","volume":"34","author":[{"given":"Brandon P.","family":"Lucke-Wold","sequence":"first","affiliation":[{"name":"West Virginia University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aric F.","family":"Logsdon","sequence":"additional","affiliation":[{"name":"West Virginia University School of Pharmacy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan C.","family":"Turner","sequence":"additional","affiliation":[{"name":"West Virginia University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason D.","family":"Huber","sequence":"additional","affiliation":[{"name":"West Virginia University School of Pharmacy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles L.","family":"Rosen","sequence":"additional","affiliation":[{"name":"West Virginia University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2017,9,1]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nlw036"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)30057-6"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2016.00031"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0127971"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3171\/2016.1.FOCUS15607"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2015.11.007"},{"key":"e_1_3_3_8_2","first-page":"1","article-title":"Alzheimer's disease and chronic traumatic encephalopathy: Distinct but possibly overlapping disease entities","volume":"11","author":"Turner R.C.","year":"2016","unstructured":"Turner R.C., , Lucke\u2013Wold B.P., , Robson M.J., , Lee J.M., , and Bailes J.E. (2016). Alzheimer's disease and chronic traumatic encephalopathy: Distinct but possibly overlapping disease entities. Brain Inj. 11, 1\u201314.","journal-title":"Brain Inj"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.3171\/2015.3.JNS141802"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2015.08.005"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2013.07.008"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-014-8902-7"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2013.3102"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2014.00421"},{"key":"e_1_3_3_15_2","article-title":"Bryostatin-1 restores blood brain barrier integrity following blast-induced traumatic brain injury","author":"Lucke-Wold B.P.","year":"2014","unstructured":"Lucke-Wold B.P., , Logsdon A.F., , Smith K.E., , Turner R.C., , Alkon D.L., , Tan Z., , Naser Z.J., , Knotts C.M., , Huber J.D., , and Rosen C.L. (2014). Bryostatin-1 restores blood brain barrier integrity following blast-induced traumatic brain injury. Mol. Neurobiol.","journal-title":"Mol. Neurobiol"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.3171\/2012.8.JNS12358"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2011.08.021"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2016.04.063"},{"key":"e_1_3_3_19_2","article-title":"Neuropsychiatric symptom modeling in male and female C57BL\/6J mice after experimental traumatic brain injury","author":"Tucker L.B.","year":"2016","unstructured":"Tucker L.B., , Burke J.F., , Fu A.H., , and McCabe J.T. (2016). Neuropsychiatric symptom modeling in male and female C57BL\/6J mice after experimental traumatic brain injury. J Neurotrauma. [Epub ahead of print.]","journal-title":"J Neurotrauma."},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2011.1895"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2015.00222"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2015.4262"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2015.07.489"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2015.03.007"},{"key":"e_1_3_3_25_2","first-page":"e532","article-title":"Chronic traumatic encephalopathy: the impact on athletes","volume":"8","author":"Galgano M.A.","year":"2016","unstructured":"Galgano M.A., , Cantu R., and Chin L.S. (2016). Chronic traumatic encephalopathy: the impact on athletes. 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