{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:16:59Z","timestamp":1790713019768,"version":"4.1.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mechanical ventilation is a known risk factor for delirium, a cognitive impairment characterized by dysfunction of the frontal cortex and hippocampus. Although IL-6 is upregulated in mechanical ventilation\u2013induced lung injury (VILI) and may contribute to delirium, it is not known whether the inhibition of systemic IL-6 mitigates delirium-relevant neuropathology. To histologically define neuropathological effects of IL-6 inhibition in an experimental VILI model, VILI was simulated in anesthetized adult mice using a 35 cc\/kg tidal volume mechanical ventilation model. There were two control groups, as follow: 1) spontaneously breathing or 2) anesthetized and mechanically ventilated with 10 cc\/kg tidal volume to distinguish effects of anesthesia from VILI. Two hours before inducing VILI, mice were treated with either anti\u2013IL-6 antibody, anti\u2013IL-6 receptor antibody, or saline. Neuronal injury, stress, and inflammation were assessed using immunohistochemistry. CC3 (cleaved caspase-3), a neuronal apoptosis marker, was significantly increased in the frontal (P &amp;lt; 0.001) and hippocampal (P &amp;lt; 0.0001) brain regions and accompanied by significant increases in c-Fos and heat shock protein-90 in the frontal cortices of VILI mice compared with control mice (P &amp;lt; 0.001). These findings were not related to cerebral hypoxia, and there was no evidence of irreversible neuronal death. Frontal and hippocampal neuronal CC3 were significantly reduced with anti\u2013IL-6 antibody (P &amp;lt; 0.01 and P &amp;lt; 0.0001, respectively) and anti\u2013IL-6 receptor antibody (P &amp;lt; 0.05 and P &amp;lt; 0.0001, respectively) compared with saline VILI mice. In summary, VILI induces potentially reversible neuronal injury and inflammation in the frontal cortex and hippocampus, which is mitigated with systemic IL-6 inhibition. These data suggest a potentially novel neuroprotective role of systemic IL-6 inhibition that justifies further investigation.<\/jats:p>","DOI":"10.1165\/rcmb.2021-0072oc","type":"journal-article","created":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T14:19:41Z","timestamp":1621520381000},"page":"403-412","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":42,"title":["IL-6 Inhibition Reduces Neuronal Injury in a Murine Model of Ventilator-induced Lung Injury"],"prefix":"10.1093","volume":"65","author":[{"given":"Nicklaus A.","family":"Sparrow","sequence":"first","affiliation":[{"name":"Department of Neurology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faizan","family":"Anwar","sequence":"additional","affiliation":[{"name":"Department of Neurology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ambart E.","family":"Covarrubias","sequence":"additional","affiliation":[{"name":"Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Padmesh S.","family":"Rajput","sequence":"additional","affiliation":[{"name":"Department of Neurology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Harun","family":"Rashid","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peyton L.","family":"Nisson","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael M.","family":"Gezalian","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery"},{"name":"Department of Neurology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahed","family":"Toossi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery"},{"name":"Department of Neurology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maranatha O.","family":"Ayodele","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery"},{"name":"Department of Neurology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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