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Systemic interleukin-6 inhibition ameliorates acute neuropsychiatric phenotypes in a murine model of acute lung injury.
Anwar, Faizan; Sparrow, Nicklaus A; Rashid, Mohammad Harun; Guidry, Gena; Gezalian, Michael M; Ley, Eric J; Koronyo-Hamaoui, Maya; Danovitch, Itai; Ely, E Wesley; Karumanchi, S Ananth; Lahiri, Shouri.
  • Anwar F; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Sparrow NA; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Rashid MH; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Guidry G; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Gezalian MM; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Ley EJ; Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Koronyo-Hamaoui M; Division of Trauma and Critical Care, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Danovitch I; Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Ely EW; Division of Applied Cell Biology and Physiology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Karumanchi SA; Department of Psychiatry and Behavioral Neurosciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Lahiri S; Critical Illness, Brain Dysfunction, Department of Pulmonary and Critical Care Medicine, Survivorship (CIBS) Center, Veteran's Affairs Tennessee Valley Geriatric Research Education and Clinical Center (GRECC), Vanderbilt University School of Medicine, Nashville, TN, USA.
Crit Care ; 26(1): 274, 2022 09 13.
Article in English | MEDLINE | ID: covidwho-2038848
ABSTRACT
Acute neuropsychiatric impairments occur in over 70% of patients with acute lung injury. Mechanical ventilation is a well-known precipitant of acute lung injury and is strongly associated with the development of acute delirium and anxiety phenotypes. In prior studies, we demonstrated that IL-6 mediates neuropathological changes in the frontal cortex and hippocampus of animals with mechanical ventilation-induced brain injury; however, the effect of systemic IL-6 inhibition on structural and functional acute neuropsychiatric phenotypes is not known. We hypothesized that a murine model of mechanical ventilation-induced acute lung injury (VILI) would induce neural injury to the amygdala and hippocampus, brain regions that are implicated in diverse neuropsychiatric conditions, and corresponding delirium- and anxiety-like functional impairments. Furthermore, we hypothesized that these structural and functional changes would reverse with systemic IL-6 inhibition. VILI was induced using high tidal volume (35 cc/kg) mechanical ventilation. Cleaved caspase-3 (CC3) expression was quantified as a neural injury marker and found to be significantly increased in the VILI group compared to spontaneously breathing or anesthetized and mechanically ventilated mice with 10 cc/kg tidal volume. VILI mice treated with systemic IL-6 inhibition had significantly reduced amygdalar and hippocampal CC3 expression compared to saline-treated animals and demonstrated amelioration in acute neuropsychiatric behaviors in open field, elevated plus maze, and Y-maze tests. Overall, these data provide evidence of a pathogenic role of systemic IL-6 in mediating structural and functional acute neuropsychiatric symptoms in VILI and provide preclinical justification to assess IL-6 inhibition as a potential intervention to ameliorate acute neuropsychiatric phenotypes following VILI.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Delirium / Acute Lung Injury / Ventilator-Induced Lung Injury Topics: Long Covid Limits: Animals Language: English Journal: Crit Care Year: 2022 Document Type: Article Affiliation country: S13054-022-04159-x

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Delirium / Acute Lung Injury / Ventilator-Induced Lung Injury Topics: Long Covid Limits: Animals Language: English Journal: Crit Care Year: 2022 Document Type: Article Affiliation country: S13054-022-04159-x