Dissertation/Thesis
Προβολή σε EDS

Gasdermin-D Genetic Knockout Reduces Inflammasome-Induced Disruption of the Gut-Brain Axis After Traumatic Brain Injury

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Gasdermin-D Genetic Knockout Reduces Inflammasome-Induced Disruption of the Gut-Brain Axis After Traumatic Brain Injury
Συγγραφείς: Erika d. l. R. M. Cabrera Ranaldi, Helen M. Bramlett, Oliver Umland, Leo I. Levine, Robert W. Keane, Juan Pablo de Rivero Vaccari, W. Dalton Dietrich, Nadine A. Kerr
Πηγή: International Journal of Molecular Sciences ; Volume 26 ; Issue 8 ; Pages: 3512
Στοιχεία εκδότη: Multidisciplinary Digital Publishing Institute
Έτος έκδοσης: 2025
Συλλογή: MDPI Open Access Publishing
Θεματικοί όροι: inflammasome, pyroptosis, interleukin, IL-1β, traumatic brain injury, exosomes, extracellular vesicles, gut dysfunction
Περιγραφή: Traumatic brain injury (TBI) pathology is significantly mediated by an inflammatory response involving inflammasome activation, resulting in the release of interleukin (IL)-1β and pyroptotic cell death through gasdermin-D (GSDMD) cleavage. Inflammasome components are transported through extracellular vesicles (EVs) to mediate systemic inflammation in peripheral organs, including the gut. The purpose of this study was to determine the protective effect of GSDMD knockout (KO) on TBI-induced inflammasome activation, EV signaling, and gut function. GSDMD-KO and C57BL6 (WT) mice were subjected to the controlled cortical impact model of TBI. Cytokine expression was assessed with electrochemiluminescent immunoassay and immunoblotting of the cerebral cortex and gut. EVs were examined for pathology-associated markers using flow cytometry, and gut permeability was determined. GSDMD-KO attenuated IL-1β and IL-6 expression in the cerebral cortex and reduced IL-1β and IL-18 in the gut 3 days post-injury. GSDMD-KO mice had decreased neuronal- and gut-derived EVs compared to WT mice post-TBI. GSDMD-KO EVs also had decreased IL-1β and different surface marker expression post-TBI. GSDMD-KO mice had decreased gut permeability after TBI. These data demonstrate that GSDMD ablation improves post-TBI inflammation and gut pathology, suggesting that GSDMD may serve as a potential therapeutic target for the improvement of TBI-associated pathologies.
Τύπος εγγράφου: Thesis
Περιγραφή αρχείου: application/pdf
Γλώσσα: English
Relation: Molecular Biology; https://dx.doi.org/10.3390/ijms26083512
DOI: 10.3390/ijms26083512
Διαθεσιμότητα: https://doi.org/10.3390/ijms26083512
Rights: https://creativecommons.org/licenses/by/4.0/
Αριθμός Καταχώρησης: edsbas.F7D9AA80
Βάση Δεδομένων: BASE
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  – Url: https://doi.org/10.3390/ijms26083512#
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  Data: Gasdermin-D Genetic Knockout Reduces Inflammasome-Induced Disruption of the Gut-Brain Axis After Traumatic Brain Injury
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  Data: <searchLink fieldCode="AR" term="%22Erika+d%2E+l%2E+R%2E+M%2E+Cabrera+Ranaldi%22">Erika d. l. R. M. Cabrera Ranaldi</searchLink><br /><searchLink fieldCode="AR" term="%22Helen+M%2E+Bramlett%22">Helen M. Bramlett</searchLink><br /><searchLink fieldCode="AR" term="%22Oliver+Umland%22">Oliver Umland</searchLink><br /><searchLink fieldCode="AR" term="%22Leo+I%2E+Levine%22">Leo I. Levine</searchLink><br /><searchLink fieldCode="AR" term="%22Robert+W%2E+Keane%22">Robert W. Keane</searchLink><br /><searchLink fieldCode="AR" term="%22Juan+Pablo+de+Rivero+Vaccari%22">Juan Pablo de Rivero Vaccari</searchLink><br /><searchLink fieldCode="AR" term="%22W%2E+Dalton+Dietrich%22">W. Dalton Dietrich</searchLink><br /><searchLink fieldCode="AR" term="%22Nadine+A%2E+Kerr%22">Nadine A. Kerr</searchLink>
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  Data: International Journal of Molecular Sciences ; Volume 26 ; Issue 8 ; Pages: 3512
– Name: Publisher
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  Data: Multidisciplinary Digital Publishing Institute
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  Data: 2025
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  Data: MDPI Open Access Publishing
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  Data: <searchLink fieldCode="DE" term="%22inflammasome%22">inflammasome</searchLink><br /><searchLink fieldCode="DE" term="%22pyroptosis%22">pyroptosis</searchLink><br /><searchLink fieldCode="DE" term="%22interleukin%22">interleukin</searchLink><br /><searchLink fieldCode="DE" term="%22IL-1β%22">IL-1β</searchLink><br /><searchLink fieldCode="DE" term="%22traumatic+brain+injury%22">traumatic brain injury</searchLink><br /><searchLink fieldCode="DE" term="%22exosomes%22">exosomes</searchLink><br /><searchLink fieldCode="DE" term="%22extracellular+vesicles%22">extracellular vesicles</searchLink><br /><searchLink fieldCode="DE" term="%22gut+dysfunction%22">gut dysfunction</searchLink>
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  Data: Traumatic brain injury (TBI) pathology is significantly mediated by an inflammatory response involving inflammasome activation, resulting in the release of interleukin (IL)-1β and pyroptotic cell death through gasdermin-D (GSDMD) cleavage. Inflammasome components are transported through extracellular vesicles (EVs) to mediate systemic inflammation in peripheral organs, including the gut. The purpose of this study was to determine the protective effect of GSDMD knockout (KO) on TBI-induced inflammasome activation, EV signaling, and gut function. GSDMD-KO and C57BL6 (WT) mice were subjected to the controlled cortical impact model of TBI. Cytokine expression was assessed with electrochemiluminescent immunoassay and immunoblotting of the cerebral cortex and gut. EVs were examined for pathology-associated markers using flow cytometry, and gut permeability was determined. GSDMD-KO attenuated IL-1β and IL-6 expression in the cerebral cortex and reduced IL-1β and IL-18 in the gut 3 days post-injury. GSDMD-KO mice had decreased neuronal- and gut-derived EVs compared to WT mice post-TBI. GSDMD-KO EVs also had decreased IL-1β and different surface marker expression post-TBI. GSDMD-KO mice had decreased gut permeability after TBI. These data demonstrate that GSDMD ablation improves post-TBI inflammation and gut pathology, suggesting that GSDMD may serve as a potential therapeutic target for the improvement of TBI-associated pathologies.
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  Data: Molecular Biology; https://dx.doi.org/10.3390/ijms26083512
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        Value: 10.3390/ijms26083512
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      – Text: English
    Subjects:
      – SubjectFull: inflammasome
        Type: general
      – SubjectFull: pyroptosis
        Type: general
      – SubjectFull: interleukin
        Type: general
      – SubjectFull: IL-1β
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      – SubjectFull: traumatic brain injury
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      – SubjectFull: exosomes
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      – SubjectFull: extracellular vesicles
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      – SubjectFull: gut dysfunction
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      – TitleFull: Gasdermin-D Genetic Knockout Reduces Inflammasome-Induced Disruption of the Gut-Brain Axis After Traumatic Brain Injury
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            – TitleFull: International Journal of Molecular Sciences ; Volume 26 ; Issue 8 ; Pages: 3512
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