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Sep 12, 2018

ERC congress - Resuscitation 2018

5 - Crosstalk between endoplasmic reticulum stress, cytokines and neuroinflammatory biomarkers as a putative panel of biomarkers for neurological outcome prognostication after cardiac arrest and resuscitation.







Post cardiac arrest syndrome (PCAS) yet contributes to unfavorable neurological and cardiac outcome even with successful resuscitation. However, the exact mechanism is yet to be elucidated. Purpose of the study; This study investigated the level of expression endoplasmic reticulum (ER) stress downstream biomarkers; Inositol Requiring 1 (IRE1), PKR-like ER kinase (PERK), Activating Transcription Factor 4 and 6 (ATF4 and ATF6), Immunoglobulin-heavy-chain binding protein (BiP), spliced form of X-box binding protein (XBP1), glucose-regulated protein78 (GRP78) and caspase-3 after cardiac arrest (CA) and resuscitation and their correlation with Inflammatory biomarkers; interleukin (IL)-6, IL-10 and Tumor Necrosis Factor-α (TNF-α)) and neuroinflammatory biomarkers; neurogranin (NRGN), neuron specific enolase (NSE), metallothionein 3(MT3) and S100B as a prognostic value of neurological outcome. Materials and Methods: Sprague Dawley rats were subjected to 5 min electrically induced CA followed by standard resuscitation. Animals were decapitated at 6, 12, 24h and 48h (n=6 per group) after return of spontaneous circulation (ROSC). Frontal motor and cerebellar cortex were biochemically assessed for inflammatory cytokines and neuroinflammatory biomarkers, analyzed using reverse transcription polymerase chain reaction for transcriptional profile and evaluated for histological, ultrastructural and immunohistochemical changes. Results: The mRNA levels of PERK, ATF4 and GRP78 were significantly elevated in 6-48 hr after ROSC as well as the associated caspase-3 apoptic transcription. Typical apoptotic nuclei were obviously displayed in frontal cortex and cerebellum 24h after resuscitation. Further, a significant increase in integrated density for PERK immunostaining and number of apoptosis caspase-3 positive cells/HPF were detected. All inflammatory biomarkers were correlated positively with the upregulated levels of ER stress biomarkers. Conclusions: ER stress-mediated apoptosis, cytokines and neuroinflammatory biomarkers could serve as main prognostication panel for outcome after cardiac arrest and resuscitation.

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© Copyright 2019 Morressier GmbH.
All rights reserved.