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Neuroprotection with the P53-Inhibitor Pifithrin-μ after Cardiac Arrest in a Rodent Model

Glas, Michael; Frick, Tamara; Springe, Dirk; Putzu, Alessandro; Zuercher, Patrick; Grandgirard, Denis; Leib, Stephen L; Jakob, Stephan M; Takala, Jukka; Haenggi, Matthias (2018). Neuroprotection with the P53-Inhibitor Pifithrin-μ after Cardiac Arrest in a Rodent Model. Shock, 49(2):229-234.

Abstract

BACKGROUND The small molecule pifithrin-μ reversibility inhibits the mitochondrial pathway of apoptosis. The neuronal effects of pifithrin-μ applied after cardiac arrest are unknown. We hypothesized that pifithrin-μ reduces neuronal damage in the most vulnerable brain region, the hippocampus, after cardiac arrest. METHODS In two randomized controlled series we administered pifithrin-μ or control in 109 rats resuscitated after 8 or 10 min of cardiac arrest. Neuronal damage was blindly assessed with histology (Fluoro Jade B: FJB, cresyl violet: CV) in the most vulnerable brain region (CA1 segment of hippocampus) and with a series of neurobehavioral tests (Open Field Task, Tape-Removal Test, Morris Water Maze test). Mixed ANOVA was used to combine both series, simple comparisons were done with t tests or Mann-Whitney U test. RESULTS Pifithrin-μ reduced the number of degenerating, FJB-positive neurons by 25% (mixed ANOVA p group = 0.014). This was more prominent after 8 min cardiac arrest (8 min arrest pifithrin-μ 94 ± 47 vs control 128 ± 37; n = 11 each; 10 min arrest pifithrin-μ 78 ± 44, n = 15 vs control 101 ± 31, n = 18; p group* arrest length interaction = 0.622). The reduction of ischemic CV-positive neurons in pifithrin-μ animals was not significant (ANOVA p group = 0.063). No significant group differences were found in neurobehavioral testing. CONCLUSION Temporarily inhibition of apoptosis with pifithrin-μ after cardiac arrest decreases the number of injured neurons in the CA1 segment of hippocampus in a cardiac arrest rat model, without clinical correlate. Further studies should elucidate the role of this neuroprotective agent in different settings and with longer cardiac arrest.

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Cardiocentro Ticino
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Emergency Medicine
Health Sciences > Critical Care and Intensive Care Medicine
Uncontrolled Keywords:Critical Care and Intensive Care Medicine, Emergency Medicine
Language:English
Date:February 2018
Deposited On:07 Feb 2018 16:30
Last Modified:18 Oct 2024 01:36
Publisher:Lippincott Williams & Wilkins
ISSN:1073-2322
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1097/SHK.0000000000000917
PubMed ID:28562478
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