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

Glas, Michael; Frick, Tamara; Springe, Dirk; Putzu, Alessandro; Zürcher, Patrick; Grandgirard, Denis; Leib, Stephen; Jakob, Stephan; Takala, Jukka; Hänggi, Matthias (2018). Neuroprotection with the P53-Inhibitor Pifithrin-μ After Cardiac Arrest in a Rodent Model. Shock, 49(2), pp. 229-234. Lippincott Williams & Wilkins 10.1097/SHK.0000000000000917

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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 minutes 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 minutes cardiac arrest (8 minutes arrest pifithrin-μ 94 ± 47 vs control 128 ± 37; n = 11 each; 10 minutes 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > Clinic of Intensive Care
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases

UniBE Contributor:

Glas, Michael; Springe, Dirk; Zürcher, Patrick; Grandgirard, Denis; Leib, Stephen; Jakob, Stephan; Takala, Jukka and Hänggi, Matthias

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

1073-2322

Publisher:

Lippincott Williams & Wilkins

Language:

English

Submitter:

Mirella Aeberhard

Date Deposited:

10 Jul 2017 16:56

Last Modified:

01 Jun 2018 02:30

Publisher DOI:

10.1097/SHK.0000000000000917

PubMed ID:

28562478

BORIS DOI:

10.7892/boris.101339

URI:

https://boris.unibe.ch/id/eprint/101339

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