10 - Comparing the potency of different neuroprotective agents following neonatal hypoxic-ischemic brain injury in newborn rats – a multi-drug randomized controlled screening trial

Monday, May 1, 2023

9:30 AM – 11:30 AM ET

Poster Number: 10
Publication Number: 10.433

Hemmen Sabir, University Hospital Bonn, Bonn, Nordrhein-Westfalen, Germany; Maria E. Bernis, Eltern Kind Zentrum Uniklinikum Bonn, Bonn, Nordrhein-Westfalen, Germany; Margit Zweyer, DZNE, Bonn, Nordrhein-Westfalen, Germany; Elke Maes, UKB, Bonn, Nordrhein-Westfalen, Germany

Presenting Author(s)

HS

Hemmen Sabir, MD (he/him/his)

Consultant
University Hospital Bonn
Bonn, Nordrhein-Westfalen, Germany

Background: Intrapartum hypoxia-ischaemia leading to neonatal encephalopathy (NE) results in significant neonatal mortality and morbidity worldwide, with >85% of cases in low and middle income countries (LMIC). Therapeutic hypothermia (HT) is currently the only available safe and effective treatment of HIE in high income countries (HIC), however has not shown safety or efficacy in LMIC. Other therapies are urgently needed.

Objective: Our aim was to compare treatment effects of putative neuroprotective drug candidates following neonatal hypoxic-ischemic (HI) brain injury in an established P7 rat Vannucci model.

Design/Methods: We conducted the first multi-drug randomized-controlled preclinical screening trial, investigating 26 potential therapeutic agents using a standardized experimental setting where P7 rat pups were exposed to unilateral HI brain injury. Brains were analysed for unilateral brain area loss following 7d survival.

Results: In total, 20 animal experiments were performed. Eight of the 26 therapeutic agents significantly reduced brain area loss with the strongest treatment effect for Caffeine, Sonic Hedgehog Agonist (SAG) and Allopurinol, followed by Melatonin, Clemastine, ß-Hydroxybutyrate, Omegaven, and Iodide. The probability of efficacy was superior to HT for Caffeine, SAG, Allopurinol, Melatonin, Clemastine, ß-Hydroxybutyrate, and Omegaven.

Conclusion(s):

We provide the results of the first systematic preclinical screen of potential neuroprotective treatments and present alternative single therapies that may be promising treatment options to HT in LMIC.