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The potential of pharmacological interventionin experimental model of perinatal hypoxic ischemic insult

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The potential of pharmacological interventionin experimental model of perinatal hypoxic ischemic insult

Sonam Kapoor 1,2 David Kala 2 Jan Svodoba 2 Ivo Juranek 1 Zuzana Brnoliakova 1 Jakub Otahal 2

1Institute of Experimental Pharmacology and Toxicology, Centre of Experimental Medicine, Slovak Academy of Sciences, Bratislava, Slovak Republic
2Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic

Introduction Perinatal hypoxic ischemic (HI) insult represents a severe paediatric neurologic condition, where the incidence is about 1-4 per 1000 term births in the developed countries. Perinatal HI injury develops as the result of permanent irreversible brain damage in which surviving infants may suffer severe neurological and/or learning disorders. There are minimal diagnostic and limited therapeutic approaches, thus it’s a socio-economic burden. The goal of this work was to test, the potential of pharmacological intervention in prevention of brain damage in perinatal HI insult by using sulforaphane (SFN).

Method Seven days old Sprague-Dawley rats were utilized in animal model of HI injury. There were four groups of animals: HI and HI with SFN, Sham operated, Sham with SFN. SFN was administrated 5 mg/kg i.p., 24 h of occlusion. Common carotid artery occlusion was performed and ligated in anaesthetized pups’ animals and were incubated in a hypoxic chamber (pO2 8%) for 90 min. Measurments/quantification was done by PET imaging with 18F-FDG, applied i.p., after 1 day, 7 days and 5 weeks after the HI insult of the evaluation of glucose uptake after the HI insult with total activity ~12MBq in pups and ~18MBq in older animals. PMOD software and Schiffer rat brain MR atlas were used to analyze activities in individual brain regions.

Results Hippocampus and surrounding neocortex revealed significant changes in FDG bio-distribution. Most prominent changes were observed in hippocampus and cortex which means regions typically affected in this model of HI. Pretreatment with SFN led to protection of the hippocampus 1 day after the HI insult.

Conclusion Transcriptor factor Nrf2 and its activation with SFN represents promising treatment strategy in HI.

The project was supported by program QUALITAS of Strategy AV21 and grants no. 18-07908S CSF, 15-33115A AZV, APVV-18-0336 and VEGA 2/0166/20.
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