PhD Scientific Days 2020

Theoretical and Translational III. Lectures

Multi-organ Damage Following Perinatal Asphyxia in Rat Model

Előadó neve

Lakat, Tamás

Előadó munkahelye

Semmelweis University; 1st Department of Pediatrics

Előadó telefonszáma

+36702619650

Előadó e-mail címe

tamas.lakat@gmail.com

Az előadás címe

Multi-organ Damage Following Perinatal Asphyxia in Rat Model

Szerző(k) neve és munkahelye

T. Lakat1,2; A. Hosszu1,2; A. Molnar1; A. R. Toth1; K. Demeter6; H. Kelemen2,3; E Mikics3; A. J. Szabo2,4; A. Dénes5; A. Fekete1,2

1MTA-SE “Lendület” Diabetes Research Group, Budapest, Hungary
2Semmelweis University 1st Department of Pediatrics, Budapest, Hungary
3Laboratory of Translational Behavioural Neuroscience, Institute of Experimental Medicine, Budapest, Hungary
4MTA-SE Pediatrics and Nephrology Research Group, Budapest, Hungary
5Laboratory of Neuroimmunology, Institute of Experimental Medicine, Budapest, Hungary
6Behavioral Studies Unit, Institute of Experimental Medicine, Budapest, Hungary

Szekció

Theoretical and Translational III. Lectures

Language of the presentation

English

Section, first choice

Molecular Sciences

Section, second choice

Theoretical and Translational Medicine

Összefoglaló szövege

Introduction
Perinatal asphyxia (PA) leads to death of more than half million mature newborns yearly. PA is associated with several serious complications including hypoxic encephalopathy, renal- hepatic- and cardiovascular injury, as well as respiratory distress. Basic research and clinical trials mainly focus on mitigating central nervous system damage by selective head or whole-body cooling. However, the extent of PA-associated multi-organ damage is not clarified yet and effective therapies are lacking.
Aims:
The aim of the present study was to determine acute renal, hepatic and cardiac damage after PA and to identify pathways involved in the pathomechanism.
Methods:
Postnatal 7 day-old male Wistar rat pups (n=5-10/group) were randomly grouped as follows: (i) Baseline: sacrificed immediately (ii) Control: pups were separated from the dam and incubated in normal air; (iii) PA: pups were separated and incubated in 4% O2; 20% CO2 in N2 gas mixture for 15 minutes. Samples were collected after 4 (T4) and 24 (T24) hours. Serum levels of electrolytes, kidney and liver functional parameters and Troponin I were determined. Sensitive tubular injury markers Kim1 and Ngal were measured. Expressions of hypoxic (Hif1a, Hif2a), inflammatory (Il1α, Il1β, Il6, Tnfα), apoptotic (Bax, Bcl-2) and angiogenic genes (Vegf, Epo) and heat shock proteins (Hsp27, Hsp72) were investigated. Periodic-Acid Schiff and anti-CD45 staining on kidney, and Hematoxylin&Eosin staining on liver sections were performed.
Results:
Blood urea nitrogen (BUN) and serum GPT were elevated at T4 following PA. Kim1, Ngal and heat shock protein expressions were increased, inflammatory and angiogenic pathways were activated in the kidney after PA. Vacuolisation, cytoplasmic degradation, and the onset of necrosis were observed in the liver following PA. In the liver hypoxic and apoptotic pathways were activated at T24 in the PA and in the control group. Serum Troponin I was elevated after PA indicating myocardial damage. Inflammatory cytokine and heat shock protein expression increased in the heart as well.
Conclusion:
Acute renal, hepatic and myocardial damage was observed after PA. These results may justify the need for clinical follow-up and novel treatment strategies for possible multi-organ damage. The molecular pathways described here are potential targets for therapeutic intervention.

Additional Information

Supervisor: Andrea Fekete
E-mail address: andrea.drfekete@gmail.com

Grants: NN OTKA-114607, VKE-2017-00006, FK124491

Bemutatás módja

Szóbeli

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4763

Start

10:55

End

11:10

Authors (legacy)

T. Lakat1,2; A. Hosszu1,2; A. Molnar1; A. R. Toth1; K. Demeter6; H. Kelemen2,3; E Mikics3; A. J. Szabo2,4; A. Dénes5; A. Fekete1,2

1MTA-SE “Lendület” Diabetes Research Group, Budapest, Hungary
2Semmelweis University 1st Department of Pediatrics, Budapest, Hungary
3Laboratory of Translational Behavioural Neuroscience, Institute of Experimental Medicine, Budapest, Hungary
4MTA-SE Pediatrics and Nephrology Research Group, Budapest, Hungary
5Laboratory of Neuroimmunology, Institute of Experimental Medicine, Budapest, Hungary
6Behavioral Studies Unit, Institute of Experimental Medicine, Budapest, Hungary