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PS-336 Influence Of N-acetylcysteine Amide (naca) On The Inflammasome Pathway. A Study On Neonatal Pigs
  1. T Benterud1,
  2. M Ystgard1,
  3. L Pankratov1,
  4. S Norgren2,
  5. R Solberg1,
  6. OD Saugstad1
  1. 1Department of Pediatric Research, Oslo University Hospital, Oslo, Norway
  2. 2Department of Pediatric Medicine, Karolinska University Hospital, Stockholm, Sweden

Abstract

Background and aims Severe perinatal hypoxia contributes to approximately 6% of spastic cerebral palsy (CP). Studies have indicated an association between elevation of IL-1beta after perinatal asphyxia and the development of CP. The NLRP3 Inflammasome complex may lead to release of the cytokines IL-1beta and IL-18 and cell death. Reactive oxygen species (ROS) have been proposed to be an upstream inducer of this complex and the anti-oxidant N-Acetylcysteine amide (NACA) may provide organ protection after hypoxia.

Objectives To map inflammasome activation in specific brain regions of the pig after neonatal hypoxia-reoxygenation and to investigate if the expression of different proteins in this pathway are modulated by NACA.

Study design (Table 1).

ELISA was used to measure IL-1b protein in cerebral cortex and Realtime PCR for mRNA expression of NLRP3, ASC, IL-1b and Il18 in cortex, cerebellum, hippocampus and striatum.

Abstract PS-336 Table 1

Study design: Fifty-four newborn piglets, age 1236h, were included. Invasive blood pressure, EEG and ECG were measured continuously. One control group (n = 6) and 4 experimental groups (n = 12), exposed to global hypoxia, until BE was either -15 or -20 mmol/l (moderate/severe asphyxia with or without NACA) The pigs were observed for 9.5 h

Results After severe hypoxia the protein expression of IL-1b in cerebral cortex was reduced for the NACA treated pigs vs. saline, p < 0.05.

When comparing all the pigs treated with NACA vs. saline after hypoxia Fold Change of ASC in cortex was significantly reduced, p (Table 2 ).

Abstract PS-336 Table 2

Fold change for NLRP3, ASC, IL-18 and IL-1b measured in cerebral cortex. Significant difference in Fold Change of ASC (*), p < 0.05. All values are Median values

In hippocampus, cortex and Striatum Fold Change of IL-1b was elevated in all the hypoxia groups compared with the control group, p

Conclusion NACA reduces the protein expression of Il-1beta and mRNA-expression of ASC in cortex after hypoxia. This may indicate that NACA has some neuroprotective abilities after perinatal asphyxia.

Upcoming analyses of histopathology and injury markers will elucidate possible neuroprotective effects of NACA treatment following birth asphyxia.

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