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309 Tumor Necrosis Factor-Inducible Gene 6 Protein: A Novel Neuroprotective Factor Against Inflammatory Developmental Brain Injury
  1. F Bertling1,
  2. S Prager1,
  3. R Hermann1,
  4. I Bendix1,
  5. HG Wisniewski2,
  6. U FelderhoffMüser1,
  7. M Keller3
  1. 1Dept. of Paediatrics I - Neonatology, University Hospital Essen, Essen, Germany
  2. 2Dept. of Microbiology, NYU School of Medicine, New York, NY, USA
  3. 3Children’s Hospital Passau, Passau, Germany

Abstract

Background and Aims An important factor of developmental brain injury is inflammation. It has been shown that tumor necrosis factor-inducible gene 6 protein (TSG-6) has anti-inflammatory effects in several inflammatory conditions. Nothing is known so far about the role of TSG-6 in the developing brain, its impact on inflammation and its therapeutic potential.

Methods PCR, Western Blotting and Immunohistochemistry was performed according to standard protocols. Brain hemispheres of untreated Wistar rats (p1-p15) were evaluated under developmental aspects of TSG-6. LPS-treated rats (0.25mg/kg LPS i.p. on p3) were evaluated under pathological aspects of TSG-6. To evaluate whether exogenous rhTSG-6 reduces inflammatory-induced brain injury, newborn Wistar rats, exposed to LPS at p3, were treated with rhTSG-6 i.p. (four repetitive doses of 2.25mg/kg every 12h, first dose three hours before LPS-injection).

Results Investigations of TSG-6’s developmental brain expression showed a linear increase from p1 to p15 on gene level. Additionally, different expression was detected in Cortex, Thalamus and Striatum on gene level at p6. Expression of TSG-6 after LPS treatment (0–24h) was significantly increased on gene level and tendentiously on protein level. cCaspase-3, a marker of apoptosis, showed a significant down-regulation of >30% under additional TSG-6 treatment versus sole LPS exposure (n=12–14, p=0,025).

Conclusions TSG-6 Expression is developmentally regulated and increased after LPS exposure. The reduction of activated Caspase-3 demonstrates the neuroprotective potential of exogenous TSG-6 administration in inflammatory-induced developmental brain injury.

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