Abstracto

No effectiveness of synthetic anti-inflammatory tetrapeptides in a mouse model of ischemic stroke

Heleen M den Hertog, Karen Gertz, Wim A Dik, Dirk J Duncker, Nisar A Khan, Matthias Endres, Robbert Benner and Peter J Koudstaal

Background. Inflammation plays an important role in the pathophysiology of ischemic stroke and may contri-bute to secondary damage following ischemic stroke. Recently, it has been shown that synthetic oligopeptides related to human chorionic gonadotropin (hCG) and various other synthetic oligopeptides may have immuno-modulatory effects.
We aimed to investigate the effects of two promising synthetic anti-inflammatory tetrapeptides, namely the hCG-related peptide AQGV and the p53-related peptide EPPE on infarct volume and on inflammatory gene expres-sion in a mouse model of focal cerebral ischemia.

Methods. In a randomized single-blinded fashion, mice received two intravenous injections of either AQGV (30 mg/kg bodyweight) or EPPE (30mg/kg bodyweight) or phosphate buffered saline. The first dose was adminis-tered directly before 90-minutes middle cerebral artery occlusion, and the second dose was injected directly af-ter reperfusion. Infarct volume and gene expression levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), E-selectin and intercellular adhesion molecule-I (ICAM-1) were measured 24 hours after reperfusion.

Results. We found no significant effect of either AQGV (108.7 +/- 12.1 mm3 versus PBS 114.9 +/- 23.9 mm3; P=0.7) or EPPE (131.8 +/-12.8 mm3 versus PBS 114.9 +/- 23.9 mm3

Conclusion. AQGV and EPPE did not show any beneficial effects in this mouse model of acute ischemic stroke. Further studies are needed to investigate the nature and dynamics of the immunomodulatory effects of synthetic oligopeptides in acute ischemic stroke. ; P=0.1) on direct lesion volume. All three experimental groups displayed similar mRNA expression levels of TNF-α, IL-6, E-selectin and ICAM-1 at 24 hours after the ischemic insult.