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Y-P30 is a polypeptide survival promoting factor that has significant impact on the survival and differentiation of neurons in the developing brain. To address its potential role in brain injury we tested its neuroprotective effects in the oxygen-glucose deprivation (OGD) model with hippocampal slice cultures as an in vitro assay for ischemia. We could demonstrate that supplementation with Y-P30 leads to a significant neuroprotection at concentrations of 200 nM and 2 microM when it was added to the medium of hippocampal slice cultures 2 h before starting the deprivation of oxygen and glucose. A significant neuroprotective effect was found when the peptide was applied 2 h after injury. Y-P30 oligomerises in large complexes, which might hinder the passage through the culture membranes in our system. We therefore also applied Y-P30 directly on the hippocampal slices, which led to the most robust neuroprotection even at very low concentrations.