Neuroprotection by a novel immunomodulatory peptide [adult mice]. Mus musculus

Perinatal brain injury is a major clinical problem associated with high neonatal mortality and morbidity and an increased risk of life-long chronic disabilities. Despite improved survival rates, the absolute numbers of neurological handicaps of perinatal origin have not decreased. There is currently no pharmacological treatment providing neuroprotction in neonates. As activation of the innate immune response is a key contributing factor to brain injury in both term and preterm infants we investigated the therapeutic potential of novel immunomodulatory innate defence regulator peptides (IDRs) in perinatal brain injury. IDR-1018 significantly reduced the production of inflammatory mediators by LPS-stimulated microglia cells in vitro. IDR-1018 was also neuroprotective in a clinically-relevant animal model of neonatal brain injury, exerting effects on regulatory molecules of TLR-, Ca2+- and p53-signaling. Of utmost importance, IDR-1018 markedly protected both white and grey brain matter when administered after the injury, thus has tremendous applicability to the clinical setting. Here we demonstrate for the first time that peripheral administration of an immunomodulatory peptide is neuroprotective in vivo in a clinically relevant model of perinatal brain damage. In this second data set, adult mice were used for comparison. Overall design: 5 samples each for 4 groups were used for a total of 20 samples. Groups were: LPS-sensitized hypoxic-ischemic (LPS+HI) with injured (left) and uninjured (right) brain hemispheres, in the presence or absence of peptide IDR1018. The groups are therefore: 1) LPS + HI, left hemisphere, 2) LPS + HI with IDR1018, left hemisphere, 3) LPS + HI, right hemisphere, 4) LPS + HI with IDR1018, right hemisphere.