PO-0472 Evaluation Of Secretoneurin As Therapeutic Strategy In Neonatal Excitotoxic Brain Injury

Abstract

Background Preterm brain injury causes neurodevelopmental disability. Excitotoxicity plays an important role in the pathogenesis of preterm brain injury. The neuropeptide secretoneurin (SN) was shown to enhance angiogenesis and neurogenesis in a rodent model of adult ischaemic brain damage. SN might be considered a promising substance in newborn brain injury. Aim To evaluate the effect of SN as a therapeutic strategy in an established in vivo model of excitotoxic newborn brain injury. Methods Five-day-old mice pups were subjected to an intracranial injection of ibotenic acid into the right brain hemisphere. After recovery for one hour, animals were randomly treated with an intraperitoneal injection of i) vehicle, ii) SN 0.25 µg/g body weight (bw) or iii) SN 2.5 µg/g bw. Brains were harvested 24 and 120 h after the insult and processed for histological analysis. As a primary outcome parameter lesion size in cortical grey and white matter was evaluated. Results SN administration had no significant effect on lesion size 120 h after the insult. When evaluated 24 h after the excitotoxic insult, SN showed a marked, but non-significant trend towards a decreased lesion size in white matter (SN 0.25 µg/g 323.33 ± 128.82, SN 2.5 µg/g bw 298.46 ± 137.46, vehicle 440.00 ± 227.81, n = 13–19, p = 0.06). SN had no effect on lesion size in grey matter. Conclusion This study shows a trend towards a reduced injury in white matter in an in vivo model of neonatal brain injury. We are currently performing immunohistochemical analysis to evaluate underlying mechanisms that could result in long-term protection.