title: Administration of secretoneurin is protective in hypoxic-ischemic neonatal brain injury predominantly in the hypoxic-only hemisphere.
abstract: Neonatal brain injury is a problem of global importance. To date, no causal therapies are available. A substance with considerable therapeutic potential is the endogenous neuropeptide secretoneurin (SN), which has proven to be beneficial in adult stroke. The aim of this study was to assess its effect in neonatal hypoxic-ischemic brain injury models. In vitro, primary hippocampal neurons were pre-treated with vehicle, 1µg/ml, 10µg/ml, or 50µg/ml SN and subjected to oxygen-glucose deprivation (OGD) for six hours. Cell death was assessed after a 24-h recovery period. In vivo, seven day-old CD-1 mice underwent unilateral common carotid artery ligation and were exposed to 8% oxygen/nitrogen for 20 min. SN plasma concentrations were serially determined by ELISA after insult. One hour after hypoxia, a subgroup of animals was treated with vehicle or SN. SN plasma concentrations significantly decreased 48h after insult. The number of caspase-3-positive cells was significantly lower in the hypoxic-ischemic hemisphere in the thalamus of SN-treated animals. In the hypoxic-only hemisphere administration of SN significantly reduced the number of caspase-3-positive cells (in cortex, white matter, hippocampus, thalamus and striatum) and inhibited microglial cell activation in the thalamus. SN has neuroprotective potential in neonatal brain injury. Its main action seems to be inhibition of apoptosis in the aftermath of the insult, predominantly in the hypoxic-only hemisphere. This might be explained by the less pronounced injury in this hemisphere, where blood flow and thus nutrient supply are maintained.
authors.affiliation: Pediatrics II (Neonatology), Department of Pediatrics, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
authors.forename: Anna
authors.initials: A
authors.lastname: Posod
authors.affiliation: Pediatrics II (Neonatology), Department of Pediatrics, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
authors.forename: Karina
authors.initials: K
authors.lastname: Wechselberger
authors.affiliation: Division of Physiology, Department of Physiology and Medical Physics, Medical University of Innsbruck, Schöpfstrasse 41, 6020 Innsbruck, Austria.
authors.forename: Ruslan Iljitsch
authors.initials: RI
authors.lastname: Stanika
authors.affiliation: Division of Physiology, Department of Physiology and Medical Physics, Medical University of Innsbruck, Schöpfstrasse 41, 6020 Innsbruck, Austria.
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Obermair
authors.affiliation: Pediatrics II (Neonatology), Department of Pediatrics, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
authors.forename: Karina
authors.initials: K
authors.lastname: Wegleiter
authors.affiliation: Pediatrics II (Neonatology), Department of Pediatrics, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
authors.forename: Eva
authors.initials: E
authors.lastname: Huber
authors.affiliation: Pediatrics II (Neonatology), Department of Pediatrics, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
authors.forename: Martina
authors.initials: M
authors.lastname: Urbanek
authors.affiliation: Pediatrics II (Neonatology), Department of Pediatrics, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
authors.forename: Ursula
authors.initials: U
authors.lastname: Kiechl-Kohlendorfer
authors.affiliation: Pediatrics II (Neonatology), Department of Pediatrics, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. Electronic address: elke.griesmaier@i-med.ac.at.
authors.forename: Elke
authors.initials: E
authors.lastname: Griesmaier
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001930:Brain Injuries / Q000209:etiology* / Q000517:prevention & control*; D053148:Caspase 3 / Q000378:metabolism; D018929:Cell Culture Techniques; D015687:Cell Hypoxia / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D007839:Functional Laterality / Q000187:drug effects*; D005947:Glucose / Q000172:deficiency; D006624:Hippocampus / Q000166:cytology; D020925:Hypoxia-Ischemia, Brain / Q000097:blood / Q000150:complications*; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D009474:Neurons / Q000187:drug effects; D009479:Neuropeptides / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D053381:Secretogranin II / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D009479:Neuropeptides; D018696:Neuroprotective Agents; D018809:Proliferating Cell Nuclear Antigen; D053381:Secretogranin II; C081159:secretoneurin; D053148:Caspase 3; D005947:Glucose
keywords: hypoxia–ischemia; hypoxic-only; neonatal brain injury; neuropeptide; neuroprotection; secretoneurin