title: Neuroprotective effect of neotrofin in a neonatal rat model of periventricular leukomalacia.
abstract: Periventricular leukomalacia (PVL) is the dominant form of brain injury in premature infants and no specific treatment is currently available. Neotrofin, a neurotrophin agonist, has been shown to provide neuroprotection in several in vivo and in vitro studies. The aim of this study was to investigate the neuroprotective effect of neotrofin treatment after endotoxin induced PVL in a rat model. Wistar rat pups were divided into four groups as: (1) control, (2) lipopolysaccharide (LPS)-administered group, (3) LPS-administered and prenatal maternal neotrofin-treated group and (4) LPS-administered and postnatal neotrofin-treated group. Intraperitoneal (i.p.) injection of lipopolysaccharide (LPS) was administered consecutively at the 18th and 19th embryonic days to establish endotoxin-induced PVL model. In the prenatal treatment group dams received an i.p. injection of neotrofin (60 mg/kg) following after the second LPS dose; and in the postnatal treatment group rat pups received i.p. injection of neotrofin (60 mg/kg) at birth. At P7, apoptosis and hypomyelination in periventricular white matter were evaluated by immunohistochemical assessments. The prenatal maternal neotrofin treatment significantly reduced the number of apoptotic cell death and greatly prevented LPS-stimulated loss of hypomyelinization. However, neotrofin treatment in the postnatal period was not as effective as intrauterine treatment. Given our results, neotrofin may be useful in reducing brain injury and possessing clinical relevance for the treatment of white matter injury in newborns.
authors.affiliation: Dokuz Eylul University Medical Faculty, Department of Pediatrics, Division of Neonatology, Izmir, Turkey.
authors.forename: Funda
authors.initials: F
authors.lastname: Tüzün
authors.forename: Pınar
authors.initials: P
authors.lastname: Gencpınar
authors.forename: Seda
authors.initials: S
authors.lastname: Ozbal
authors.forename: Mustafa
authors.initials: M
authors.lastname: Dilek
authors.forename: Bekir Ugur
authors.initials: BU
authors.lastname: Ergur
authors.forename: Nuray
authors.initials: N
authors.lastname: Duman
authors.forename: Hasan
authors.initials: H
authors.lastname: Ozkan
authors.forename: Abdullah
authors.initials: A
authors.lastname: Kumral
mesh_terms: D062365:Aminobenzoates / Q000627:therapeutic use*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007042:Hypoxanthines / Q000627:therapeutic use*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007231:Infant, Newborn; D007969:Leukomalacia, Periventricular / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008431:Maternal-Fetal Exchange; D004676:Myelin Basic Protein / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
chemical_list: D062365:Aminobenzoates; D007042:Hypoxanthines; D008070:Lipopolysaccharides; D004676:Myelin Basic Protein; D018696:Neuroprotective Agents; C086241:4-((3-(1,6-dihyro-6-oxo-9H-purin-9-yl)-1-oxopropyl)amino)benzoic acid; D053148:Caspase 3