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The effect of osteopontin and osteopontin-derived peptides on preterm brain injury.

Journal article
Authors Anna-Maj Albertsson
Xiaoli Zhang
Jianmei Leavenworth
Dan Bi
Syam Nair
Lili Qiao
Henrik Hagberg
Carina Mallard
Harvey Cantor
Xiaoyang Wang
Published in Journal of neuroinflammation
Volume 11
Issue 1
Pages 197
ISSN 1742-2094
Publication year 2014
Published at Institute of Neuroscience and Physiology
Institute of Clinical Sciences, Department of Obstetrics and Gynecology
Pages 197
Language en
Links dx.doi.org/10.1186/s12974-014-0197-...
Keywords Preterm; Brain injury; Osteopontin; Hypoxia; Ischemia
Subject categories Obstetrics and women's diseases

Abstract

BackgroundOsteopontin (OPN) is a highly phosphorylated sialoprotein and a soluble cytokine that is widely expressed in a variety of tissues, including the brain. OPN and OPN-derived peptides have been suggested to have potential neuroprotective effects against ischemic brain injury, but their role in preterm brain injury is unknown.MethodsWe used a hypoxia-ischemia (HI)-induced preterm brain injury model in postnatal day 5 mice. OPN and OPN-derived peptides were given intracerebroventricularly and intranasally before HI. Brain injury was evaluated at 7 days after the insults.ResultsThere was a significant increase in endogenous OPN mRNA and OPN protein in the mouse brain after the induction of HI at postnatal day 5. Administration of full-length OPN protein and thrombin-cleaved OPN did not affect preterm brain injury. This was demonstrated with both intracerebroventricular and intranasal administration of OPN as well as in OPN-deficient mice. Interestingly, both N134¿153 and C154¿198 OPN-derived peptides increased the severity of brain injury in this HI-induced preterm brain injury model.ConclusionsThe neuroprotective effects of OPN are age-dependent, and, in contrast to the more mature brain, OPN-derived peptides potentiate injury in postnatal day 5 mice. Intranasal administration is an efficient way of delivering drugs to the central nervous system (CNS) in neonatal mice and is likely to be an easy and noninvasive method of drug delivery to the CNS in preterm infants.

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