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

Journal of Neuroinflammation

Xiaoyang Wang¹  Harvey Cantor³  Carina Mallard²  Henrik Hagberg⁵  Lili Qiao⁴  Syam Nair²  Dan Bi¹  Jianmei Leavenworth³  Xiaoli Zhang¹  Anna-Maj Albertsson² 

[1] Department of Pediatrics, The Third Affiliated Hospital of Zhengzhou University, 7 Kangfu Front St, Zhengzhou, 450052, China;Perinatal Center, Department of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, SE-405 30, Sweden;Department of Microbiology and Immunobiology, Division of Immunology, Harvard Medical School, 77 Ave Louis Pasteur, Boston 02115, MA, USA;Department of Pediatrics, Song Jiang Central Hospital, 746 Songjiang Zhongshan West Rd, Shanghai, 201600, China;Department of Perinatal Imaging and Health, Division of Imaging Sciences and Biomedical Engineering, King’s College London, King’s Health Partners, St. Thomas’ Hospital, London SE1 7EH, UK

关键词: Ischemia;    Hypoxia;    Osteopontin;    Brain injury;    Preterm;   

Others  :  1150080
DOI  :  10.1186/s12974-014-0197-0

 received in 2014-06-03, accepted in 2014-11-07,  发布年份 2014

【 摘 要 】

Background

Osteopontin (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.

Methods

We 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.

Results

There 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.

Conclusions

The 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.

【 授权许可】

   
2014 Albertsson et al.; licensee BioMed Central Ltd.

【 图 表 】

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