Translational Research

Neurocritical Care

, Volume 14, Issue 1, pp 109-117

Recombinant Osteopontin Attenuates Brain Injury after Intracerebral Hemorrhage in Mice

  • Bihua WuAffiliated withDepartment of Physiology and Pharmacology, Loma Linda UniversityDepartment of Neurology, Affiliated Hospital, North Sichuan Medical College
  • , Qingyi MaAffiliated withDepartment of Physiology and Pharmacology, Loma Linda University
  • , Hidenori SuzukiAffiliated withDepartment of Physiology and Pharmacology, Loma Linda University
  • , Chunhua ChenAffiliated withDepartment of Physiology and Pharmacology, Loma Linda University
  • , Wenwu LiuAffiliated withDepartment of Physiology and Pharmacology, Loma Linda University
  • , Jiping TangAffiliated withDepartment of Physiology and Pharmacology, Loma Linda University
  • , John ZhangAffiliated withDepartment of Physiology and Pharmacology, Loma Linda UniversityDepartment of Neurosurgery, Loma Linda UniversityDepartment of Anesthesiology, Loma Linda UniversityDepartment of Physiology, Loma Linda University School of Medicine Email author 

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract

Background

Osteopontin (OPN), an extracellular matrix glycoprotein, has been reported to inhibit inducible nitric oxide synthase (iNOS). We examined if recombinant OPN (r-OPN) inhibits iNOS and prevents brain injury in a mouse collagenase-induced intracerebral hemorrhage (ICH) model.

Methods

One hundred one mice were randomly assigned to five groups: sham, ICH + vehicle, ICH + r-OPN (10, 50, or 100 ng per mouse) groups. Vehicle or r-OPN was administered via an intracerebroventricular infusion 20 min pre-ICH. Neurological scores and brain water content were evaluated at 24 and 72 h, and hemoglobin assay, Nissl staining and Western blot for iNOS, Stat1, matrix metalloproteinase (MMP)-9 and zonula occludens (ZO)-1 were performed at 24 h post-ICH.

Results

r-OPN did not affect hematoma formation. Middle (50 ng)- and high (100 ng)-dose, but not low (10 ng)-dose of r-OPN treatment significantly improved neurological scores and brain water content compared with the vehicle group. The protective effect of r-OPN was associated with significantly rescued neuronal cells in the peri-hematoma region as well as a decrease in the Stat1 phosphorylation, iNOS induction, MMP-9 activation, and ZO-1 degradation.

Conclusions

This study suggests that r-OPN may down-regulate iNOS expression by the inhibition of Stat1 phosphorylation, and therefore suppressing the MMP-9 activation, preventing ICH-induced brain injury in mice.

Keywords

Brain edema Collagenase Intracerebral hemorrhage Inducible nitric oxide synthase Osteopontin