Neurocritical Care

, Volume 14, Issue 1, pp 109–117

Recombinant Osteopontin Attenuates Brain Injury after Intracerebral Hemorrhage in Mice

  • Bihua Wu
  • Qingyi Ma
  • Hidenori Suzuki
  • Chunhua Chen
  • Wenwu Liu
  • Jiping Tang
  • John Zhang
Translational Research

DOI: 10.1007/s12028-010-9372-z

Cite this article as:
Wu, B., Ma, Q., Suzuki, H. et al. Neurocrit Care (2011) 14: 109. doi:10.1007/s12028-010-9372-z

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 edemaCollagenaseIntracerebral hemorrhageInducible nitric oxide synthaseOsteopontin

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Bihua Wu
    • 1
    • 4
  • Qingyi Ma
    • 1
  • Hidenori Suzuki
    • 1
  • Chunhua Chen
    • 1
  • Wenwu Liu
    • 1
  • Jiping Tang
    • 1
  • John Zhang
    • 1
    • 2
    • 3
    • 5
  1. 1.Department of Physiology and PharmacologyLoma Linda UniversityLoma LindaUSA
  2. 2.Department of NeurosurgeryLoma Linda UniversityLoma LindaUSA
  3. 3.Department of AnesthesiologyLoma Linda UniversityLoma LindaUSA
  4. 4.Department of NeurologyAffiliated Hospital, North Sichuan Medical CollegeNanchong CityChina
  5. 5.Department of PhysiologyLoma Linda University School of MedicineLoma LindaUSA