Recombinant osteopontin attenuates brain injury after intracerebral hemorrhage in mice
Document Type
Article
Publication Date
2-1-2011
Publication Title
Neurocritical care
E-ISSN
1556-0961
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.
Volume
14
Issue
1
First Page
109
Last Page
17
DOI
10.1007/s12028-010-9372-z
PubMed ID
20440599
Recommended Citation
Wu, Bihua; Ma, Qingyi; Suzuki, Hidenori; Chen, Chunhua; Liu, Wenwu; Tang, Jiping; and Zhang, John, "Recombinant osteopontin attenuates brain injury after intracerebral hemorrhage in mice" (2011). Loma Linda University Faculty Publications. 369.
https://scholarsrepository.llu.edu/fac_pubs/369