Recombinant Osteopontin Attenuates Brain Injury after Intracerebral Hemorrhage in Mice
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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.
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.
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.
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.
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- Recombinant Osteopontin Attenuates Brain Injury after Intracerebral Hemorrhage in Mice
Volume 14, Issue 1 , pp 109-117
- Cover Date
- Print ISSN
- Online ISSN
- Humana Press Inc
- Additional Links
- Brain edema
- Intracerebral hemorrhage
- Inducible nitric oxide synthase
- Industry Sectors
- Author Affiliations
- 1. Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, 92350, USA
- 4. Department of Neurology, Affiliated Hospital, North Sichuan Medical College, Nanchong City, Sichuan, China
- 2. Department of Neurosurgery, Loma Linda University, Loma Linda, CA, 92350, USA
- 3. Department of Anesthesiology, Loma Linda University, Loma Linda, CA, 92350, USA
- 5. Department of Physiology, Loma Linda University School of Medicine, Risley Hall, Room 223, Loma Linda, CA, 92354, USA