Effects of recombinant osteopontin on blood-brain barrier disruption after subarachnoid hemorrhage in rats.

Abstract

OBJECTS:

We determined effects of recombinant OPN (r-OPN), a pleiotropic extracellular matrix protein, on blood-brain barrier (BBB) disruption and matrix metalloproteinase (MMP)-9 activation after subarachnoid hemorrhage (SAH) in rats.

METHODS:

The endovascular perforation model of SAH was used. SAH or sham-operated rats were treated with pre-SAH intracerebroventricular administration of two dosages of r-OPN, r-OPN+GRGDSP (an L-arginyl-glycyl-L-aspartate-dependent integrin receptor antagonist), albumin or vehicle. Neurological impairments, brain edema and BBB disruption were evaluated, and Western blot analyses were performed in the brain at 24 h after SAH.

RESULTS:

r-OPN significantly prevented brain edema and BBB disruption compared with the control rats, associated with the suppression of nuclear factor-κB and mitogen-activated protein kinase pathways, leading to MMP-9 inactivation. These effects were blocked by GRGDSP.

CONCLUSIONS:

L-arginyl-glycyl-L-aspartate-dependent integrin receptor-mediated multiple signaling pathways may be involved in the protective effects of r-OPN against BBB disruption after SAH.

• Authors: Hidenori Suzuki, Yu Hasegawa, Robert Ayer, Takashi Sugawara, Wanqiu Chen, Takumi Sozen, Kenji Kanamaru, Waro Taki, John H Zhang
• Journal: Acta neurochirurgica. Supplement (Acta Neurochir Suppl) Vol. 111 Pg. 231-6 ( 2011) ISSN: 0065-1419 [Print] Austria
• PMID: 21725761 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Oligopeptides
• Recombinant Proteins
• Osteopontin
• glycyl-arginyl-glycyl-aspartyl-seryl-proline
• I-kappa B Kinase
• MAP Kinase Kinase 4
• Matrix Metalloproteinase 9

Topics

• Animals
• Blood-Brain Barrier (drug effects, physiopathology)
• Brain Edema (drug therapy, etiology)
• Chi-Square Distribution
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Gene Expression Regulation (drug effects)
• I-kappa B Kinase (metabolism)
• MAP Kinase Kinase 4 (metabolism)
• Male
• Matrix Metalloproteinase 9 (metabolism)
• Nervous System Diseases (drug therapy, etiology)
• Neurologic Examination
• Oligopeptides (therapeutic use)
• Osteopontin (therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Recombinant Proteins (therapeutic use)
• Severity of Illness Index
• Subarachnoid Hemorrhage (drug therapy, pathology)