TY - GEN
T1 - Effects of recombinant osteopontin on blood-brain barrier disruption after subarachnoid hemorrhage in rats
AU - Suzuki, Hidenori
AU - Hasegawa, Yu
AU - Ayer, Robert
AU - Sugawara, Takashi
AU - Chen, Wanqiu
AU - Sozen, Takumi
AU - Kanamaru, Kenji
AU - Taki, Waro
AU - Zhang, John H.
N1 - Funding Information:
This study was partially supported by NIH NS053407 to J.H. Zhang. Conflict of interest statement We declare that we have no conflict of interest.
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
KW - Blood-brain barrier
KW - Brain injury
KW - Osteopontin
KW - Subarachnoid hemorrhage
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U2 - 10.1007/978-3-7091-0693-8_39
DO - 10.1007/978-3-7091-0693-8_39
M3 - Conference contribution
C2 - 21725761
SN - 9783709106921
T3 - Acta Neurochirurgica, Supplementum
SP - 231
EP - 236
BT - Intracerebral Hemorrhage Research
PB - Springer-Verlag Wien
ER -