Abstract
Ischemic stroke is a major, urgent neurologic disorder in which reactive oxygen species (ROS) are deeply involved in the detrimental effects. Platinum nanoparticle (nPt) species are a novel and strong scavenger of such ROS, so we examined the clinical and neuroprotective effects of nPts in mouse ischemic brain. Mice were subjected to transient middle cerebral artery occlusion (tMCAO) for 60 min. Upon reperfusion, nPt or vehicle was administered intravenously. At 48 hr after the tMCAO, motor function, infarct volume, immunohistochemistry of neurovascular components (endothelial NAGO, tight junctional occludin, and basal laminal collagen IV), and zymography for MMP-9 activity were examined. Superoxide anion generation at 2 hr after tMCAO was determined with oxidized hydroethidine. Compared with vehicle, treatment with nPts significantly improved the motor function and greatly reduced the infarct volume, especially in the cerebral cortex. Immunohistochemical analyses revealed that tMCAO resulted in a minimal decrease of NAGO and occludin but a great decrease of collagen IV and a remarkable increase of MMP-9. Treatment with nPts greatly reduced this decrease of collagen IV and activation of MMP-9 and, with large reductions of MMP-9 activation on zymography and superoxide production. The present study demonstrates that treatment with nPts ameliorates the neurological scores with a large reduction in infarct size as well as the preservation of outer components of the neurovascular unit (collagen IV) and inactivation of MMP-9. A strong reduction of superoxide anion production by nPts could account for such remarkable neurobehavioral and neuroprotective effects on ischemic stroke.
| Original language | English |
|---|---|
| Pages (from-to) | 1125-1133 |
| Number of pages | 9 |
| Journal | Journal of Neuroscience Research |
| Volume | 89 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Jul 2011 |
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Keywords
- Cerebral ischemia
- Free radical scavenger
- MMP-9
- Neuroprotection
- Platinum nanoparticles
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience
Cite this
Neurological and pathological improvements of cerebral infarction in mice with platinum nanoparticles. / Takamiya, Motonori; Miyamoto, Yusei; Yamashita, Toru; Deguchi, Kentaro; Ohta, Yasuyuki; Ikeda, Yoshio; Matsuura, Tohru; Abe, Koji.
In: Journal of Neuroscience Research, Vol. 89, No. 7, 07.2011, p. 1125-1133.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Neurological and pathological improvements of cerebral infarction in mice with platinum nanoparticles
AU - Takamiya, Motonori
AU - Miyamoto, Yusei
AU - Yamashita, Toru
AU - Deguchi, Kentaro
AU - Ohta, Yasuyuki
AU - Ikeda, Yoshio
AU - Matsuura, Tohru
AU - Abe, Koji
PY - 2011/7
Y1 - 2011/7
N2 - Ischemic stroke is a major, urgent neurologic disorder in which reactive oxygen species (ROS) are deeply involved in the detrimental effects. Platinum nanoparticle (nPt) species are a novel and strong scavenger of such ROS, so we examined the clinical and neuroprotective effects of nPts in mouse ischemic brain. Mice were subjected to transient middle cerebral artery occlusion (tMCAO) for 60 min. Upon reperfusion, nPt or vehicle was administered intravenously. At 48 hr after the tMCAO, motor function, infarct volume, immunohistochemistry of neurovascular components (endothelial NAGO, tight junctional occludin, and basal laminal collagen IV), and zymography for MMP-9 activity were examined. Superoxide anion generation at 2 hr after tMCAO was determined with oxidized hydroethidine. Compared with vehicle, treatment with nPts significantly improved the motor function and greatly reduced the infarct volume, especially in the cerebral cortex. Immunohistochemical analyses revealed that tMCAO resulted in a minimal decrease of NAGO and occludin but a great decrease of collagen IV and a remarkable increase of MMP-9. Treatment with nPts greatly reduced this decrease of collagen IV and activation of MMP-9 and, with large reductions of MMP-9 activation on zymography and superoxide production. The present study demonstrates that treatment with nPts ameliorates the neurological scores with a large reduction in infarct size as well as the preservation of outer components of the neurovascular unit (collagen IV) and inactivation of MMP-9. A strong reduction of superoxide anion production by nPts could account for such remarkable neurobehavioral and neuroprotective effects on ischemic stroke.
AB - Ischemic stroke is a major, urgent neurologic disorder in which reactive oxygen species (ROS) are deeply involved in the detrimental effects. Platinum nanoparticle (nPt) species are a novel and strong scavenger of such ROS, so we examined the clinical and neuroprotective effects of nPts in mouse ischemic brain. Mice were subjected to transient middle cerebral artery occlusion (tMCAO) for 60 min. Upon reperfusion, nPt or vehicle was administered intravenously. At 48 hr after the tMCAO, motor function, infarct volume, immunohistochemistry of neurovascular components (endothelial NAGO, tight junctional occludin, and basal laminal collagen IV), and zymography for MMP-9 activity were examined. Superoxide anion generation at 2 hr after tMCAO was determined with oxidized hydroethidine. Compared with vehicle, treatment with nPts significantly improved the motor function and greatly reduced the infarct volume, especially in the cerebral cortex. Immunohistochemical analyses revealed that tMCAO resulted in a minimal decrease of NAGO and occludin but a great decrease of collagen IV and a remarkable increase of MMP-9. Treatment with nPts greatly reduced this decrease of collagen IV and activation of MMP-9 and, with large reductions of MMP-9 activation on zymography and superoxide production. The present study demonstrates that treatment with nPts ameliorates the neurological scores with a large reduction in infarct size as well as the preservation of outer components of the neurovascular unit (collagen IV) and inactivation of MMP-9. A strong reduction of superoxide anion production by nPts could account for such remarkable neurobehavioral and neuroprotective effects on ischemic stroke.
KW - Cerebral ischemia
KW - Free radical scavenger
KW - MMP-9
KW - Neuroprotection
KW - Platinum nanoparticles
UR - http://www.scopus.com/inward/record.url?scp=79955573043&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79955573043&partnerID=8YFLogxK
U2 - 10.1002/jnr.22622
DO - 10.1002/jnr.22622
M3 - Article
C2 - 21433052
AN - SCOPUS:79955573043
VL - 89
SP - 1125
EP - 1133
JO - Journal of Neuroscience Research
JF - Journal of Neuroscience Research
SN - 0360-4012
IS - 7
ER -