Reactive oxygen species (ROS) are major exacerbation factor in
acute ischemic stroke, and
thrombolytic agent tissue plasminogen activator (tPA) may worsen motor function and
cerebral infarcts. The
platinum nanoparticle (nPt) is a novel ROS scavenger, and thus we examined the clinical and
neuroprotective effects of nPt in ischemic mouse brains. Mice were subjected to transient
middle cerebral artery occlusion (tMCAO) for 60 min and divided into the following four groups by
intravenous administration upon reperfusion, vehicle, tPA, tPA+nPt, and nPt. At 48 h after tMCAO, motor function,
infarct volume, immunohistochemical analyses of neurovascular unit (NVU), in vivo imaging of
matrix metalloproteinase (
MMP), and zymography for MMP-9 activity were examined.
Superoxide anion generation at 2h after tMCAO was also examined with
hydroethidine (HEt). As a result, administration of tPA deteriorated the motor function and
infarct volume as compared to vehicle. In vivo optical imaging of
MMP showed strong fluorescent signals in affected regions of tMCAO groups. 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. HEt
stain showed increased ROS generation by tMCAO. All these results became pronounced with tPA administration, and were greatly reduced by nPt. The present study demonstrates that nPt treatment ameliorates neurological function and brain damage in acute
cerebral infarction with
neuroprotective effect on NVU and inactivation of MMP-9. The strong reduction of ROS production by nPt could account for these remarkable neurological and
neuroprotective effects against
ischemic stroke.