An increasing amount of studies have provided evidence for
vascular remodeling, for example, angiogenesis, after
cerebral ischemia, which may play a significant role in post-
stroke brain plasticity and recovery. Molecular imaging can provide unique in vivo whole-brain information on alterations in the expression of specific endothelial markers. A possible target for molecular magnetic resonance imaging (MRI) of post-
stroke (neo)vascularization is
platelet endothelial cell adhesion molecule-1 (PECAM-1). Here we describe significantly increased
PECAM-1 mRNA levels in ipsilesional brain tissue at 6 h, 24 h and 3 days after transient
middle cerebral artery occlusion in mice, and elevated
PECAM-1 staining throughout the lesion at 3, 7 and 21 days post-
stroke. The potential of micron-sized particles of
iron oxide (MPIO) conjugated with PECAM-1-targeted
antibodies, that is, αPECAM-1-MPIO, to expose
stroke-induced
PECAM-1 upregulation with molecular MRI was assessed. In vitro studies demonstrated that PECAM-1-expressing brain endothelial cells could be effectively labeled with αPECAM-1-MPIO, giving rise to a fourfold increase in MRI relaxation rate R2. Injection of near-infrared
fluorescent dye-labeled αPECAM-1 showed target specificity and dose efficiency of the antibody for detection of brain endothelial cells at 3 days post-
stroke. However, in vivo molecular MRI at 3 and 7 days after
stroke revealed no αPECAM-1-MPIO-based contrast enhancement, which was corroborated by the absence of αPECAM-1-MPIO in post mortem brain tissue. This indicates that this molecular MRI approach, which has been proven successful for in vivo detection of other types of
cell adhesion molecules, is not invariably effective for MRI-based assessment of
stroke-induced alterations in expression of cerebrovascular markers.