Plasmalemmal Vesicle Associated Protein-1 (PV-1) is a marker of blood-brain barrier disruption in rodent models

We demonstrate that PV-1 is selectively upregulated in mouse blood vessels recruited by brain tumor xenografts at the RNA and protein levels, but is not detected in non-neoplastic brain. Additionally, PV-1 is induced in a mouse model of acute ischemia. Expression is confined to the cerebovasculature within the region of infarct and is temporally regulated.Our results confirm that PV-1 is preferentially induced in the endothelium of mouse brain tumors and acute ischemic brain tissue and corresponds to blood-brain barrier disruption in a fashion analogous to human patients. Characterization of PV-1 expression in mouse brain is the first step towards development of rodent models for testing anti-edema and anti-angiogenesis therapeutic strategies based on this molecule.Vasogenic cerebral edema causes significant morbidity and mortality in patients with malignant brain tumors. Cytokines secreted by the growing tumor such as VEGF, PDGF, and SF/HGF increase the permeability of the blood-brain barrier (BBB) causing extracellular fluid accumulation. The increase in extracellular fluid, in turn, raises intracranial pressure leading eventually to brain ischemia, herniation, and death. The situation repeats itself in the setting of cerebral infarction where the initial intracellular swelling associated with cytotoxic edema is later compounded by cytokine release and vasogenic edema. Clinical attempts to block these cascades have focused on inhibiting signal transduction by the circulating cytokines, including monoclonal antibodies targeted to VEGF and selective receptor tyrosine kinase inhibitors. An equally attractive approach may be to identify selective targets on the endothelial cells themselves, which are associated with BBB alterations.In our previous studies of blood-brain barrier breakdown and endothelial changes in malignant glioma, we have described several microvascular endothelial genes associated with BBB alterations. Using this approach, PV-1 was identified as a G