A second line adding to the selective permeability properties of the BBB is an elaborate system of asymmetrically expressed transport proteins and receptors at the luminal and abluminal membrane of brain MVEC taking a central biochemical gate keeping function at the BBB. We aim to use selected receptor systems to improve payload delivery of drug-loaded nanoparticles across the BBB into deeper regions of the CNS. In the healthy brain several cell types are anatomically and biochemically integrated to guarantee normal function of the CNS. However, under chronic inflammatory conditions astrocytes and microglia can potentiate neuronal injury by enhanced production of reactive oxygen-, nitrogen-, and chlorinating species. Along this line we are interested in activation mechanisms of myeloperoxidase (MPO) in astrocytes and microglia. In the presence of physiological chloride concentrations, hydrogen peroxide serves as co-substrate for MPO and is converted to potent oxidant hypochlorous acid (HOCl). HOCl favors the modification of unsaturated lipids, thereby generating modified compounds with lipotoxic properties that potentially inflict bystander damage in the brain. We are investigating signaling pathways in brain MVEC and neurons that are evoked in response to selected HOCl-/MPO-modified lipids (http://lipotox.uni-graz.at). A fourth major goal of our group is to understand (lipid-dependent) signaling pathways driving glioma growth. The prognosis for patients with malignant gliomas - where astrocytic gliomas have the highest incidence - remains dismal: median post-treatment survival of patients suffering anaplastic astrocytoma is between two and three years and that of glioblastoma patients is between nine and twelve months. One of the many problems encountered in brain tumor treatment is the tightness of the BBB protecting the CNS against traditional cytostatic agents. In this project we aim to inhibit glioblastoma growth by RNA-interference and to establish BBB-permeable delivery vehicles.