Entwicklung von in vitro-Methoden als Ersatz von Tierversuchen in der praeklinischen Schlaganfallforschung. Teilprojekt 2: In vitro-Modell der Blut-Hirnschranke Abschlussbericht

Abstract

The blood-brain barrier (BBB) formed by brain capillary endothelial cells (BEC) under the influence of astrocytes (AC) has been neglected in the treatment of blood flow disturbances of the brain, such as ischemia and related injury. On the other hand, these cells can be reached easily by systemic administration of a drug. Among others (i.e., accumulation of cellular Ca"2"+, energy deficiency), reactive oxygen species play an important pathogenic role under ischemic conditions. Therefore, a test hierarchy was developed based on BEC, AC and cocultures of both, which allows to characterized a potentially protective agent with respect to: radical scavenger activity, cytotoxicity, cytoprotectivity against oxidative (hypoxic) stress, and protectivity on the tightness of a cell culture model of the BBB under hypoxic conditions. Moreover, the permeability of test compounds through the BBB model can be determined to predict the permeation of substances into the brain. This test system was validated using neuroprotective agents of different classes and various radical scavengers as research standards. The research strategy described here is expected to partly replace animal experiments in the development of novel neuroprotective drugs. (orig.)SIGLEAvailable from TIB Hannover: F00B620 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung und Forschung (BMBF), Bonn (Germany)DEGerman