AN IN-VITRO MODEL OF THE BLOOD-BRAIN-BARRIER - THE RESPONSE OF MADIN-DARBY CANINE KIDNEY-CELLS TO TRIETHYL TIN

The development of a cell culture model which simulates the properties of the blood-brain barrier (BBB) is necessary for the detection of ne urotoxic chemicals that can disrupt the barrier, and to provide a more ''risk relevant'' in vitro screening battery. The present study evalu ates the Madin-Darby canine kidney (MDCK) epithelial cell line for thi s purpose. Changes in electrical resistance and enzyme activities were correlated in confluent MDCK cells exposed to the neurotoxic metal tr iethyl tin (TET). Concentrations of TET (0.001-10 mu M) were establish ed that produced depression in electrical resistance of the MDCK cells after exposure for 8 hours or caused fluorescein leakage after exposu re for 72 hours. Confluent cultures of MDCK cells were then exposed to these concentrations of TET and assayed after exposure for 24 hours a nd 72 hours for changes in those enzymes common to both epithelial and cerebral endothelial cells. The results indicated that increased alka line phosphatase (APP), gamma-glutamyl transpeptidase (GGTP) and super oxide dismutase (SOD) characterised the loss of electrical resistance and permeability disruption in TET-exposed MDCK confluent cultures. Re lative increases in APP and decreases in GGTP activities preceded cyto toxicity, which was associated with a high SOD activity. Such enzyme c hanges may be predictive endpoints of barrier cell disruption by neuro toxic metals in this cell line and support the additional evaluation o f the MDCK cell line as an in vitro ''screen'' for chemicals that disr upt the BBB.