PMID- 9263215 OWN - NLM STAT- MEDLINE DCOM- 19970929 LR - 20190920 IS - 0161-6412 (Print) IS - 0161-6412 (Linking) VI - 19 IP - 4 DP - 1997 Aug TI - Effect of tumor necrosis factor-alpha on the permeability of bovine brain microvessel endothelial cell monolayers. PG - 369-76 AB - The administration of chemotherapy to patients with tumors of the central nervous system is often blocked by the blood-brain barrier. Tumor necrosis factor-alpha (TNF-alpha) is a cytokine that promotes vascular permeability in addition to its pro-inflammatory effects. However, no direct evidence exists as to whether TNF-alpha may increase permeability of the BBB. We evaluated the effect of TNF-alpha on the transport of cisplatin (CDDP) or high molecular weight dextran labeled with fluorescein isothiocyanate (FITC-dextran) across bovine brain microvessel endothelial cell (BMEC) monolayers that was conducted on side-by-side diffusion chambers in vitro. The permeability coefficient for the transport of CDDP across the untreated monolayer was 3.80 x 10(-5) cm sec-1 at 30 minutes. After treating the BMEC monolayer with TNF-alpha (50 U ml-1 and 500 U ml-1) for 36 hours, the PC of CDDP increased significantly to 8.94 x 10(-5), and 14.43 x 10(-5) cm sec-1 respectively (p < 0.01). TNF-alpha had no effect on the transport of FITC-dextran across the BMEC monolayers. Electron microscopy showed that the tight junctions between the BMECs persisted even after treatment with TNF-alpha, whereas they had been partially disrupted following exposure to mannitol, 1600 mOsm kg-1. TNF-alpha selectively promoted the in vitro permeability of the blood-brain barrier to CDDP without disrupting tight junctions. This system could be used as a model for experimental studies of chemotherapy. Findings suggested that the combined administration of TNF-alpha and CDDP may be clinically useful. FAU - Anda, T AU - Anda T AD - Department of Neurosurgery, Nagasaki University School of Medicine, Japan. FAU - Yamashita, H AU - Yamashita H FAU - Khalid, H AU - Khalid H FAU - Tsutsumi, K AU - Tsutsumi K FAU - Fujita, H AU - Fujita H FAU - Tokunaga, Y AU - Tokunaga Y FAU - Shibata, S AU - Shibata S LA - eng PT - Journal Article PL - England TA - Neurol Res JT - Neurological research JID - 7905298 RN - 0 (Antineoplastic Agents) RN - 0 (Dextrans) RN - 0 (Diuretics, Osmotic) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (fluorescein isothiocyanate dextran) RN - 3OWL53L36A (Mannitol) RN - I223NX31W9 (Fluorescein-5-isothiocyanate) RN - Q20Q21Q62J (Cisplatin) SB - IM MH - Animals MH - Antineoplastic Agents/*pharmacokinetics MH - Blood-Brain Barrier/*drug effects MH - Brain/*blood supply MH - Cattle MH - Cells, Cultured MH - Cisplatin/*pharmacokinetics MH - Dextrans/pharmacokinetics MH - Diffusion Chambers, Culture MH - Diuretics, Osmotic/pharmacology MH - Endothelium, Vascular/cytology/drug effects/ultrastructure MH - Fluorescein-5-isothiocyanate/analogs & derivatives/pharmacokinetics MH - Mannitol/pharmacology MH - Microscopy, Electron MH - Tumor Necrosis Factor-alpha/*pharmacology EDAT- 1997/08/01 00:00 MHDA- 1997/08/01 00:01 CRDT- 1997/08/01 00:00 PHST- 1997/08/01 00:00 [pubmed] PHST- 1997/08/01 00:01 [medline] PHST- 1997/08/01 00:00 [entrez] AID - 10.1080/01616412.1997.11758599 [doi] PST - ppublish SO - Neurol Res. 1997 Aug;19(4):369-76. doi: 10.1080/01616412.1997.11758599.