Tumor Necrosis Factor-α Mediates the Blood–Brain Barrier Dysfunction Induced by Activated Microglia in Mouse Brain Microvascular Endothelial Cells

• Published in: Journal of Pharmacological Sciences Vol. 112; no. 2; pp. 251 - 254
• Main Authors: Nishioku, Tsuyoshi, Matsumoto, Junichi, Dohgu, Shinya, Sumi, Noriko, Miyao, Kenji, Takata, Fuyuko, Shuto, Hideki, Yamauchi, Atsushi, Kataoka, Yasufumi
• Format: Journal Article
• Language: English
• Published: Japan Elsevier B.V 2010; The Japanese Pharmacological Society; Elsevier
• Subjects: Animals; Blood-Brain Barrier - metabolism; Blood-Brain Barrier - physiopathology; blood–brain barrier; Brain - blood supply; Brain - metabolism; Capillaries - metabolism; Cell Membrane Permeability; Coculture Techniques; Endothelium, Vascular - metabolism; Fluorescein - pharmacokinetics; Lipopolysaccharides - pharmacology; Mice; Mice, Inbred BALB C; microglia; Microglia - metabolism; Tumor Necrosis Factor-alpha - metabolism; tumor necrosis factor-α (TNF-α); microglia; tumor necrosis factor-α (TNF-α); blood–brain barrier
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1254/jphs.09292SC

The present study was designed to elucidate the involvement of tumor necrosis factor-α (TNF-α) release from activated microglia in the induction of blood–brain barrier (BBB) dysfunction in an in vitro co-culture system with mouse brain capillary endothelial cells (MBEC4) and microglia. Lipopolysaccharide (LPS)–activated microglia increased the permeability of MBEC4 cells to sodium-fluorescein, and this hyper-permeability was blocked by a neutralizing antibody against TNF-α. LPS stimulated microglia to facilitate TNF-α release. These findings suggested that TNF-α released from activated microglia is attributable to BBB dysfunction.