title: Cooling treatment transiently increases the permeability of brain capillary endothelial cells through translocation of claudin-5.
abstract: The blood-brain-barrier (BBB) is formed by different cell types, of which brain microvascular endothelial cells are major structural constituents. The goal of this study was to examine the effects of cooling on the permeability of the BBB with reference to tight junction formation of brain microendothelial cells. The sensorimotor cortex above the dura mater in adult male Wistar rats was focally cooled to a temperature of 5 °C for 1 h, then immunostaining for immunoglobulin G (IgG) was performed to evaluate the permeability of the BBB. Permeability produced by cooling was also evaluated in cultured murine brain endothelial cells (bEnd3) based on measurement of trans-epithelial electric resistance (TEER). Immunocytochemistry and Western blotting of proteins associated with tight junctions in bEnd3 were performed to determine protein distribution before and after cooling. After focal cooling of the rat brain cortex, diffuse immunostaining for IgG was observed primarily around the small vasculature and in the extracellular spaces of parenchyma of the cortex. In cultured bEnd3, TEER significantly decreased during cooling (15 °C) and recovered to normal levels after rewarming to 37 °C. Immunocytochemistry and Western blotting showed that claudin-5, a critical regulatory protein for tight junctions, was translocated from the membrane to the cytoplasm after cooling in cultured bEnd3 cells. These results suggest that focal brain cooling may open the BBB transiently through an effect on tight junctions of brain microendothelial cells, and that therapeutically this approach may allow control of BBB function and drug delivery through the BBB.
authors: Department of Neurosurgery, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan.
authors: Akinori
authors: A
authors: Inamura
authors: Yasuhiro
authors: Y
authors: Adachi
authors: Takao
authors: T
authors: Inoue
authors: Yeting
authors: Y
authors: He
authors: Nobuko
authors: N
authors: Tokuda
authors: Takashi
authors: T
authors: Nawata
authors: Satoshi
authors: S
authors: Shirao
authors: Sadahiro
authors: S
authors: Nomura
authors: Masami
authors: M
authors: Fujii
authors: Eiji
authors: E
authors: Ikeda
authors: Yuji
authors: Y
authors: Owada
authors: Michiyasu
authors: M
authors: Suzuki
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply* / Q000378:metabolism; D002199:Capillary Permeability; D002460:Cell Line; D062507:Claudin-5 / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology*; D007036:Hypothermia, Induced; D008297:Male; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D014655:Vascular Resistance
chemical_list: D062507:Claudin-5; C491510:Cldn5 protein, rat
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