Open AccessEffect of heat stress on blood-brain barrier integrity in iPS cell-derived microvascular endothelial cell models
Author(s) -
Tomoko Yamaguchi,
Kentaro Shimizu,
Yasuhiro Kokubu,
Masaki Nishijima,
Shuko Takeda,
Hiroshi Ogura,
Kenji Kono
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0222113
Subject(s) - heatstroke , endothelial stem cell , blood–brain barrier , in vivo , microbiology and biotechnology , endothelium , p glycoprotein , in vitro , biology , chemistry , medicine , neuroscience , endocrinology , central nervous system , biochemistry , antibiotics , multiple drug resistance
The incidence of heatstroke has been increasing. Heatstroke has been shown to affect physiological barrier functions. However, there are few studies of the effect of heat stress on the blood-brain barrier (BBB) function. In this study, we investigated the influence of heat stress on brain microvascular endothelial cells in vivo and in vitro . Heatstroke model mice administered Texas Red-dextran showed leakage outside the brain vessel walls. In addition, trans-endothelial electrical resistance (TEER) value was significantly reduced in induced pluripotent stem (iPS) cell-derived brain microvascular endothelial cells under heat stress by reducing claudin-5 expression. In addition, our results showed that the expression level of P-glycoprotein (P-gp) was increased in iPS cell-derived brain microvascular endothelial cells under heat stress. Furthermore, serum from heatstroke model mice could impair the BBB integrity of iPS cell-derived brain microvascular endothelial cells. These results suggest that BBB integrity was affected by heat stress in vivo and in vitro and provide important insights into the development of new therapeutic strategies for heatstroke patients.