Abstract
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.
Highlights
The blood-brain barrier (BBB) consists of brain microvascular endothelial cells that are surrounded and supported by astrocytes and pericytes
These results showed that heat stress could impair BBB integrity by decreasing the expression of claudin-5
Serum from a mouse model of heatstroke could influence of BBB permeability In Figs 2 and 3, we examined the direct effects of heat stress on induced pluripotent stem (iPS) cell-derived brain microvascular endothelial cells
Summary
The blood-brain barrier (BBB) consists of brain microvascular endothelial cells that are surrounded and supported by astrocytes and pericytes. It plays critical roles in brain homeostasis and neural function by regulating the transfer of substances from the peripheral circulation into the brain. Brain microvascular endothelial cells show high trans-endothelial electrical resistance (TEER) and express selective influx and efflux transporters, for the import and export of molecules, respectively. BBB dysfunction is associated with many neurological diseases, such as multiple sclerosis and traumatic brain injury [1,2,3]. It is well known that heat stress impairs intestinal barrier integrity by increasing intestinal permeability and reducing epithelial resistance [5, 6]
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