| Abstract [eng] |
Blood-brain barrier (BBB) controls the molecular exchange between the brain parenchyma and blood circulation, and prevents the entry of toxins, pathogens, inflammatory factors into the central system. The BBB is a multicomponent structure based on brain microvascular endothelial cells (BMECs), which, together with pericytes, neurons, astrocytes, and microglia, form the neurogliovascular unit. Currently, little is known about the effect of microglia on the functional properties of the BBB under physiological conditions. In this thesis the effects of microglial paracrine factors on the barrier properties of brain microvascular endothelial cells were compared in physiological and inflammatory conditions. BMECs differentiated from human induced pluripotent stem cells were used for in vitro models of BBB. Co-cultivation experiments showed that physiological (non-activated, "resting") microglia statistically significantly increased the transendothelial resistance of BMEC monolayer at late stages of co-cultivation. Meanwhile, inflamed microglia (activated with 20 ng/ml tumor necrosis factor α (TNFα)) negatively affected the barrier properties of BMEC. Our results indicate that extracellular vesicles (exosomes and microvesicles) secreted by „resting“ and activated microglia are not responsible for the effects we observed in BMEC and microglia co-cultures. In addition, the effects mediated by microglial paracrine factors were also not dependent on interactions between BMEC and microglia. The obtained results show that microglia in the "resting" state secrete paracrine factors that improve the barrier properties of BMEC. This data suggests that under physiological conditions microglial paracrine factors may be important in maintaining the functionality of the BBB. |
