The Transmitter, Год журнала: 2024, Номер unknown
Опубликована: Янв. 1, 2024
Язык: Английский
Handbook of clinical neurology, Год журнала: 2025, Номер unknown, С. 269 - 285
Опубликована: Янв. 1, 2025
Язык: Английский
Процитировано
0
Journal of Neuroinflammation, Год журнала: 2025, Номер 22(1)
Опубликована: Апрель 3, 2025
Abstract Prenatal immune challenges pose significant risks to human embryonic brain and eye development. However, our knowledge about the safe usage of anti-inflammatory drugs during pregnancy is still limited. While induced pluripotent stem cells (hIPSC)-derived organoid models have started explore functional consequences upon viral stimulation, these commonly lack microglia, which are susceptible promote inflammation. Furthermore, microglia actively involved in neuronal Here, we generate hIPSC-derived precursor assemble them into retinal organoids. Once outer plexiform layer forms, (iMG) fully integrate Since ganglion cell survival declines by this time 3D-retinal organoids, adapted model 2D identify that improved number significantly decreases only with iMG presence. In parallel, applied immunostimulant POLY(I:C) mimic a fetal infection. exposure alters phenotype, it does not hinder their interaction cells. enhance supernatant’s inflammatory secretome increase proliferation. Simultaneous non-steroidal drug (NSAID) ibuprofen dampens POLY(I:C)-mediated changes phenotype ameliorates Remarkably, while disrupts calcium dynamics independent iMG, rescues effect if present. Mechanistically, targets enzymes cyclooxygenase 1 2 ( COX1/PTGS1 COX2/PTGS2 ) simultaneously, from mainly express COX1 . Selective blockage fails restore peak amplitude suggesting ibuprofen’s beneficial depends on presence interplay COX2 These findings underscore importance context prenatal provide insight mechanisms exerts its protective effects
Язык: Английский
Процитировано
0
The Transmitter, Год журнала: 2024, Номер unknown
Опубликована: Янв. 1, 2024
Язык: Английский
Процитировано
0