biostudies-literatureUnknown16(10)Chim SMRegeneron Pharmaceuticals, Inc.<b>Background/Objectives:</b> The limited translatability of preclinical experimental findings to patients remains an obstacle for successful treatment of brain diseases. Relevant models to elucidate mechanisms behind brain pathogenesis, including cell-specific contributions and cell-cell interactions, and support successful targeting and prediction of drug responses in humans are urgently needed, given the species differences in brain and blood-brain barrier (BBB) functions. Human microphysiological systems (MPS), such as Organ-Chips, are emerging as a promising approach to address these challenges. Here, we examined and advanced a Brain-Chip that recapitulates aspects of the human cortical parenchyma and the BBB in one model. <b>Methods:</b> We utilized human primary astrocytes and pericPharmaceutics1314https://www.ebi.ac.uk/biostudies/studies/S-EPMC11510380biostudies-literatureA Human Brain-Chip for Modeling Brain Pathologies and Screening Blood-Brain Barrier Crossing Therapeutic Strategies.PMC11510380Zambrowicz BChim SMKaralis KHowell KKokkosis APavlopoulos EfalseA Human Brain-Chip for Modeling Brain Pathologies and Screening Blood-Brain Barrier Crossing Therapeutic Strategies.<b>Background/Objectives:</b> The limited translatability of preclinical experimental findings to patients remains an obstacle for successful treatment of brain diseases. Relevant models to elucidate mechanisms behind brain pathogenesis, including cell-specific contributions and cell-cell interactions, and support successful targeting and prediction of drug responses in humans are urgently needed, given the species differences in brain and blood-brain barrier (BBB) functions. Human microphysiological systems (MPS), such as Organ-Chips, are emerging as a promising approach to address these challenges. Here, we examined and advanced a Brain-Chip that recapitulates aspects of the human cortical parenchyma and the BBB in one model. <b>Methods:</b> We utilized human primary astrocytes and peric2024-01-01T00:00:00Z2024 Oct2025-04-04T03:03:45.807Z2025-04-04T03:03:45.807ZS-EPMC115103803945864310.3390/pharmaceutics16101314