02266nas a2200253   4500000000100000008004100001260001500042653001900057653001900076653002300095653002000118653003000138653000900168100001900177700001700196700001900213700002000232245008500252856007200337300001100409490000800420520157000428022001401998       2023                            d  c2023-07-0110abrain organoid10aBrain spheroid10aIn-vitro infection10aInfection model10amicrophysiological system10aiPSC1 aPaula Barreras1 aDavid Pamies1 aThomas Hartung1 aCarlos A. Pardo00aHuman brain microphysiological systems in the study of neuroinfectious disorders  uhttps://www.sciencedirect.com/science/article/pii/S0014488623000936  a1144090 v3653 aMicrophysiological systems (MPS) are 2D or 3D multicellular constructs able to mimic tissue microenvironments. The latest models encompass a range of techniques, including co-culturing of various cell types, utilization of scaffolds and extracellular matrix materials, perfusion systems, 3D culture methods, 3D bioprinting, organ-on-a-chip technology, and examination of tissue structures. Several human brain 3D cultures or brain MPS (BMPS) have emerged in the last decade. These organoids or spheroids are 3D culture systems derived from induced pluripotent cells or embryonic stem cells that contain neuronal and glial populations and recapitulate structural and physiological aspects of the human brain. BMPS have been introduced recently in the study and modeling of neuroinfectious diseases and have proven to be useful in establishing neurotropism of viral infections, cell-pathogen interactions needed for infection, assessing cytopathological effects, genomic and proteomic profiles, and screening therapeutic compounds. Here we review the different methodologies of organoids used in neuroinfectious diseases including spheroids, guided and unguided protocols as well as microglia and blood-brain barrier containing models, their specific applications, and limitations. The review provides an overview of the models existing for specific infections including Zika, Dengue, JC virus, Japanese encephalitis, measles, herpes, SARS-CoV2, and influenza viruses among others, and provide useful concepts in the modeling of disease and antiviral agent screening.  a0014-4886