Among brain tumors, glioblastoma (GBM) is very challenging to treat as chemotherapeutic drugs can only penetrate the brain to a limited extent due to the blood–brain barrier (BBB). Nanoparticles can be an attractive solution for the treatment of GBM as they can transport drugs across the BBB into the tumor. In this study, normal and GBM organoids comprising six brain cell types were developed and applied to study the uptake, BBB penetration, distribution, and efficacy of fluorescent, ultrasmall gold nanoparticles (AuTio-Dox-AF647s) conjugated with doxorubicin (Dox) and AlexaFluor-647-cadaverine (AF647) by confocal laser scanning microscopy (CLSM), using a mixture of dissolved doxorubicin and fluorescent AF647 molecules as a control. It was shown that the nanoparticles could easily penetrate the BBB and were found in normal and GBM organoids, while the dissolved Dox and AF647 molecules alone were unable to penetrate the BBB. Flow cytometry showed a reduction in glioblastoma cells after treatment with AuTio-Dox nanoparticles, as well as a higher uptake of these nanoparticles by GBM cells in the GBM model compared to astrocytes in the normal cell organoids. In summary, our results show that ultrasmall gold nanoparticles can serve as suitable carriers for the delivery of drugs into organoids to study BBB function.

Although it is widely recognized that multisensory integration is a critical neural process underlying normal perception and behavior, estimates of its impact have varied among studies involving different contexts, tasks, and response measures. To address the reliability and magnitude of its effect, analysis was conducted on data from a benchmark visual-auditory detection and localization task used in seven studies using cat as the animal model, spanning 35 years. This extensive dataset enabled a robust evaluation of the magnitude, consistency, and optimality of multisensory integration while including common sources of experimental variability. The results revealed that the multisensory behavioral performance in this paradigm was consistently above the most stringent referent criteria, the sum of the unisensory performance levels. This "superadditive" multisensory effect was consistent with the predictions of an optimal model in which visual and auditory input signals are summed before being nonlinearly transformed into observable behaviors by a decision-making process modeled on signal detection theory. In operational terms, the multisensory effect reflected a consistent proportional enhancement of ∼50 % in behavioral performance and the analysis revealed that there was minimal variance across testing sessions and minimal sensitivity to factors such as animal sex, stimulus location, and trial history. Due to its reliability, significant multisensory effects can be detected with as few as three subjects and 15 trials per test condition (visual, auditory, visual-auditory), highlighting the utility of this paradigm for evaluating the efficiency of this neural process in enhancing functions essential for survival.

Numerous central nervous system pathological conditions involve blood–brain barrier (BBB) disruption and the egress of immune cells in the brain. Controlling immune cell transmigration into the brain represents a potential therapeutic target. This study describes the application of a 3D human BBB spheroidal model that consists of six major brain cell types to test the transmigration of immune cells under normal and pathological conditions of inflammation and ischemia–reperfusion injury (IRI). The cell types in the BBB organoid include brain microvascular endothelial cells (HBMVECs) and pericytes at the spheroids’ surface, surrounding a core of astrocytes, microglia, oligodendrocytes, and neural progenitor cells. The model recapitulates the interaction of CD4⁺ T-cells and immunomodulators with HBMVECs at the BBB including changes in cell adhesion molecules expressed on their surface. This study demonstrated that the human 3D BBB model recapitulates many features of the barrier under normal and pathological conditions of inflammation and hypoxia-reperfusion injury. Proinflammatory cytokines and hypoxia disrupt the barrier and increase its permeability, decreasing the expression of tight junctions. Proinflammatory cytokines and reperfusion increase the expression of cell adhesion molecules and increase immune cell transmigration. Immune cell transmigration could be reduced with anti-cell adhesion molecule antibodies, further validating the model for studying neuroimmune interactions and for conducting high-throughput screening of therapeutic targets that modulate immune cell transmigration into the brain.