Neurovascular unit on a chip: implications for translational applications

The blood–brain barrier (BBB) dynamically controls exchange between the brain and the body, but this interaction cannot be studied directly in the intact human brain or suffi ciently represented by animal models. Most existing in vitro BBB models do not include neurons and glia with other BBB elements and do not adequately predict drug effi cacy and toxicity. Under the National Institutes of Health Microtissue Initiative, we are developing a threedimensional, multicompartment, organotypic microphysiological system representative of a neurovascular unit of the brain. The neurovascular unit system will serve as a model to study interactions between the central nervous system neurons and the cerebral spinal fl uid (CSF) compartment, all coupled to a realistic blood-surrogate supply and venous return system that also incorporates circulating immune cells and the choroid plexus. Hence all three critical brain barriers will be recapitulated: blood–brain, brain–CSF, and blood–CSF. Primary and stem cell-derived human cells will interact with a variety of agents to produce critical chemical communications across the BBB and between brain regions. Cytomegalovirus, a common herpesvirus, will be used as an initial model of infections regulated by the BBB. This novel technological platform, which combines innovative microfl uidics, cell culture, analytical instruments, bioinformatics, control theory, neuroscience, and drug discovery, will replicate chemical communication, molecular traffi cking, and infl ammation in the brain. The platform will enable targeted and clinically relevant nutritional and pharmacologic interventions for or prevention of such chronic diseases as obesity and acute injury such as stroke, and will uncover potential adverse eff ects of drugs. If successful, this project will produce clinically useful technologies and reveal new insights into how the brain receives, modifi es, and is aff ected by drugs, other neurotropic agents, and diseases

Summing the strokes: energy economy in northern elephant seals during large-scale foraging migrations

BACKGROUND: The energy requirements of free-ranging marine mammals are challenging to measure due to cryptic and far-ranging feeding habits, but are important to quantify given the potential impacts of high-level predators on ecosystems. Given their large body size and carnivorous lifestyle, we would predict that northern elephant seals (Mirounga angustirostris) have elevated field metabolic rates (FMRs) that require high prey intake rates, especially during pregnancy. Disturbance associated with climate change or human activity is predicted to further elevate energy requirements due to an increase in locomotor costs required to accommodate a reduction in prey or time available to forage. In this study, we determined the FMRs, total energy requirements, and energy budgets of adult, female northern elephant seals. We also examined the impact of increased locomotor costs on foraging success in this species. RESULTS: Body size, time spent at sea and reproductive status strongly influenced FMR. During the short foraging migration, FMR averaged 90.1 (SE = 1.7) kJ kg(−1)d(−1) – only 36 % greater than predicted basal metabolic rate. During the long migration, when seals were pregnant, FMRs averaged 69.4 (±3.0) kJ kg(−1)d(−1) – values approaching those predicted to be necessary to support basal metabolism in mammals of this size. Low FMRs in pregnant seals were driven by hypometabolism coupled with a positive feedback loop between improving body condition and reduced flipper stroking frequency. In contrast, three additional seals carrying large, non-streamlined instrumentation saw a four-fold increase in energy partitioned toward locomotion, resulting in elevated FMRs and only half the mass gain of normally-swimming study animals. CONCLUSIONS: These results highlight the importance of keeping locomotion costs low for successful foraging in this species. In preparation for lactation and two fasting periods with high demands on energy reserves, migrating elephant seals utilize an economical foraging strategy whereby energy savings from reduced locomotion costs are shuttled towards somatic growth and fetal gestation. Remarkably, the energy requirements of this species, particularly during pregnancy, are 70–80 % lower than expected for mammalian carnivores, approaching or even falling below values predicted to be necessary to support basal metabolism in mammals of this size. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40462-015-0049-2) contains supplementary material, which is available to authorized users