In traumatic brain injury (TBI), the initial injury phase is followed by a secondary phase that contributes to neurodegeneration, yet the mechanisms leading to neuropathology in vivo remain to be elucidated. To address this question, we developed a Drosophila head-specific model for TBI termed Drosophila Closed Head Injury (dCHI), where well-controlled, nonpenetrating strikes are delivered to the head of unanesthetized flies. This assay recapitulates many TBI phenotypes, including increased mortality, impaired motor control, fragmented sleep, and increased neuronal cell death. TBI results in significant changes in the transcriptome, including up-regulation of genes encoding antimicrobial peptides (AMPs). To test the in vivo functional role of these changes, we examined TBI-dependent behavior and lethality in mutants of the master immune regulator NF-κB, important for AMP induction, and found that while sleep and motor function effects were reduced, lethality effects were enhanced. Similarly, loss of most AMP classes also renders flies susceptible to lethal TBI effects. These studies validate a new Drosophila TBI model and identify immune pathways as in vivo mediators of TBI effects.

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While droplet microfluidics is becoming an effective tool for biomedical research, sensitive detection of droplet content is still challenging, especially for multiplexed analytes compartmentalized within ultrasmall droplets down to picoliter volumes. To enable such measurements, we demonstrate a silicon-based integrated microfluidic platform for multiplexed analysis of neurochemicals in picoliter droplets via nanoelectrospray ionization (nESI)-mass spectrometry (MS). An integrated silicon microfluidic chip comprising downscaled 7 μm-radius channels, a compact T-junction for droplet generation, and an integrated nESI emitter tip is used for segmentation of analytes into picoliter compartments and their efficient delivery for subsequent MS detection. The developed system demonstrates effective detection of multiple neurochemicals encapsulated within oil-isolated plugs down to low picoliter volumes. Quantitative measurements for each neurochemical demonstrate limits of detection at the attomole level. Such results are promising for applications involving label-free and small-volume detection for monitoring a range of brain chemicals.

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