A Microfluidic Framework for Neuroprotective Compound Triage Across Ischemia and Neurodegeneration.

Microfluidic systems are increasingly used in neuroprotection research, but their clearest value may be to show why candidate compounds fail before costly downstream models. This critical framework review examines CNS-relevant microfluidic studies through a within-program triage logic linking chemistry-aware prescreening, blood-brain barrier/neurovascular unit (BBB/NVU) filtering, and timed validation in neuronal ischemia/reperfusion models, and treats non-CNS organ-on-a-chip and analytical microfluidic studies as engineering analogies only. The available evidence most strongly supports BBB/NVU chips as exposure- and safety-aware filters and compartmentalized neuronal oxygen-glucose deprivation platforms as timing-sensitive validation tools; droplet microfluidics contributes mainly upstream through dense dose mapping, aggregation assays and counterscreens for assay interference. A compound-centered reading also suggests that apparent activity often fails for distinct reasons, including timing mismatch, poor solubility, surface adsorption, optical artifact, inadequate multicellular context, or loss of efficacy under transport-aware testing. Taken together, the literature supports a cautious, within-program triage logic in which microfluidics is used not as a universal disease model, but as an operational framework for exposing transport, barrier, timing and assay liabilities early in neuroprotective discovery.