A new editorial and synthesis argues that neuroimmune signaling at the neurovascular unit creates a shared machinery connecting recurrent peripheral inflammation to central outcomes across disorders. The piece frames “neuroimmune buffering reserve” through CLDN5 and microglia-centered mechanisms, aiming to unify how systemic inflammatory episodes shape brain vulnerability and psychiatric-neurologic phenotypes. For translational teams, the emphasis on interface-specific biology may help focus biomarker development and patient stratification strategies—particularly for conditions where conventional compartmentalization between neurological and immune drivers has complicated therapeutic targeting.