Immunity in Rodent Models of Stress

Chronic stress is a major risk factor for several psychiatric disorders, including major depressive disorder and posttraumatic stress disorder. This review synthesizes rodent-based findings showing that stress modifies immune function in the central nervous system (e.g., microglia), the neurovascular unit, and the peripheral circulation. Stress paradigms such as chronic social defeat stress or chronic variable stress induce morphological and transcriptomic changes in microglia, disrupt blood-brain barrier integrity, and mobilize immune cells (e.g., monocytes, neutrophils). These cells, in turn, secrete proinflammatory mediators, including interleukin 6 and matrix metalloproteinase 8, which can penetrate limbic brain regions and contribute to behavioral changes. Integrating next-generation molecular insights with refined behavioral models, particularly those that capture sex-related differences, holds promise for advancing personalized strategies to prevent and treat stress-related disorders.