Neuroinflammation

Neuroinflammation is chronic low-grade immune activation within the central nervous system, driven primarily by microglia — the brain's resident immune cells. Unlike acute inflammation, which is protective and self-limiting, neuroinflammation is persistent, maladaptive, and increasingly implicated in the pathophysiology of depression, cognitive decline, and neurodegenerative disease.

Microglia are not merely defensive sentinels. They actively sculpt synaptic connectivity during development and modulate neural plasticity throughout life. When chronically activated — by peripheral cytokines, stress hormones, or neuronal damage — they shift from a regulatory to a pro-inflammatory phenotype, releasing reactive oxygen species and cytokines that impair neurogenesis and synaptic function. The boundary between protective immune surveillance and destructive neuroinflammation is not a fixed threshold but a dynamical regime.

The concept of microglial priming is central: once activated, microglia enter a sensitized state in which subsequent inflammatory triggers produce exaggerated responses. This priming mechanism explains why early-life infection or trauma can produce lasting vulnerability to later stressors — the immune memory of the brain outlasts the event that created it.