NEUROIMMUNE CROSSTALK IN BRAIN HEALTH AND DISEASE: EMERGING ROLES AND THERAPEUTIC TARGETS

The brain and immune system talk constantly, swapping chemical whispers and electrical nudges that decide whether to stay sharp, forget, or fall apart. Here, we piece together the conversation: antigens seep from cerebrospinal fluid into dural sinuses where quiet T cells peek without triggering chaos; microglia slip lysosomal enzymes into neurons to keep lipid clocks ticking, but if the exchange stalls GM2 ganglioside piles up and lights the fuse of neurodegeneration; astrocytes ship cholesterol to remyelinating oligodendrocytes, yet in male mice the same cargo becomes a roadblock unless luteolin opens the efflux hatch. Danger signals ATP, HMGB1, misfolded proteins flip purinergic and TLR switches that weld NLRP3 inflammasomes, releasing IL-1β waves that travel from cortex to coronary arteries, linking stroke risk to mood dips. When the chatter derails, autism brains show IL-17 graffiti, lupus neutrophils spew NETs that shred the blood–brain barrier, Parkinson’s mitochondria leak ROS that become microglia, and depressed hippocampi drowned in kynurenine. Vagus-nerve stimulation, SIRT1 boosters, NET-cutting DNase I, CGRP silencers, and programmable bioelectronic implants can reduce or increase the volume, but human trials remain small, short, and noisy.