Why Your Brain Fog Won't Lift: The Six Mechanisms of Cognitive Dysfunction in Chronic Illness, and Why Standard Interventions Keep Failing — Mechanism Five: Mast Cell Activation in the Central Nervous System

Mast cells are present in the central nervous system, particularly in the meninges, the hypothalamus, the thalamus, the median eminence, and along cerebral vessels. Their density is lower than in peripheral tissues, but their activation has disproportionate effects on local function because of the privileged nature of the brain compartment and the proximity of mast cells to neural structures that integrate widespread function. Central mast cells release the same mediators as peripheral mast cells (histamine, tryptase, prostaglandins, leukotrienes, cytokines). The mediators act locally on neurons, astrocytes, microglia, and the blood brain barrier. Histamine in the brain acts on H1, H2, H3, and H4 receptors with varying tissue distributions. H1 activation produces arousal effects but also contributes to neuroinflammation when sustained. H3 activation modulates the release of other neurotransmitters and is involved in wakefulness regulation. The mast cell mediator profile generates a characteristic combination of cognitive symptoms (brain fog, difficulty concentrating, mental fatigue), arousal symptoms (anxiety, hypervigilance, insomnia), and sensory symptoms (light sensitivity, sound sensitivity, smell sensitivity). Mast cells in the brain are activated by many of the same triggers as peripheral mast cells, with the addition of triggers that are specific to the central nervous s