Localization of mast cells in human brain tissue: Implications for neuropsychiatric symptoms in COVID-19

To the Editor: Mast cells (MCs) are tissue-resident immune cells that release both pro- and anti-inflammatory mediators.1 Mast cell disorders, such as systemic mastocytosis (a rare clonal disorder) and mast cell activation syndromes (MCAS) are associated with high rates of neuropsychiatric symptoms, including depression and cognitive dysfunction.2 However, little attention has been paid to the location of MCs within the brain as a potential contributor to these manifestations. This gap is particularly striking given the public health burden of COVID-19 and long COVID, in which MC activation-related symptoms have been described.3 These observations raise the question of whether MCs localize within the brain parenchyma and release mediators that could contribute to neuropsychiatric symptoms. Studies in rodents have identified MCs in the brain and meninges where they influence neuroinflammation, cerebrospinal fluid flow, and behavior.4–7 More recent findings point to their presence at the dura-brain interface and around blood vessels, raising the possibility that MCs contribute to vascular regulation.8,9 Mast cells have also been described in the human central nervous system, particularly in perivascular regions, leptomeninges, and specialized neurovascular interface structures such as the area postrema and hypothalamic infundibulum.10–14 However, systematic data on the presence and localization of MCs in human brain tissue remain limited, and prior studies using non-MC-specific staining techniques may have underestimated their presence or density.