Mast cells (MCs) are found abundantly in the brain and the meninges and play a complex role in neuroinflammatory diseases, such as stroke and multiple sclerosis. Here, we show that MC-deficient Kit/Kit mice display increased neurodegeneration in the lesion area after brain trauma. Furthermore, MC-deficient mice display significantly more brain inflammation, namely an increased presence of macrophages/microglia, as well as dramatically increased T-cell infiltration at days 4 and 14 after injury, combined with increased astrogliosis at day 14 following injury. The number of proliferating Ki67 macrophages/microglia and astrocytes around the lesion area is more than doubled in these MC-deficient mice. In parallel, MC-deficient Kit mice display increased presence of macrophages/microglia at day 4, and persistent astrogliosis at day 4 and 14 after brain trauma. Further analysis of mice deficient in one of the most relevant MC proteases, i.e., mouse mast cell protease 4 (mMCP-4), revealed that astrogliosis and T-cell infiltration are significantly increased in mMCP-4-knockout mice. Finally, treatment with an inhibitor of mMCP-4 significantly increased macrophage/microglia numbers and astrogliosis. These data suggest that MCs exert protective functions after trauma, at least in part via mMCP-4, by suppressing exacerbated inflammation via their proteases.

In the healthy mammalian CNS, mast cells (MCs) are thought to be located mostly in the thalamus. In this study, we have systematically assessed the presence of MCs in the hippocampal formation (HF) and in the thalamus of normal male and female B10.PL mice. Giemsa+ and Toluidine Blue+ MCs were detected by histomorphometric analyses at perivascular and intraparenchymal sites of both the hippocampus and the entorhinal cortex. We found a mean number of 4.4 MCs in the HF of female and 3.3 MCs in male B10.PL mice. In contrast to the HF, no MCs were present in the thalamus of these mice. Notably, all HF-MCs showed immunoreactivity for Kit, the receptor for the MC growth and maturation factor SCF, as assessed by FITC–avidin/Kit double labelling. We demonstrate that the majority of brain MCs is found in the hippocampus and entorhinal cortex of B10.PL mice, though the total number of MCs is small compared to other mouse strains or rats. The presence of most brain MCs in the HF of B10.PL mice suggests a potential role of MCs in hippocampal physiology and pathology.