Microglia mediate chronic neuroinflammation following central nervous system (CNS) disease or injury, and in doing so, damage the local brain environment by impairing recovery and contributing to disease processes. Microglia are critically dependent on signaling through the colony-stimulating factor 1 receptor (CSF1R) and can be eliminated via administration of CSF1R inhibitors. Resolving chronic neuroinflammation represents a universal goal for CNS disorders, but long-term microglial elimination may not be amenable to clinical use. Notably, withdrawal of CSF1R inhibitors stimulates new microglia to fully repopulate the CNS, affording an opportunity to renew this cellular compartment. To that end, we have explored the effects of acute microglial elimination, followed by microglial repopulation, in a mouse model of extensive neuronal loss. Neuronal loss leads to a prolonged neuroinflammatory response, characterized by the presence of swollen microglia expressing CD68 and CD45, as well as elevated levels of cytokines, chemokines, complement, and other inflammatory signals. These collective responses are largely resolved by microglial repopulation. Furthermore, microglial repopulation promotes functional recovery in mice, with elevated plus maze performance matching that of uninjured mice, despite the loss of 80% of hippocampal neurons. Analyses of synaptic surrogates revealed increases in PSD95 and synaptophysin puncta with microglial repopulation, suggesting that these cells sculpt and regulate the synaptic landscape. Thus, our results show that short-term microglial elimination followed by repopulation may represent a clinically feasible and novel approach to resolve neuroinflammatory events and promote brain recovery.

Meningiomas have been implicated as the most common primary intracranial tumor to contain tumor-to-tumor metastasis. In the following two case reports, we describe cases of adenocarcinoma and breast carcinoma that metastasized into an intracranial meningioma. The first patient was a 64-year-old man presenting to the emergency department with seizures and loss of consciousness. After a left frontal mass resection, pathology reported a heterogeneous mass consisting of a meningioma and a metastatic adenocarcinoma component. The second patient was a 63-year-old woman presenting with significant vision problems and unstable gait. After a right frontal mass resection, pathology reported a heterogeneous mass consisting of a meningioma and a metastatic breast carcinoma component. Possible explanations for the development of the tumor-to-tumor metastasis are described.