Citations

Abstract Introduction Colony stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy is an early onset neurodegenerative disease characterized by microglial deficits, abnormal glial responses, white matter pathology, and severe motor and cognitive decline. Methods At 8 months, mice lacking two copies of the Csf1r gene Fms-intronic regulatory element (FIRE) recapitulate some of the brain pathological features of CSF1R-related leukoencephalopathy, namely the deficits in microglia, astrogliosis, and demyelination. Of note, we detected deficits in lymphatic vasculature and altered macrophage activation in the meninges of Csf1rΔFIRE/ΔFIRE mice by flow, prior to the appearance of brain gliosis, neuronal dystrophy, and fine motor impairment. Results Eliminating the remainder CSF1R-expressing innate immune cells, including border-associated macrophages (BAMs), with PLX5622 at 2 months reshaped the immune crosstalk at the meningeal dura and restored lymphatic vascular expansion in Csf1rΔFIRE/ΔFIRE mice Conclusion Ongoing experiments in the lab will clarify the exact mechanisms through which dysfunctional innate immunity at the brain-meningeal interface and lack of meningeal lymphatic vasculature contribute to the development of brain pathology and impaired motor behavior in this model of CSF1R-related leukoencephalopathy. This work has unveiled novel molecular insights involving the meningeal lymphatic system that might be of therapeutic relevance to canonical central nervous system white matter diseases. Funding Source n/a Topic Categories Neuroimmunology (NEUR)

ABSTRACT Microglia as immune cells of the central nervous system (CNS) play significant roles not only in pathology but also in physiology, such as shaping of the CNS during development and its proper maintenance in maturity. Emerging research is showing a close association between microglia and the neurovasculature that is critical for brain energy supply. In this review, we summarize the current literature on microglial interaction with the vascular system in the normal and diseased brain. First, we highlight data that indicate interesting potential involvement of microglia in developmental angiogenesis. Then we discuss the evidence for microglial participation with the vasculature in neuropathologies from brain tumors to acute injuries such as ischemic stroke to chronic neurodegenerative conditions. We conclude by suggesting future areas of research to advance the field in light of current technical progress and outstanding questions. © 2018 Wiley Periodicals, Inc. Develop Neurobiol 78: 604–617, 2018