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In neurological diseases, the actions of microglia, the resident myeloid cells of the CNS parenchyma, may diverge from, or intersect with, those of recruited monocytes to drive immune-mediated pathology. However, defining the precise roles of each cell type has historically been impeded by the lack of discriminating markers and experimental systems capable of accurately identifying them. Our ability to distinguish microglia from monocytes in neuroinflammation has advanced with single-cell technologies, new markers and drugs that identify and deplete them, respectively. Nevertheless, the focus of individual studies on particular cell types, diseases or experimental approaches has limited our ability to connect phenotype and function more widely and across diverse CNS pathologies. Here, we critically review, tabulate and integrate the disease-specific functions and immune profiles of microglia and monocytes to provide a comprehensive atlas of myeloid responses in viral encephalitis, demyelination, neurodegeneration and ischemic injury. In emphasizing the differential roles of microglia and monocytes in the severe neuroinflammatory disease of viral encephalitis, we connect inflammatory pathways common to equally incapacitating diseases with less severe inflammation. We examine these findings in the context of human studies and highlight the benefits and inherent limitations of animal models that may impede or facilitate clinical translation. This enables us to highlight common and contrasting, non-redundant and often opposing roles of microglia and monocytes in disease that could be targeted therapeutically., (© 2021. The Author(s).)

After lead (Pb) is injected into striated muscle it binds to the sarcolemma of the neuromuscular junction (NMJ) and crosses into the terminal axons of motor neurons. To find out whether this intra-axonal accumulation of Pb is due to active transport or to diffusion down a concentration gradient, Pb uptake into motor axons of mice was studied at active and inactive NMJs. Twenty-four hours after sciatic nerve crush, 0.1 ml of 5% lead nitrate was injected into the tibialis anterior muscle and 30 min later the location of Pb was sought with electron microscopy and X-ray elemental analysis. A greatly reduced amount of Pb entered the axons after nerve crush compared to non-nerve crush animals, indicating that an active NMJ is required for intra-axonal Pb accumulation. To test if Pb could be entering the axon via recycling vesicles, botulinum toxin (BoTx) was injected into the muscle 24 h before Pb injection. There was no difference in intra-axonal Pb uptake in control and BoTx-injected animals, indicating that Pb is unlikely to use recycled vesicles to enter the axon.