Role of infiltrating monocytes/macrophages in acute and chronic neuroinflammation: Effects on cognition, learning and affective behaviour.

Peripheral macrophages have limited capacity to gain access to the brain parenchyma under normal physiological conditions. However, accumulating evidence indicates that significant trafficking to the central nervous systems occurs in response to injury or infection and is also apparent under chronic neuroinflammatory conditions. The role of infiltrating macrophages in neuronal function is unclear and confounded by the similarity in morphology and phenotype adopted by both activated macrophages and microglia. Furthermore, the ability of macrophages/microglia to adopt both pro- and anti-inflammatory activation states, along with the fact that these cells display heterogenous expression of molecules associated with both states, has made it difficult to discover their impact upon neuronal injury and cognitive processes. The ability of macrophages to exert a neuroprotective role is influenced by the microenvironment they encounter upon tissue invasion. Upon encountering an inflammatory microenvironment, macrophage polarisation is driven towards a pro-inflammatory (M1) phenotype, a state associated with reduced capacity for restorative processes such as the removal of debris, and enhanced production of pro-inflammatory mediators such as TNFα, IL-1β and NADPH oxidase. Prolonged production of these inflammatory mediators has been shown to affect neuronal function and health. Thus, macrophage polarisation may be dictated by the inflammatory queues these cells are exposed to upon migration and their subsequent impact on neuronal function may be determined by their ability to resolve the underlying inflammation.