Brain homeostasis is maintained by "danger" signals stimulating a supportive immune response within the brain's borders.

An organism's behavior is determined by the way it senses and perceives the surrounding environment, and by its responses to these stimuli. The major factors known to affect the behavioral response to an event are genetic background, environmental factors, and past experiences, and their imprinting on the relevant brain circuits. Recently, circulating immune cells were introduced as novel players into this system. It was proposed that the brain and circulating immune cells engage in a continuous dialogue that takes place within the brain's territory, though outside the parenchyma (occurring within the brain's borders - the choroid plexi, the brain meninges and the cerebrospinal fluid (CSF)). The cytokines secreted by activated leukocytes residing at the borders were shown to affect neurotrophic factors production within the parenchyma. Here, we suggest that such a dialogue is stimulated at the brain's borders, upon need, by a "danger" signal that originates in the parenchyma in response to any destabilizing event, and discuss the potential role of reactive oxygen species (ROS) in transmitting this signal. Accordingly, a failure to restore balance is likely to lead to aberrant responses to subsequent events. This view thus supports the contention that circulating immune cells are required to maintain the brain's balanced activity and suggests a novel mechanism whereby the surveying immune cells are sensing the brain's status and needs.