The concept of microglia in relation to central nervous system disease and regeneration.

In a relatively short period of time, the microglial cell has gone from a strongly contested component of the central nervous system (CNS), to being recognised as one of the main players in the response to brain injury. Microglia are thought to arise from cells of haematopoietic origin, and enter the brain in response to naturally occurring cell death. As a result, the microglial cell is the representative of the immune system within the brain. However, the main role of microglia in the adult CNS is to respond to disruption of the homeostasis of the brain, whether that disruption comes from direct damage to neurons, neuronal degeneration or through disease. In this paper we investigate three main causes of cell death in the CNS: inherited degeneration, traumatic lesions and human diseases, and the microglial response to each. Then we examine the mechanisms by which microglia control their surroundings and the methods employed by these cells to instigate neuronal death. Recent observations suggest that under no conditions where neurons are dying or regrowing are microglia not involved, and control of microglia is likely to be just as important in regeneration as providing a favourable environment for neurons to grow. In short, microglia cannot be seen merely as cells of a certain type within the brain, possessing certain functions, but instead must be regarded as a concept that shapes the approaches taken to nervous system development, cell death, disease and trauma, and nervous system regeneration.