Microglia: dismantling and rebuilding circuits after acute neurological injury (original) (raw)

2014, Metabolic Brain Disease

The brain is comprised of neurons and its support system including astrocytes, glial cells and microglia, thereby forming neurovascular units. Neurons require support from glial cells to establish and maintain functional circuits, but microglia are often overlooked. Microglia function as the immune cell of the central nervous system, acting to monitor the microenvironment for changes in signaling, pathogens and injury. More recently, other functional roles for microglia within the healthy brain have been identified, including regulating synapse formation, elimination and function. This review aims to highlight and discuss these alternate microglial roles in the healthy and in contrast, diseased brain with a focus on two acute neurological diseases, traumatic brain injury and epilepsy. In these conditions, microglial roles in synaptic stripping and stabilization as part of neuronal:glial interactions may position them as mediators of the transition between injury-induced circuit dismantling and subsequent reorganization. Increased understanding of microglia roles could identify therapeutic targets to mitigate the consequences of neurological disease. Microglia: Amoeboid to ramified and back again Microglial morphology has long been interpreted to follow function, with surface antigens changing dependent on the stimulus for activation and the role required to play in the brain. This simplistic view is now being challenged, with data collected over the previous decades indicating alternate roles for microglia, particularly in the uninjured brain. During development of the brain, microglial precursors undergo three developmental milestones toward becoming fully integrated microglia. Microglia proliferate and migrate to populate different central nervous system (CNS) regions, and then differentiate from an amoeboidlike form into their ramified morphology. Within the non-pathological brain, ramified microglia constantly survey the microenvironment by movement of their fine processes, sampling the surface of cells and interstitial fluid in their immediate vicinity [1, 2] and