Microglia: dismantling and rebuilding circuits after acute neurological injury

Abstract

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.

Figure 1

(A) Ramified microglia in healthy rat cortex, following brain-injury microglia morphology rapidly changes (A–E). (B) Hyper-ramified, bushy microglia. (C) Activated microglia with fewer processes than either ramified form. (D) Fully activated microglia/infiltrating macrophages have no processes. (E) Rod microglia, this morphology has thin soma and polarized processes.