Mechanisms and potential therapeutic applications of microglial activation after brain injury

Abstract

As the resident immune cells of the central nervous system, microglia rapidly respond to brain insults, including stroke and traumatic brain injury. Microglial activation plays a major role in neuronal cell damage and death by releasing a variety of inflammatory and neurotoxic mediators. Their activation is an early response that may exacerbate brain injury and many other stressors, especially in the acute stages, but are also essential to brain recovery and repair. The full range of microglial activities is still not completely understood, but there is accumulating knowledge about their role following brain injury. We review recent progress related to the deleterious and beneficial effects of microglia in the setting of acute neurological insults and the current literature surrounding pharmacological interventions for intervention.

Keywords: Brain injury; Inflammation; Microglia; Neurotoxic mediator.

Figure 1

Microglial activation in brain injury. Microglia are activated by brain injury such as ischemic stroke and traumatic brain injury, which affect the polarization status of the cell. In brain injury, resting microglia (M) can be polarized to the M1 phenotype, or alternatively to the antiinflammatory, pro‐phagocytic M2 phenotype by the some of factors shown in the gray boxes. M1 microglia take part in the neuronal damage by elaborating pro‐inflammatory molecules, whereas M2 microglia promote neuronal protection, and through phagocytic functions, set the stage for recovery and repair. While not extensively studied in brain injury, CD40 leads to the M1 phenotype, whereas CD45 turns this “off.”