Microglial physiopathology: how to explain the dual role of microglia after acute neural disorders?

Microglia are the resident macrophages of the central nervous system (CNS). In physiological conditions, resting microglia maintain tissue integrity by scanning the entire CNS parenchyma through stochastic and complex movements of their long processes to identify minor tissue alterations. In pathological conditions, over-activated microglia contribute to neuronal damage by releasing harmful substances, including inflammatory cytokines, reactive oxygen species, and proteinases, but they can provide tissue repair by releasing anti-inflammatory cytokines and neurotrophic factors. The reasons for this apparent paradox are unknown. In this paper, we first review the physiological role as well as both detrimental and beneficial actions of microglial during acute CNS disorders. Further, we discuss the possible reasons for this microglial dual role following CNS insults, considering that the final microglial phenotype is a direct consequence of both noxious and beneficial stimuli released into the extracellular space during the pathological insult. The nature of these micro-glial ligands is unknown, but we hypothesize that harmful and beneficial stimuli may be preferentially located at specific anatomical niches along the pathological environment triggering both beneficial and deleterious actions of these glial cells. According to this notion, there are no natural populations of detrimental microglia, but is the pathological environment that determines the final microglial phenotype.