Roles of microglia in brain development, tissue maintenance and repair

Abstract

The emerging roles of microglia are currently being investigated in the healthy and diseased brain with a growing interest in their diverse functions. In recent years, it has been demonstrated that microglia are not only immunocentric, but also neurobiological and can impact neural development and the maintenance of neuronal cell function in both healthy and pathological contexts. In the disease context, there is widespread consensus that microglia are dynamic cells with a potential to contribute to both central nervous system damage and repair. Indeed, a number of studies have found that microenvironmental conditions can selectively modify unique microglia phenotypes and functions. One novel mechanism that has garnered interest involves the regulation of microglial function by microRNAs, which has therapeutic implications such as enhancing microglia-mediated suppression of brain injury and promoting repair following inflammatory injury. Furthermore, recently published articles have identified molecular signatures of myeloid cells, suggesting that microglia are a distinct cell population compared to other cells of myeloid lineage that access the central nervous system under pathological conditions. Thus, new opportunities exist to help distinguish microglia in the brain and permit the study of their unique functions in health and disease.

Neuroimmune Response in Ischemic Preconditioning

“…The cellular response to stroke, particularly the response of immune cells, has been studied extensively and has been recently reviewed in detail [19,75]. Post-ischemic inflammation is characterized by an orderly sequence of events involving the brain, its vessels, the circulating blood, and lymphoid organs [19].…”

“…Insulin-like growth factor 1 and VEGF contribute to postischemic neuronal sprouting and angiogenesis, respectively. Stroke also induces profound changes in the systemic immune response [75]. Within a few hours of the onset of cerebral ischemia, brain-immune system interactions can result in downregulation of systemic immunity, a phenomenon known as stroke-induced immunodepression [76].…”

“…Many of these processes also play a central role in preconditioning-mediated neuroprotection. The kinetics of post-stroke immune reactions are critical in postischemic physiology and the concept of a biphasic or multiphasic response to brain ischemia is now favored [53,68,75,77]. The preconditioning phenomenon has this temporal component built into its structure such that the primary preconditioning stimulus (whether it is brain ischemia, remote ischemia, administration of a TLR agonist, or something else) induces a response that has already evolved considerably toward the Bresolution of inflammation^or Bregeneration and repair^phase.…”

Intracerebral Hemorrhage as an Axonal Tract Injury Disorder with Inflammatory Reactions

“…31) On the other hand, it should be noted that both neutrophils and microglia/macrophages can be either destructive or protective to injured tissues, presumably depending on their polarized phenotypes. 32,33) These cell populations may act in distinct temporal and spatial patterns to affect the integrity of axonal tracts after ICH insults, and our current working hypothesis is depicted in Fig. 3.…”

Correction to: Neuroimmune Response in Ischemic Preconditioning

“…Microglia are CNS-resident immune cells derived from yolk sac macrophages that enter the CNS during early development and maintain themselves as a distinct population from circulating macrophages/monocytes [78][79][80], despite a high overlap in shared expression of many immunohistochemical markers [17,81]. Microglia contribute to the maintenance of brain homeostasis, suggesting a critical role for microglia in the normal physiology of the CNS [56], and pathway analysis of baseline microglial gene expression (from naïve wild-type mouse brain) revealed that the functions most associated with microglia were related to nervous system development [82].…”