The Yin and Yang of Microglia

Abstract

Microglia, the resident immune cells of the mammalian central nervous system (CNS), play a pivotal role in both physiological and pathological conditions such as the restoration of CNS integrity and the progression of neurodegenerative disorders. Extensive data have been published that describe neuroinflammation by microglial activation to have detrimental consequences on the developing and mature brain. On the other hand, a properly directed and limited inflammatory response is known to be a natural healing process after an insult in several other tissues. Thus, it is not surprising that research results illustrating benefits of neuroinflammation have been emerging over the past decade. Inflammation-mediated benefits for CNS outcomes include mechanisms such as neuroprotection, mobilization of neural precursors for repair, remyelination and axonal regeneration. Here, we review data that highlight the dual aspects of microglia with a focus on the developing brain, i.e. as aggressors potentiating damage and as helpers in the recovery process following CNS damage.

Inflammation‐induced sensitization of the brain in term infants

“…109 However, the pro-inflammatory response may not be entirely harmful; some reactions are helpful for tissue repair, and hypothermia is likely to inhibit both beneficial and detrimental inflammatory responses. [110][111][112] A recent study investigated the effects of therapeutic hypothermia on the peripheral immune response, within 72h of birth, in 65 infants with neonatal encephalopathy. 113 Hypothermic infants had lower white blood cell counts and lower absolute neutrophil and lymphocyte counts than normothermic infants.…”

Mesenchymal stem cells as a treatment for neonatal ischemic brain damage

“…Microglia are the resident macrophages of the central nervous system. They are bone marrow-derived monocytes that migrate to the brain during development and differentiate locally into resident microglia (43,66). Upon a stressor or injury, both activation of resident brain microglia and recruitment of monocytes from the periphery contribute to the increase in the number of microglia/macrophages in the injured area (43,65).…”

“…During brain injury, microglia undergo a rapid shift in their effector program and become activated. Depending on the surrounding conditions, microglia shift their activity state to become "classically activated" M1 microglia or "alternatively activated" M2 microglia (66,67). M1 microglia are a major source of proinflammatory cytokines, oxidative metabolites, and other neurotoxins and thereby contribute to ensuing damage, whereas M2-activated microglia can be neuroprotective and can promote repair by releasing growth factors like IL10, insulin growth factor-1, and transforming growth factor-β and modulating the immune response (68).…”

Nanomedicine in cerebral palsy

“…[24][25][26][27][28] However, the microglial/macrophage response may depend on the type (infection/inflammation versus hypoxic ischemia) and the timing of injury (acute versus chronic). Suppressing the immediate microglial response after an hypoxic-ischemic insult in a neonatal stroke rat model has been shown to be deleterious.…”

“…29 However, a proinflammatory activation of these cells can result in an exaggerated, ongoing inflammatory response that persists long after the injury, with formation of free radicals, excitotoxic metabolites, and proinflammatory cytokines, leading to diffuse white and grey matter injury as seen in CP. [26][27][28] In severe inflammation, astrocytes that normally participate in the protection of neurons and in preventing oxidative injury, are unable to maintain their neuroprotective role. 30 An increased number of activated microglia have been noted along the white matter tract in autopsy specimens of patients with PVL.…”