Microglial priming and enhanced reactivity to secondary insult in aging, and traumatic CNS injury, and neurodegenerative disease

• Published in: Neuropharmacology Vol. 96; no. Pt A; pp. 29 - 41
• Main Authors: Norden, Diana M., Muccigrosso, Megan M., Godbout, Jonathan P.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2015
• Subjects: Aging; Astrocytes - immunology; Brain Injuries - complications; Brain Injuries - immunology; Craniocerebral Trauma - complications; Craniocerebral Trauma - immunology; Encephalitis - complications; Encephalitis - immunology; Humans; Illness Behavior - physiology; Inflammation; Inflammation Mediators - immunology; Male; Microglia; Microglia - immunology; Neurodegenerative disease; Neurodegenerative Diseases - complications; Neurodegenerative Diseases - immunology; Neuronal Plasticity; Priming; Traumatic brain injury; Aging; Priming; Neurodegenerative disease; Inflammation; Traumatic brain injury; Microglia
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2014.10.028

Glia of the central nervous system (CNS) help to maintain homeostasis in the brain and support efficient neuronal function. Microglia are innate immune cells of the brain that mediate responses to pathogens and injury. They have key roles in phagocytic clearing, surveying the local microenvironment and propagating inflammatory signals. An interruption in homeostasis induces a cascade of conserved adaptive responses in glia. This response involves biochemical, physiological and morphological changes and is associated with the production of cytokines and secondary mediators that influence synaptic plasticity, cognition and behavior. This reorganization of host priorities represents a beneficial response that is normally adaptive but may become maladaptive when the profile of microglia is compromised. For instance, microglia can develop a primed or pro-inflammatory mRNA, protein and morphological profile with aging, traumatic brain injury and neurodegenerative disease. As a result, primed microglia exhibit an exaggerated inflammatory response to secondary and sub-threshold challenges. Consequences of exaggerated inflammatory responses by microglia include the development of cognitive deficits, impaired synaptic plasticity and accelerated neurodegeneration. Moreover, impairments in regulatory systems in these circumstances may make microglia more resistant to negative feedback and important functions of glia can become compromised and dysfunctional. Overall, the purpose of this review is to discuss key concepts of microglial priming and immune-reactivity in the context of aging, traumatic CNS injury and neurodegenerative disease. This article is part of a Special Issue entitled ‘Neuroimmunology and Synaptic Function’. •Discuss basics of glial biology and heightened inflammatory state of microglia.•“Microglial priming” in aging, traumatic brain injury and neurodegenerative disease.•A consequence of priming is increased immune-reactivity to secondary insult.•Relevance of amplified response to secondary insult within these models.•Evidence of microglial priming as a trigger for neuropsychiatric problems.