Microglia in diseases of the central nervous system

Abstract

Microglia (MG) are enigmatic cells of the central nervous system (CNS). MG are morphologically, antigenically and functionally flexible, and have the potential for mobility and proliferation. MG are professional antigen-presenting cells and constitute part of the local CNS innate immune system, communicating with other immune cells via chemokines, cytokines and growth factors. MG contain several antigenic and functional markers similar to macrophages and dendritic cells (DCs), but also present several differences from DCs. The exact role(s) played by MG in the normal human CNS is the topic of lively debate. MG participate in many reactive processes in the CNS and are therefore an integral part of lesions in a variety of pathologic conditions. It is thought that MG may exacerbate diverse neurological conditions, including viral encephalitis, AIDS, Multiple Sclerosis (MS) and Alzheimer's disease. A recurrent theme is the perpetuation by MG of pathological cycles of monocyte recruitment, activation and cytopathic secretions, and/or auto antigen presentation.

The Ca2+-Activated K+ChannelKCNN4/KCa3.1 Contributes to Microglia Activation and Nitric Oxide-Dependent Neurodegeneration

“…Importantly, there was no evidence of drug toxicity with even the highest doses of TRAM-34, i.e., there were no seizures or changes in feeding, activity, or behavior. The outcome of microglia activation can be complex and determined primarily by the factors they produce (for review, see Zielasek and Hartung, 1996;Nelson et al, 2002;Vilhardt, 2005). Together with our in vitro results showing an involvement of KCa3.1 channels in microglia iNOS induction, nitric oxide production, and p38 MAPK activation, the in vivo results suggest that KCa3.1 blockade likely acts by reducing production and/or secretion of soluble neurotoxic molecules in the retina.…”

“…Because some microglia functions can exacerbate CNS disorders, including stroke, traumatic brain injury, multiple sclerosis, and several retinal diseases (for review, see Minagar et al, 2002;Nelson et al, 2002;Pocock et al, 2002), controlling their activation might ameliorate immune-mediated CNS disorders. We present evidence that the Ca 2ϩ -dependent K ϩ channel KCa3.1 (KCNN4/ IK1/SK4) is a potential therapeutic target for inflammationmediated neurotoxicity in the CNS.…”

Neuritic Beading Induced by Activated Microglia Is an Early Feature of Neuronal Dysfunction Toward Neuronal Death by Inhibition of Mitochondrial Respiration and Axonal Transport

“…Central nervous system inflammation including microglial activation likely contributes to the neurotoxicity observed in neurodegenerative diseases such as Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, and multiple sclerosis (1)(2)(3)(4)(5)(6)(7). Additionally, excitotoxicity might lead to neuronal damage in these neurodegenerative diseases (8,9).…”

A Novel Immune-Based Therapy for Stroke Induces Neuroprotection and Supports Neurogenesis

“…Postinjury immune response has often been perceived as part of the detrimental cascade that causes neuronal death and impairs neurogenesis. [23][24][25] Consequently, a number of antiinflammatory agents have been tested in animal models of stroke, with the goal of limiting the recruitment and activation of inflammatory cells. 24 This approach was indeed found to reduce infarct size and neurological deficits if applied within a few hours of ischemic onset.…”

“…[23][24][25] Consequently, a number of antiinflammatory agents have been tested in animal models of stroke, with the goal of limiting the recruitment and activation of inflammatory cells. 24 This approach was indeed found to reduce infarct size and neurological deficits if applied within a few hours of ischemic onset. However, a controlled clinical trial with the anti-inflammatory corticosteroid methylprednisolone resulted in an unexpected increase in short-term mortality.…”