Experimental autoimmune encephalomyelitis repressed by microglial paralysis

Heppner, Frank L.; Greter, Melanie; Marino, Denis; Falsig, Jeppe; Raivich, Gennadij; Hövelmeyer, Nadine; Waisman, Ari; Rülicke, Thomas; Prinz, Marco; Priller, Josef; Becher, Burkhard; Aguzzi, Adriano

doi:10.1038/nm1177

Cited by 677 publications

(571 citation statements)

References 46 publications

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“…A similar beneficial effect of microglia in stroke was reported in a study where there was a 60 % increase in infarct size by selective elimination of microglia, which the effect was reversed by repopulating the cells [65]. In contrast, microglia ablation was either protective or had no effect in models of other neurodegenerative diseases, including Alzheimer's disease [66], amyotrophic lateral sclerosis [67], and experimental autoimmune encephalomyelitis [68].…”

Section: Microgliasupporting

confidence: 64%

Microglia and Monocyte-Derived Macrophages in Stroke

2016

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Historically, the brain has been considered an immune-privileged organ separated from the peripheral immune system by the blood-brain barrier. However, immune responses do occur in the brain in neurological conditions in which the integrity of the blood-brain barrier is compromised, exposing the brain to peripheral antigens and endogenous danger signals. While most of the associated pathological processes occur in the central nervous system, it is now clear that peripheral immune cells, especially mononuclear phagocytes, that infiltrate into the injury site play a key role in modulating the progression of primary brain injury development. As inflammation is a necessary and critical component for the subsequent injury resolution process, understanding the contribution of mononuclear phagocytes on the regulation of inflammatory responses may provide novel approaches for potential therapies. Furthermore, predisposed comorbid conditions at the time of stroke cause the alteration of stroke-induced immune and inflammatory responses and subsequently influence stroke outcome. In this review, we summarize a role for microglia and monocytes/macrophages in acute ischemic stroke in the context of normal and metabolically compromised conditions.

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Section: Microgliasupporting

confidence: 64%

Microglia and Monocyte-Derived Macrophages in Stroke

2016

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“…We, therefore, used GCV treatment of CD11b-HSVtk transgenic cultures for effective ablation of microglial contribution. Microglia from transgenic CD11b-HSVtk mice become paralyzed or die in the presence of GCV (Heppner et al, 2005). LPS has been shown to contain impurities capable of signaling through other TLRs.…”

Section: Discussionmentioning

confidence: 99%

Microglia are required for astroglial toll‐like receptor 4 response and for optimal TLR2 and TLR3 response

Holm

Dræby

Owens

2012

Glia

114

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Within the central nervous system, astrocytes and microglia are the primary responders to endogenous ligands released upon injury and stress, as well as to infectious pathogens. Toll-like receptors (TLRs) are implicated in recognition of both types of stimulus. Whether astrocytes respond as strongly as microglia to TLR agonists remains contentious. In this study, we have rigorously purified astrocytes to determine their capacity for autonomous TLR response, in absence of microglia. We used flow cytometry and differential adhesion as well as a myeloid lineage-specific suicide gene to purify astrocytes from mixed glial cultures and measured their response to TLR agonists. Our results show that the response of astrocytes to TLR2 and TLR3 agonists is greatly enhanced by, and response to TLR4 agonists is completely dependent on, the presence of functional microglia. In the case of the TLR4 response to lipopolysaccharide, microglia exert their effect on astrocytes at least partially through release of soluble mediators that directly activate or facilitate astrocyte responses. Our findings underline the contribution of glial crosstalk in CNS responses to injury or inflammation. V

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“…Using transgenic mice carrying the selective ablation of proliferating microglia and undergoing experimental MS, it has been recently shown that the inhibition of microglia cells prevents the development and maintenance of the inflammatory CNS lesions [94]. Finally, a direct association between the intensity of microglia activation and EAE symptom gravity has been reported [2].…”

Section: The Eae Animal Modelmentioning

confidence: 99%

Estrogen anti-inflammatory activity in brain: A therapeutic opportunity for menopause and neurodegenerative diseases

Vegeto

Benedusi

Maggi

2008

Frontiers in Neuroendocrinology

273

206

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a b s t r a c tRecent studies highlight the prominent role played by estrogens in protecting the central nervous system (CNS) against the noxious consequences of a chronic inflammatory reaction. The neurodegenerative process of several CNS diseases, including Multiple Sclerosis, Alzheimer's and Parkinson's Diseases, is associated with the activation of microglia cells, which drive the resident inflammatory response. Chronically stimulated during neurodegeneration, microglia cells are thought to provide detrimental effects on surrounding neurons. The inhibitory activity of estrogens on neuroinflammation and specifically on microglia might thus be considered as a beneficial therapeutic opportunity for delaying the onset or progression of neurodegenerative diseases; in addition, understanding the peculiar activity of this female hormone on inflammatory signalling pathways will possibly lead to the development of selected anti-inflammatory molecules. This review summarises the evidence for the involvement of microglia in neuroinflammation and the anti-inflammatory activity played by estrogens specifically in microglia.

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Experimental autoimmune encephalomyelitis repressed by microglial paralysis

Cited by 677 publications

References 46 publications

Microglia and Monocyte-Derived Macrophages in Stroke

Microglia and Monocyte-Derived Macrophages in Stroke

Microglia are required for astroglial toll‐like receptor 4 response and for optimal TLR2 and TLR3 response

Estrogen anti-inflammatory activity in brain: A therapeutic opportunity for menopause and neurodegenerative diseases

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