Microglia as Mediators of Inflammatory and Degenerative Diseases

González‐Scarano, Francisco; Baltuch, Gordon H.

doi:10.1146/annurev.neuro.22.1.219

Cited by 928 publications

(710 citation statements)

References 119 publications

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“…Mounting evidence suggests that neutrophils in particular might be mediators of secondary brain damage after ICH. Microglia, which constitute as many as 12% of the cells in the central nervous system (Gonzalez-Scarano and Baltuch, 1999), are the first non-neuronal cells to respond to central nervous system injury. When fully activated by either neuronal cell death or other processes, they become phagocytic.…”

Section: Cellular Components Of Inflammationmentioning

confidence: 99%

Inflammation after Intracerebral Hemorrhage

Wang

Doré

2007

J Cereb Blood Flow Metab

572

609

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Intracerebral hemorrhage (ICH) is a devastating clinical event without effective therapies. Increasing evidence suggests that inflammatory mechanisms are involved in the progression of ICH-induced brain injury. Inflammation is mediated by cellular components, such as leukocytes and microglia, and molecular components, including prostaglandins, chemokines, cytokines, extracellular proteases, and reactive oxygen species. Better understanding of the role of the ICH-induced inflammatory response and its potential for modulation might have profound implications for patient treatment. In this review, a summary of the available literature on the inflammatory responses after ICH is presented along with discussion of some of the emerging opportunities for potential therapeutic strategies. In the near future, additional strategies that target inflammation could offer exciting new promise in the therapeutic approach to ICH.

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Section: Cellular Components Of Inflammationmentioning

confidence: 99%

Inflammation after Intracerebral Hemorrhage

Wang

Doré

2007

J Cereb Blood Flow Metab

572

609

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“…However, inflammation often damages surrounding tissues. Several studies show that brain inflammation aggravates ischemic and traumatic brain injury (Giulian and Vaca, 1993;Holmin et al, 1995), and is involved in progression of neurodegenerative disorders such as Alzheimer's and Parkinson's diseases (Gonzalez-Scarano and Baltuch, 1999;Vila et al, 2001). Therefore, control of the duration and extent of brain inflammation is an emerging therapeutic target to treat and/or prevent both acute and chronic brain diseases (Feuerstein et al, 1997;Hoozemans et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Adenosine induces hemeoxygenase‐1 expression in microglia through the activation of phosphatidylinositol 3‐kinase and nuclear factor E2‐related factor 2

Min

Kim

Jou

et al. 2008

Glia

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Adenosine, a purine nucleoside, has been reported to suppress the inflammatory responses of microglia in the brain. However, the underlying mechanisms of its anti-inflammatory action are unclear at present. Here we show that adenosine reduces the increase in intracellular reactive oxygen species (ROS) through expression of an antioxidant enzyme, hemeoxygenase-1 (HO-1). The H 2 O 2 -induced intracellular ROS level was significantly low in microglia pretreated with adenosine for 3-6 h, compared with that in untreated cells. Adenosine induced HO-1 mRNA and protein expression within 3 h, which was maintained for up to 12 h. Nuclear factor E2-related factor 2 (Nrf2), a transcription factor, and phosphatidylinositol 3-kinase (PI3K) and Akt pathways appear to mediate HO-1 expression. In response to adenosine, Nrf2 translocated from the cytosol to nuclei, and bound to the antioxidant response element (ARE). Adenosine enhanced HO-1 promoter activity in an ARE-dependent manner. Moreover, the nucleoside stimulated Akt phosphorylation, and suppressors of PI3K (LY294002 and wortmannin) reduced adenosine-induced HO-1 expression. However, we propose that the effects of adenosine are independent of adenosine receptors, since agonists and antagonists of A1, A2a, and A3 had little effect on the regulation of intracellular ROS and HO-1 expression. Our results collectively suggest that adenosine acts as an endogenous regulator of brain inflammation via modulation of microglial ROS production. V

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“…Several studies have demonstrated a deleterious role of microglia in the pathology of PD (197)(198)(199). Microglia are resident immunocompetent and phagocygotic cells in the CNS (197).…”

Section: Microgliamentioning

confidence: 99%

“…Microglia are resident immunocompetent and phagocygotic cells in the CNS (197). In response to a variety of pathological events, such as infection, inflammation, trauma, ischemia, and neurodegenerative diseases, they become activated and act as scavengers (198,200). The resting microglia then quickly migrate towards the lesion site, proliferate, become hypertrophic, change the expression of receptors and enzymes, and produce immune response molecules and toxic molecules, such as pro-inflammatory cytokines, prostaglandins and complement proteins, and ROS (197,(201)(202)(203).…”

Section: Microgliamentioning

confidence: 99%

“…Regardless of the origin, inflammation is clearly involved in the pathogenesis of PD. It must be emphasized, however, that both microgliosis and astrogliosis are unlikely to be specific for PD, as neuroinflammatory processes contribute to several neurodegenerative disorders, such as Alzheimer's disease (AD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and progressive supranuclear palsy (197,198,210).…”

Section: Microgliamentioning

confidence: 99%

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