Scavenger receptor SRA attenuates microglia activation and protects neuroinflammatory injury in intracerebral hemorrhage

Yang, Zhao; Zhong, Shanchuan; Liu, Yongping; Shen, Haikang; Yuan, Bangqing

doi:10.1016/j.jneuroim.2014.11.010

Cited by 17 publications

(17 citation statements)

References 34 publications

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“…The presence of hepcidin in neurons is subject to debate. Some studies have shown that neurons are able to produce hepcidin in response to microglia activation (Yang, Zhong, Liu, Shen, & Yuan, ), whereas others have reported that only astrocytes and microglia can secrete hepcidin (Urrutia et al, ). Our results indicate that neurons do not synthesize hepcidin but probably do enhance hepcidin production indirectly by releasing pro‐inflammatory cytokines, which in turn activate microglia and astrocytes (graphical abstract).…”

Section: Discussionmentioning

confidence: 99%

Predominant role of microglia in brain iron retention in Sanfilippo syndrome, a pediatric neurodegenerative disease

Puy

Darwiche

Trudel

et al. 2018

Glia

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Neuroinflammation and iron accumulation are hallmarks of a variety of adult neurodegenerative diseases. In Sanfilippo syndrome (mucopolysaccharidosis type III, MPSIII, a pediatric neurodegenerative disease that shares some features with adult neurodegenerative diseases), the progressive accumulation of heparan sulfate oligosaccharides (HSOs) induces microglia and astrocytes to produce pro-inflammatory cytokines leading to severe neuroinflammation. The objectives of the present study were (1) to measure the local iron concentration and to assess iron metabolism in the brain of a MPSIIIB murine model and (2) to identify the brain cells involved in this accumulation. We found that iron accumulation in MPSIIIB mice primarily affected the cerebral cortex where hepcidin levels were higher than in wild-type mice, and increased with aging. This increase was correlated with low expression of ferroportin 1 (FPN1), and thus brain iron retention. Moreover, we showed in vitro that HSOs are directly responsible for the production of hepcidin and the relative decrease in FPN1 expression when added to cultures of microglia and, to a lesser extent, to cultures of astrocytes. In contrast, no significant differences were observed in neurons. Hepcidin induction results from activation of the TLR4 pathway and STAT3 signaling, and leads to iron retention within microglia. Our results show that microglia have a key role in cerebral hepcidin overexpression and thus in the brain iron accumulation observed in the MPSIIIB model.

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Section: Discussionmentioning

confidence: 99%

Predominant role of microglia in brain iron retention in Sanfilippo syndrome, a pediatric neurodegenerative disease

Puy

Darwiche

Trudel

et al. 2018

Glia

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“…SRA was highly expressed in erythrocyte lysate-treated microglia. Genetic SRA ablation increased microglia activation and cytokine production, and sensitized mice to ICH-induced neuron injury [21]. SRA down-regulated inflammatory response expression in microglia by suppressing TLR4-induced activation [22].…”

Section: Sramentioning

confidence: 99%

Haematoma scavenging in intracerebral haemorrhage: from mechanisms to the clinic

Wang

Sun

et al. 2017

J Cellular Molecular Medi

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The products of erythrocyte lyses, haemoglobin (Hb) and haem, are recognized as neurotoxins and the main contributors to delayed cerebral oedema and tissue damage after intracerebral haemorrhage (ICH). Finding a means to efficiently promote absorption of the haemolytic products (Hb and haem) around the bleeding area in the brain through stimulating the function of the body's own garbage cleaning system is a novel clinical challenge and critical for functional recovery after ICH. In this review, available information of the brain injury mechanisms underlying ICH and endogenous haematoma scavenging system is provided. Meanwhile, potential intervention strategies are discussed. Intracerebral blood itself has ‘toxic’ effects beyond its volume effect after ICH. Haptoglobin–Hb–CD163 as well as haemopexin–haem–LRP1 is believed to be the most important endogenous scavenging pathway which participates in blood components resolution following ICH. PPARγ–Nrf2 activates the aforementioned clearance pathway and then accelerates haematoma clearance. Meanwhile, the scavenger receptors as novel targets for therapeutic interventions to treat ICH are also highlighted.

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“…Emerging studies demonstrated the role of SR‐A in microglia‐mediated inflammatory response (Yang et al . ). Yang et al .…”

Section: Discussionmentioning

confidence: 97%

“…Yang et al . ()reported that SR‐A inhibition increases microglia activation and cytokine production, and sensitizes mice to intracerebral hemorrhage‐induced neuron injury. On the contrary, other studies showed that SR‐A is a positive regulator of neuroinflammation (Godoy et al .…”

Section: Discussionmentioning

confidence: 99%

“…Emerging studies demonstrated the role of SR-A in microglia-mediated inflammatory response (Yang et al 2015). Yang et al (2015)reported that SR-A inhibition increases microglia activation and cytokine production, and sensitizes mice to intracerebral hemorrhage-induced neuron injury. On the contrary, other studies showed that SR-A is a positive regulator of neuroinflammation (Godoy et al 2012;Xu et al 2012).…”

Section: Discussionmentioning

confidence: 99%

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Vascular endothelial growth factor is neuroprotective against ischemic brain injury by inhibiting scavenger receptor A expression on microglia

Han

Chen

et al. 2017

Journal of Neurochemistry

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Vascular endothelial growth factor (VEGF) is a secreted mitogen associated with angiogenesis. VEGF has long been thought to be a potent neurotrophic factor for the survival of spinal cord neurons. However, the role of VEGF in the regulation of ischemic brain injury remains unclear. In this study, rats were subjected to MCAO (middle cerebral artery occlusion) followed by intraperitoneal injection of VEGF165 (10 mg/kg) immediately after surgery and once daily until the day 10. The expression of target genes was assayed using qPCR, western blot and immunofluorescence to investigate the role of VEGF165 in regulating ischemic brain injury. We found that VEGF165 significantly inhibited MCAO-induced up-regulation of Scavenger receptor class A (SR-A) on microglia in a VEGFR1-dependent manner. VEGF165 inhibited lipopolysaccharide (LPS)-induced expression of proinflammatory cytokines IL-1β, tumor necrosis factor alpha (TNF-α) and iNOS in microglia. More importantly, the role of VEGF165 in inhibiting neuroinflammation is partially abolished by SR-A over-expression. SR-A further reduced the protective effect of VEGF165 in ischemic brain injury. These data suggest that VEGF165 suppresses neuroinflammation and ischemic brain injury by inhibiting SR-A expression, thus offering a new target for prevention of ischemic brain injury.

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Scavenger receptor SRA attenuates microglia activation and protects neuroinflammatory injury in intracerebral hemorrhage

Cited by 17 publications

References 34 publications

Predominant role of microglia in brain iron retention in Sanfilippo syndrome, a pediatric neurodegenerative disease

Predominant role of microglia in brain iron retention in Sanfilippo syndrome, a pediatric neurodegenerative disease

Haematoma scavenging in intracerebral haemorrhage: from mechanisms to the clinic

Vascular endothelial growth factor is neuroprotective against ischemic brain injury by inhibiting scavenger receptor A expression on microglia

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