CCL11 enhances excitotoxic neuronal death by producing reactive oxygen species in microglia

Parajuli, Bijay; Horiuchi, Hiroshi; Mizuno, Tetsuya; Takeuchi, Hideyuki; Suzumura, Akio

doi:10.1002/glia.22892

Cited by 122 publications

(98 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Specifically, there was significant elevation of IL-1α, IL-1β, IL-3, IP-10, IL-5, TGFβ, IL-12 (p40), IL-12 (p70), IL-17, IL-13, RANTES, IFNγ, GM-CSF, TNFα, MIP-1α, MCP-3, EOTAXIN, and MCP-1 levels within the infarct of the stroked mice compared to the equivalent area of the cortex in sham mice. Of these, IL-1, IP-10, IL-17, IL-13, IFNγ, TNFα, EOTAXIN, and MCP-1 (CCL2) have all been linked to cytotoxicity in neurons (Gelbard et al, 1993; Sui et al, 2006; Takeuchi et al, 2006; Thornton et al, 2006; Mizuno et al, 2008; Tzartos et al, 2008; Park et al, 2009; Shichita et al, 2009; Yang et al, 2011; Kang et al, 2012; Parajuli et al, 2015) (Table 1). …”

Section: Resultsmentioning

confidence: 99%

Glial scars are permeable to the neurotoxic environment of chronic stroke infarcts

Zbesko

Nguyen

Yang

et al. 2018

Neurobiology of Disease

102

View full text Add to dashboard Cite

Following stroke, the damaged tissue undergoes liquefactive necrosis, a stage of infarct resolution that lasts for months although the exact length of time is currently unknown. One method of repair involves reactive astrocytes and microglia forming a glial scar to compartmentalize the area of liquefactive necrosis from the rest of the brain. The formation of the glial scar is a critical component of the healing response to stroke, as well as other central nervous system (CNS) injuries. The goal of this study was to evaluate the toxicity of the extracellular fluid present in areas of liquefactive necrosis and determine how effectively it is segregated from the remainder of the brain. To accomplish this goal, we used a mouse model of stroke in conjunction with an extracellular fluid toxicity assay, fluorescent and electron microscopy, immunostaining, tracer injections into the infarct, and multiplex immunoassays. We confirmed that the extracellular fluid present in areas of liquefactive necrosis following stroke is toxic to primary cortical and hippocampal neurons for at least 7 weeks following stroke, and discovered that although glial scars are robust physical and endocytic barriers, they are nevertheless permeable. We found that molecules present in the area of liquefactive necrosis can leak across the glial scar and are removed by a combination of paravascular clearance and microglial endocytosis in the adjacent tissue. Despite these mechanisms, there is delayed atrophy, cytotoxic edema, and neuron loss in regions adjacent to the infarct for weeks following stroke. These findings suggest that one mechanism of neurodegeneration following stroke is the failure of glial scars to impermeably segregate areas of liquefactive necrosis from surviving brain tissue.

show abstract

Section: Resultsmentioning

confidence: 99%

Glial scars are permeable to the neurotoxic environment of chronic stroke infarcts

Zbesko

Nguyen

Yang

et al. 2018

Neurobiology of Disease

102

View full text Add to dashboard Cite

show abstract

“…In primary cell lines obtained from mice, treatment with exogenous CCL11 increases microglial migration and induces the production of microglial reactive oxygen species, directly contributing to neuronal death in co-culture systems [18]. Previous studies have shown that serum CCL11 levels rise acutely in a mouse model of traumatic brain injury [8].…”

Section: Discussionmentioning

confidence: 99%

CCL11 (Eotaxin-1) Levels Predict Long-Term Functional Outcomes in Patients Following Ischemic Stroke

Roy-O’Reilly

Ritzel

Conway

et al. 2017

Transl. Stroke Res.

View full text Add to dashboard Cite

Circulating levels of the pro-inflammatory cytokine C-C motif chemokine 11 (CCL11, also known as eotaxin-1) are increased in several animal models of neuroinflammation, including traumatic brain injury and Alzheimer’s disease. Increased levels of CCL11 have also been linked to decreased neurogenesis in mice. We hypothesized that circulating CCL11 levels would increase following ischemic stroke in mice and humans and that higher CCL11 levels would correlate with poor-long term recovery in patients. As predicted, circulating levels of CCL11 in both young and aged mice increased significantly 24 hours after experimental stroke. However, CCL11 levels were decreased in ischemic stroke patients compared to controls at 24 hours after stroke. Interestingly, lower post-stroke CCL11 levels were independently predictive of increased stroke severity and poorer functional outcomes in patients twelve months after ischemic stroke. These results illustrate the differences in the murine and human inflammatory response to ischemic stroke. In addition, it suggests CCL11 as a candidate biomarker for the prediction of acute and long-term functional outcomes in ischemic stroke patients.

show abstract

“…Both AOPP and MDA may be also marked in erythrocytes [74, 75]. Furthermore, the following are also measured in the CSF: levels of MDA and IsoP [54, 76, 77], ceramides [78], chemokine 11 (CCL11) [79], AOPP, and a decreased level of total thiol groups [80]. …”

Section: The Importance Of Os In Msmentioning

confidence: 99%

New Insights into the Role of Oxidative Stress Mechanisms in the Pathophysiology and Treatment of Multiple Sclerosis

Adamczyk

Adamczyk-Sowa

2016

Oxidative Medicine and Cellular Longevity

114

100

View full text Add to dashboard Cite

Multiple sclerosis (MS) is a multifactorial disease of the central nervous system (CNS) characterized by an inflammatory process and demyelination. The etiology of the disease is still not fully understood. Therefore, finding new etiological factors is of such crucial importance. It is suspected that the development of MS may be affected by oxidative stress (OS). In the acute phase OS initiates inflammatory processes and in the chronic phase it sustains neurodegeneration. Redox processes in MS are associated with mitochondrial dysfunction, dysregulation of axonal bioenergetics, iron accumulation in the brain, impaired oxidant/antioxidant balance, and OS memory. The present paper is a review of the current literature about the role of OS in MS and it focuses on all major aspects. The article explains the mechanisms of OS, reports unique biomarkers with regard to their clinical significance, and presents a poorly understood relationship between OS and neurodegeneration. It also provides novel methods of treatment, including the use of antioxidants and the role of antioxidants in neuroprotection. Furthermore, adding new drugs in the treatment of relapse may be useful. The article considers the significance of OS in the current treatment of MS patients.

show abstract

CCL11 enhances excitotoxic neuronal death by producing reactive oxygen species in microglia

Cited by 122 publications

References 66 publications

Glial scars are permeable to the neurotoxic environment of chronic stroke infarcts

Glial scars are permeable to the neurotoxic environment of chronic stroke infarcts

CCL11 (Eotaxin-1) Levels Predict Long-Term Functional Outcomes in Patients Following Ischemic Stroke

New Insights into the Role of Oxidative Stress Mechanisms in the Pathophysiology and Treatment of Multiple Sclerosis

Contact Info

Product

Resources

About