An Update on Inflammation in the Acute Phase of Intracerebral Hemorrhage

Chen, Sheng; Yang, Qingwu; Chen, Gang; Zhang, Junyi

doi:10.1007/s12975-014-0384-4

Cited by 217 publications

(158 citation statements)

References 48 publications

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“…Microglial activation has been demonstrated to be an important contributor to inflammation-related brain injury after ICH. 48,49 Dimethyl fumarate treated animals showed fewer activated microglia cells in the peri-hematomal region compared to vehicle treated animals. Consistent with our results discussed above, which demonstrate the anti-inflammatory effects of Dimethyl fumarate, Dimethyl fumarate-treated animals showed fewer activated microglial cells in the perihematoma, compared to vehicle-treated animals…”

Section: Discussionmentioning

confidence: 93%

“…5,6 Vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1), adhesion molecules expressed in the endothelium that are important in inflammation after injury, are increased upon activation of the nuclear factor-κB (NF-κB)-mediated tumor necrosis factor α (TNFα) signaling pathway. TNFα increases early-onset endothelial adhesion by protein kinase C-dependent upregulation of ICAM-1 expression, which can worsen outcomes following ICH.…”

Section: Introductionmentioning

confidence: 99%

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Dimethyl fumarate confers neuroprotection by casein kinase 2 phosphorylation of Nrf2 in murine intracerebral hemorrhage

Iniaghe

Krafft

Klebe

et al. 2015

Neurobiology of Disease

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Background and purpose Edema formation, inflammation and increased blood-brain barrier permeability contribute to poor outcomes after intracerebral hemorrhage (ICH). This study examined the therapeutic effect of Dimethyl fumarate (DMF), a fumaric acid ester that activates nuclear factor erythroid-2 related factor 2 (Nrf2) and Nrf2 heterodimerization effector musculo-aponeurotic fibrosacoma-G (MAFG) in a murine ICH model. Methods Male CD-1 mice (n=176) were subjected to intrastriatal infusion of bacterial collagenase (n=120), autologous blood (n=18) or sham surgery (n=30). After ICH, animals either received vehicle, Dimethyl fumarate (10mg or 100mg/kg) or casein kinase 2 inhibitor (E)-3-(2,3,4,5-tetrabromophenyl)acrylic acid (TBCA). Thirty-eight mice also received scrambled siRNA or MAFG siRNA 24 hours before ICH. Brain water content and neurological function were evaluated. Results Dimethyl fumarate reduced Evans blue extravasation, decreased brain water content, and improved neurological deficits at 24 and 72 hours after ICH. Casein kinase 2 inhibitor TBCA and MAFG siRNA prevented the effect of Dimethyl fumarate on brain edema and neurological function. After ICH, ICAM-1 levels increased and Casein kinase 2 levels decreased. Dimethyl fumarate reduced ICAM-1 but enhanced Casein kinase 2 levels. Again, Casein kinase 2 inhibitor TBCA and MAFG siRNA abolished the effect of Dimethyl fumarate on ICAM-1 and Casein kinase 2. Dimethyl fumarate preserved pNrf2 and MAFG expression in the nuclear lysate after ICH and the effect of Dimethyl fumarate was abolished by Casein kinase 2 inhibitor TBCA and MAFG siRNA. Dimethyl fumarate reduced microglia activation in peri-hematoma areas after ICH. The protective effect of Dimethyl fumarate on brain edema and neurological function was repeated in a blood injection mouse model. Conclusion Dimethyl fumarate ameliorated inflammation, reduced blood barrier permeability, and improved neurological outcomes by Casein kinase 2 and Nrf2 signaling pathways after experimental ICH in mice.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Dimethyl fumarate confers neuroprotection by casein kinase 2 phosphorylation of Nrf2 in murine intracerebral hemorrhage

Iniaghe

Krafft

Klebe

et al. 2015

Neurobiology of Disease

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“…Most previous studies have focused on the role of inflammatory factors. As a result, endogenous anti-inflammatory factors that can ameliorate ICH-induced inflammation have been overlooked (6)(7)(8). Thus, targeting endogenous anti-inflammatory factors could provide insights into the development of new ICH therapies.…”

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confidence: 99%

A20 Ameliorates Intracerebral Hemorrhage–Induced Inflammatory Injury by Regulating TRAF6 Polyubiquitination

Meng

Zhao

Zhou

et al. 2017

The Journal of Immunology

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Reducing excessive inflammation is beneficial for the recovery from intracerebral hemorrhage (ICH). Here, the roles and mechanisms of A20 (TNFAIP3), an important endogenous anti-inflammatory factor, are examined in ICH. A20 expression in the PBMCs of ICH patients and an ICH mouse model was detected, and the correlation between A20 expression and neurologic deficits was analyzed. A20 expression was increased in PBMCs and was negatively related to the modified Rankin Scale score. A20 expression was also increased in mouse perihematomal tissues. A20−/− and A20-overexpressing mice were generated to further analyze A20 function. Compared with wild-type (WT) mice, A20−/− and A20-overexpressing mice showed significant increases and decreases, respectively, in hematoma volume, neurologic deficit score, mortality, neuronal degeneration, and proinflammatory factors. Moreover, WT-A20−/− parabiosis was established to explore the role of A20 in peripheral blood in ICH injury. ICH-induced damage, including brain edema, neurologic deficit score, proinflammatory factors, and neuronal apoptosis, was reduced in A20−/− parabionts compared with A20−/− mice. Finally, the interactions between TRAF6 and Ubc13 and UbcH5c were increased in A20−/− mice compared with WT mice; the opposite occurred in A20-overexpressing mice. Enhanced IκBα degradation and NF-κB activation were observed in A20−/− mice, but the results were reversed in A20-overexpressing mice. These results suggested that A20 is involved in regulating ICH-induced inflammatory injury in both the central and peripheral system and that A20 reduces ICH-induced inflammation by regulating TRAF6 polyubiquitination. Targeting A20 may thus be a promising therapeutic strategy for ICH.

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“…(87, 124, 133, 147–149) Brain-intrinsic microglia are the first inflammatory cell type to react to brain injury. By releasing inflammatory mediators, they contribute to BBB breakdown and leukocyte influx from blood.…”

Section: Stroke and The Sphingolipid Pathwaymentioning

confidence: 99%

Critical Role of the Sphingolipid Pathway in Stroke: a Review of Current Utility and Potential Therapeutic Targets

Sun

Keep

Hua

et al. 2016

Transl. Stroke Res.

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Sphingolipids are a series of cell membrane derived lipids which act as signaling molecules and play a critical role in cell death and survival, proliferation, recognition and migration. Sphingosine 1 phosphate acts as a key signaling molecule and regulates lymphocyte trafficking, glial cell activation, vasoconstriction, endothelial barrier function and neuronal death pathways which plays a critical role in numerous neurological conditions. Stroke is a second leading cause of death all over the world and effective therapies are still in great demand, including ischemic stroke and hemorrhagic stroke as well as the post stroke repair. Significantly, sphingolipid activities change after stroke and correlate with stroke outcome, which has promoted efforts to testify whether sphingolipid pathway could be a novel therapeutic target in stroke. Sphingolipid metabolic pathway, the connection between the pathway and stroke, as well as therapeutic interventions to manipulate the pathway to reduce stroke-induced brain injury are discussed in this review.

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An Update on Inflammation in the Acute Phase of Intracerebral Hemorrhage

Cited by 217 publications

References 48 publications

Dimethyl fumarate confers neuroprotection by casein kinase 2 phosphorylation of Nrf2 in murine intracerebral hemorrhage

Dimethyl fumarate confers neuroprotection by casein kinase 2 phosphorylation of Nrf2 in murine intracerebral hemorrhage

A20 Ameliorates Intracerebral Hemorrhage–Induced Inflammatory Injury by Regulating TRAF6 Polyubiquitination

Critical Role of the Sphingolipid Pathway in Stroke: a Review of Current Utility and Potential Therapeutic Targets

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