A novel brain injury mechanism after intracerebral hemorrhage: The interaction between heme products and the immune system

Loftspring, Matthew C.; Hansen, Claus D.; Clark, Joseph F.

doi:10.1016/j.mehy.2009.08.002

Cited by 22 publications

(19 citation statements)

References 32 publications

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“…In aged rats, treatment with deferoxamine, an iron chelator, greatly reduced the number of activated microglia/macrophages and the overall ROS production in the striatum [94]. Unconjugated bilirubin and bilirubin oxidative species are hypothesized to activate microglia in vivo , resulting in production of proinflammatory cytokines [95]. However, in a mouse animal model, unconjugated bilirubin infusion with the whole blood to create the ICH, there was a reduction in microglia but increase in neutrophils at 24 hours [96].…”

Section: Intracerebral Hemorrhagementioning

confidence: 99%

Microglial Responses after Ischemic Stroke and Intracerebral Hemorrhage

Taylor

Sansing

2013

Clinical and Developmental Immunology

350

302

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Stroke is a leading cause of death worldwide. Ischemic stroke is caused by blockage of blood vessels in the brain leading to tissue death, while intracerebral hemorrhage (ICH) occurs when a blood vessel ruptures, exposing the brain to blood components. Both are associated with glial toxicity and neuroinflammation. Microglia, as the resident immune cells of the central nervous system (CNS), continually sample the environment for signs of injury and infection. Under homeostatic conditions, they have a ramified morphology and phagocytose debris. After stroke, microglia become activated, obtain an amoeboid morphology, and release inflammatory cytokines (the M1 phenotype). However, microglia can also be alternatively activated, performing crucial roles in limiting inflammation and phagocytosing tissue debris (the M2 phenotype). In rodent models, microglial activation occurs very early after stroke and ICH; however, their specific roles in injury and repair remain unclear. This review summarizes the literature on microglial responses after ischemic stroke and ICH, highlighting the mediators of microglial activation and potential therapeutic targets for each condition.

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Section: Intracerebral Hemorrhagementioning

confidence: 99%

Microglial Responses after Ischemic Stroke and Intracerebral Hemorrhage

Taylor

Sansing

2013

Clinical and Developmental Immunology

350

302

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“…Iron-mediated free radical damage, which is associated with cerebrovascular disease, is thought to be involved in neuronal cell injury in acute brain pathological states including ischemia and intracerebral hemorrhage and in the neuropathology of several degenerative diseases, such as Alzheimer's disease (AD) and Parkinson disease (PD) [1][2][3][4] . Iron, which is released from heme after hemoglobin breakdown, accumulates in the parenchyma.…”

Section: Introductionmentioning

confidence: 99%

Carvacrol protects neuroblastoma SH-SY5Y cells against Fe2+-induced apoptosis by suppressing activation of MAPK/JNK-NF-κB signaling pathway

et al. 2015

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Aim: Carvacrol (2-methyl-5-isopropylphenol), a phenolic monoterpene in the essential oils of the genera Origanum and Thymus, has been shown to exert a variety of therapeutic effects. Here we examined whether carvacrol protected neuroblastoma SH-SY5Y cells against Fe 2+ -induced apoptosis and explored the underlying mechanisms. Methods: Neuroblastoma SH-SY5Y cells were incubated with Fe 2+ for 24 h, and the cell viability was assessed with CCK-8 assay. TUNEL assay and flow cytometric analysis were performed to evaluate cell apoptosis. The mRNA levels of pro-inflammatory cytokines and NF-κB p65 were determined using qPCR. The expression of relevant proteins was determined using Western blot analysis or immunofluorescence staining. Results: Treatment of SH-SY5Y cells with Fe 2+ (50-200 μmol/L) dose-dependently decreased the cell viability, which was significantly attenuated by pretreatment with carvacrol (164 and 333 μmol/L). Treatment with Fe 2+ increased the Bax level and caspase-3 activity, and decreased the Bcl-2 level, resulting in cell apoptosis. Furthermore, treatment with Fe 2+ significantly increased the gene expression of IL-1β, IL-6 and TNF-α, and induced the nuclear translocation of NF-κB. Treatment with Fe 2+ also significantly increased the phosphorylation of p38, ERK, JNK and IKK in the cells. Pretreatment with carvacrol significantly inhibited Fe 2+ -induced activation of NF-κB, expression of the pro-inflammatory cytokines, and cell apoptosis. Moreover, pretreatment with carvacrol inhibited Fe 2+ -induced phosphorylation of JNK and IKK, but not p38 and ERK in the cells. Conclusion: Carvacrol protects neuroblastoma SH-SY5Y cells against Fe 2+ -induced apoptosis, which may result from suppressing the MAPK/JNK-NF-κB signaling pathways.

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“…Treatment was efficacious as early as the first day and by improving all outcomes significantly, supporting the contention that toxic blood metabolites are significant in early brain injury [66]. Both ferrous and ferric iron are prooxidant molecules and ROS may promote the transcription of NF- κ B and activator protein-1 [67], thus activating inflammatory pathways.…”

Section: Early Brain Injurymentioning

confidence: 87%

To Look Beyond Vasospasm in Aneurysmal Subarachnoid Haemorrhage

Cossu

Messerer

Oddo

et al. 2014

BioMed Research International

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Delayed cerebral vasospasm has classically been considered the most important and treatable cause of mortality and morbidity in patients with aneurysmal subarachnoid hemorrhage (aSAH). Secondary ischemia (or delayed ischemic neurological deficit, DIND) has been shown to be the leading determinant of poor clinical outcome in patients with aSAH surviving the early phase and cerebral vasospasm has been attributed to being primarily responsible. Recently, various clinical trials aimed at treating vasospasm have produced disappointing results. DIND seems to have a multifactorial etiology and vasospasm may simply represent one contributing factor and not the major determinant. Increasing evidence shows that a series of early secondary cerebral insults may occur following aneurysm rupture (the so-called early brain injury). This further aggravates the initial insult and actually determines the functional outcome. A better understanding of these mechanisms and their prevention in the very early phase is needed to improve the prognosis. The aim of this review is to summarize the existing literature on this topic and so to illustrate how the presence of cerebral vasospasm may not necessarily be a prerequisite for DIND development. The various factors determining DIND that worsen functional outcome and prognosis are then discussed.

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A novel brain injury mechanism after intracerebral hemorrhage: The interaction between heme products and the immune system

Cited by 22 publications

References 32 publications

Microglial Responses after Ischemic Stroke and Intracerebral Hemorrhage

Microglial Responses after Ischemic Stroke and Intracerebral Hemorrhage

Carvacrol protects neuroblastoma SH-SY5Y cells against Fe2+-induced apoptosis by suppressing activation of MAPK/JNK-NF-κB signaling pathway

To Look Beyond Vasospasm in Aneurysmal Subarachnoid Haemorrhage

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