Tumor Necrosis Factor Receptor-1 is Essential for LPS-Induced Sensitization and Tolerance to Oxygen—Glucose Deprivation in Murine Neonatal Organotypic Hippocampal Slices

Markus, Tina; Cronberg, Tobias; Cilio, Corrado; Pronk, Cornelis Jan; Wieloch, Tadeusz; Ley, David

doi:10.1038/jcbfm.2008.90

Cited by 22 publications

(26 citation statements)

References 41 publications

(47 reference statements)

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“…After OGD, however, the TNF-α/IFN-γ treatment was toxic for the neurons. This finding corroborates animal models in which the combination of HI with inflammation (LPS treatment) increases the severity of the injury (36) and with in vitro studies showing increased TNF-α toxicity after OGD (37). …”

Section: Discussionsupporting

confidence: 84%

Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) Signaling and Cell Death in the Immature Central Nervous System after Hypoxia-Ischemia and Inflammation

Kichev

Rousset

Baburamani

et al. 2014

Journal of Biological Chemistry

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Background: TRAIL induces apoptosis through interaction with receptor DR5.Results: Animal model of neonatal hypoxia-ischemia (HI) and primary cultures subjected to oxygen glucose deprivation show increased expression of TRAIL and DR5; TRAIL is toxic for primary neurons.Conclusion: TRAIL-mediated cell death contributes to brain injury after HI.Significance: TRAIL signaling pathways may represent a valid drug target for protection against neonatal HI.

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Section: Discussionsupporting

confidence: 84%

Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) Signaling and Cell Death in the Immature Central Nervous System after Hypoxia-Ischemia and Inflammation

Kichev

Rousset

Baburamani

et al. 2014

Journal of Biological Chemistry

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“…26 Moreover, both TNFa and LTa, signal through TNF receptor 1, 27 which appears critical for endotoxin-mediated sensitization to oxygen glucose deprivation in vitro. 28 In the current study we, therefore, explored the effects of the TNF gene cluster cytokines TNFa, LTa and LTb on endotoxin-mediated sensitization to HI insult in the neonatal mouse, and associated cellular activation and molecular changes using complete deletion of the TNF cluster, pretreatment with endotoxin and the Rice-Vannucci model of unilateral occlusion of left common carotid artery and 30-min hypoxia in 8% oxygen. 29 Our results show that the TNF cluster cytokines are upregulated by endotoxin in vivo, that their deletion prevents the normally observed microglial and vascular activation following application of endotoxin alone, and that the TNF cluster null mice also no longer exhibit the endotoxin-mediated sensitizing effect on HI insult.…”

mentioning

confidence: 99%

TNF gene cluster deletion abolishes lipopolysaccharide-mediated sensitization of the neonatal brain to hypoxic ischemic insult

Kendall

Hirstova

Horn

et al. 2011

Laboratory Investigation

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In the current study, we explored the role of TNF cluster cytokines on the lipopolysaccharide (LPS)-mediated, synergistic increase in brain injury after hypoxic ischemic insult in postnatal day 7 mice. Pretreatment with moderate doses of LPS (0.3 mg/g) resulted in particularly pronounced synergistic injury within 12 h. Systemic application of LPS alone resulted in a strong upregulation of inflammation-associated cytokines TNFa, LTb, interleukin (IL) 1b, IL6, chemokines, such as CXCL1, and adhesion molecules E-Selectin, P-Selectin and intercellular adhesion molecule-1 (ICAM1), as well as a trend toward increased LTa levels in day 7 mouse forebrain. In addition, it was also associated with strong activation of brain blood vessel endothelia and local microglial cells. Here, deletion of the entire TNF gene cluster, removing TNFa, LTb and LTa completely abolished endotoxin-mediated increase in the volume of cerebral infarct. Interestingly, the same deletion also prevented endothelial and microglial activation following application of LPS alone, suggesting the involvement of these cell types in bringing about the LPS-mediated sensitization to neonatal brain injury. KEYWORDS: encephalopathy; hypoxia; inflammation; ischemia; neonate; TNF Although bacteria and viruses can directly infect and injure developing brain, infections occurring outside the brain frequently will also have a damaging effect. Congenital infections appear to contribute up to 5% of cerebral palsy cases 1,2 and may sensitize the brain to perinatal hypoxic ischemic (HI) insult. [3][4][5] This synergistic effect was also reproduced in mammalian and avian animal models, combining HI insult and the lipopolysaccharide break-down product of bacteria in HI animal models.6-10 However, the molecular mediators of this endotoxin effect in vivo are currently still unknown.Both in vitro and in vivo studies show that endotoxin will upregulate numerous cytokines and chemokines, 11 upregulate signaling enzymes, such as inducible nitrogen oxide synthase (iNOS), and cyclo-oxygenase-2 (COX2) and enhance the expression of adhesion molecules on parenchymal microglia and the brain vascular endothelium. 12-15Follow on molecular studies reveal that these effects are transmitted through the classical endotoxin receptors, primarily the toll-like receptor 4 (TLR4), on blood vessel endothelia and microglia, 16,17 and involve MyD88 and NF-kappa-B components of the innate immunity cascade. 17In particular, endotoxin-induced pro-inflammatory cytokines, including TNFa and interleukin 1b (IL1b) are known to have a number of deleterious effects, including a direct toxic effect on neurones and vulnerable oligodendrocyte precursors, 18,19 astrogliosis with release of nitric oxide, and mitochondrial dysfunction, 20 as well as microglial activation with release of nitric oxide, superoxide and a panel of other inflammation-associated molecules.

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“…TNF receptor 1 is critical for LPS-mediated sensitization to oxygen glucose deprivation in vitro. 91 Moreover, deletion of the TNF gene cluster abolishes LPS-mediated sensitization of the neonatal brain to a hypoxic-ischaemic insult. 68 TNFa treatment is toxic to oligodendrocyte precursors 92 and potentiates IFNc-induced toxicity to these cells in vitro.…”

Section: Death Receptorsmentioning

confidence: 99%

Inflammation‐induced sensitization of the brain in term infants

Fleiss

Tann

Degos

et al. 2015

Develop Med Child Neuro

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COXPerinatal insults are a leading cause of infant mortality and amongst survivors are frequently associated with neurocognitive impairment, cerebral palsy (CP), and seizure disorders. The events leading to perinatal brain injury are multifactorial. This review describes how one subinjurious factor affecting the brain sensitizes it to a second injurious factor, causing an exacerbated injurious cascade. We will review the clinical and experimental evidence, including observations of high rates of maternal and fetal infections in term-born infants with neonatal encephalopathy and cerebral palsy. In addition, we will discuss preclinical evidence for the sensitizing effects of inflammation on injuries, such as hypoxia-ischaemia, our current understanding of the mechanisms underpinning the sensitization process, and the possibility for neuroprotection. PERINATAL BRAIN INJURY IN THE TERM-BORN INFANTIntrapartum neonatal deaths are the third leading cause of global childhood mortality. 1 In addition, each year perinatal insults are estimated to be responsible for more than one million new cases of neonatal encephalopathy, and nearly half a million infants with impairments such as cerebral palsy (CP).2 Infants exposed to a perinatal insult typically present with encephalopathy, a descriptive term for a clinical constellation of neurological dysfunctions in the term-born that includes difficulty with initiating and maintaining respiration; depression of tone and reflexes; subnormal levels of consciousness; and seizures.3 Whilst often assumed to result solely from acute intrapartum hypoxic-ischaemia, the precise contribution of hypoxia is likely to vary according to the definition of encephalopathy used, the range of competing risks, and the care setting. 3,4 Presumed hypoxia-ischaemia is diagnosed based on reduced Apgar scores and acidosis, 5 and the combination of progressive hypoxia, hypercarbia, and acidosis is often referred to as asphyxia. 6 Encephalopathy resulting from hypoxia-ischaemia can be clearly diagnosed only in a small number of cases in which a sentinel event, such as placental abruption, uterine rupture, cord prolapse, or shoulder dystocia, is clearly present. Clinical studies have identified a number of other important antepartum and intrapartum risk factors for neonatal encephalopathy. [7][8][9][10] In low-income settings, where access to skilled birth attendants and emergency obstetric intervention is often limited, the probability of intrapartum hypoxic events contributing to neonatal encephalopathy is increased.2,9,11 However, in general, neonatal encephalopathy is likely to be a multifactorial condition with complex aetiology, encompassing several causal events, with strong evidence that fetal exposure to infection contributes. 12 CONCEPT OF INFLAMMATION-INDUCED SENSITIZATIONAn increasingly common model for the complex and multifactorial process of perinatal brain injury involves sensitization, 13-15 whereby factors not severe enough by themselves to induce significant brain damage make the developi...

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Tumor Necrosis Factor Receptor-1 is Essential for LPS-Induced Sensitization and Tolerance to Oxygen—Glucose Deprivation in Murine Neonatal Organotypic Hippocampal Slices

Cited by 22 publications

References 41 publications

Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) Signaling and Cell Death in the Immature Central Nervous System after Hypoxia-Ischemia and Inflammation

Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) Signaling and Cell Death in the Immature Central Nervous System after Hypoxia-Ischemia and Inflammation

TNF gene cluster deletion abolishes lipopolysaccharide-mediated sensitization of the neonatal brain to hypoxic ischemic insult

Inflammation‐induced sensitization of the brain in term infants

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