Tumor necrosis factor-α attenuates N-methyl-d-aspartate-mediated neurotoxicity in neonatal rat hippocampus

Liu, Xiao Hong; Xu, Haiyan; Barks, John

doi:10.1016/s0006-8993(99)02126-5

Cited by 27 publications

(19 citation statements)

References 54 publications

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“…Co-injections of TNF-! and NMDA into the hippocampus reduced excitotoxic injury; however, intrastriatal co-injections did not alter the severity of injury (Liu et al 1999). TNF-!…”

Section: Neuroprotective Effects Of Tnf-amentioning

confidence: 89%

Divergent Roles for Tumor Necrosis Factor-α in the Brain

Sriram

O’Callaghan

2007

Jrnl Neuroimmune Pharm

199

140

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Proinflammatory cytokines and chemokines have been implicated in the pathogenesis of several neurological and neurodegenerative disorders. Prominent among such factors is the pleiotropic cytokine, tumor necrosis factor (TNF)-alpha. Under normal physiological conditions, TNF-alpha orchestrates a diverse array of functions involved in immune surveillance and defense, cellular homeostasis, and protection against certain neurological insults. However, paradoxical effects of this cytokine have been observed. TNF-alpha is elicited in the brain following injury (ischemia, trauma), infection (HIV, meningitis), neurodegeneration (Alzheimer's, Parkinson's), and chemically induced neurotoxicity. The multifarious identity for this cytokine appears to be influenced by several mechanisms. Among the most prominent are the regulation of TNFalpha-induced NF-kappaB activation by adapter proteins such as TRADD and TRAF, and second, the heterogeneity of microglia and their distribution pattern across brain regions. Here, we review the differential role of TNF-alpha in response to brain injury, with emphasis on neurodegeneration, and discuss the possible mechanisms for such diverse and region-specific effects.

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“…Co-injections of TNF-! and NMDA into the hippocampus reduced excitotoxic injury; however, intrastriatal co-injections did not alter the severity of injury (Liu et al 1999). TNF-!…”

Section: Neuroprotective Effects Of Tnf-amentioning

confidence: 89%

Divergent Roles for Tumor Necrosis Factor-α in the Brain

Sriram

O’Callaghan

2007

Jrnl Neuroimmune Pharm

199

140

View full text Add to dashboard Cite

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“…Interestingly, inhibition of TNF-a by antibodies prevents ischemic injury (Barone et al, 1997), while mice deficient in TNFR1 are resistant to sepsis-induced encephalopathy (Alexander et al, 2008) and excitotoxic damage is prevented in brain slices from TNFR1 knockout mice (Bernardino et al, 2005). However, TNF-a was shown to attenuate NMDA-mediated neurotoxicity (Liu et al, 1999b) and TNFR1 knock-out mice are reported to be more vulnerable to brain ischemia (Bruce et al, 1996). Differential effects were also observed since inhibition of TNF-a was found to simultaneous attenuate or exacerbate injury depending on the brain region (Galasso et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Astrocyte reactivity to unconjugated bilirubin requires TNF‐α and IL‐1β receptor signaling pathways

Fernandes

Barateiro

Falcão

et al. 2010

Glia

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Jaundice and sepsis are common neonatal conditions that can lead to neurodevelopment sequelae, namely if present at the same time. We have reported that tumor necrosis factor (TNF)-α and interleukin (IL)-1β are produced by cultured neurons and mainly by glial cells exposed to unconjugated bilirubin (UCB). The effects of these cytokines are mediated by cell surface receptors through a nuclear factor (NF)-κB-dependent pathway that we have showed to be activated by UCB. The present study was designed to evaluate the role of TNF-α and IL-1β signaling on astrocyte reactivity to UCB in rat cortical astrocytes. Exposure of astrocytes to UCB increased the expression of both TNF-α receptor (TNFR)1 and IL-1β receptor (IL-1R)1, but not TNFR2, as well as their activation, observed by augmented binding of receptors' molecular adaptors, TRAF2 and TRAF6, respectively. Silencing of TNFR1, using siRNA technology, or blockade of IL-1β cascade, using its endogenous antagonist, IL-1 receptor antagonist (IL-1ra), prevented UCB-induced cytokine release and NF-κB activation. Interestingly, lack of TNF-α signal transduction reduced UCB-induced cell death for short periods of incubation, although an increase was observed after extended exposure; in contrast, inhibition of IL-1β cascade produced a sustained blockade of astrocyte injury by UCB. Together, our data show that inflammatory pathways are activated during in vitro exposure of rat cortical astrocytes to UCB and that this activation is prolonged in time. This supports the concept that inflammatory pathways play a role in brain damage by UCB, and that they may represent important pharmacological targets.

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“…When cells are exposed to excess glutamate, a cell will die from either rapid necrosis via an influx of Na + and Cl -or delayed apoptosis via a Ca 2+ -dependent pathway. Glutamate excitotoxicity can arise due to a variety of circumstances, including blunt force trauma, lack of proper cell oxygenation, hypoglycemia, and inappropriate release of glutamate from degenerating neurons [8][9][10].…”

mentioning

confidence: 99%

Glutamate in CNS Neurodegeneration and Cognition and its Regulation by GCPII Inhibition

Rahn

Slusher²,

Kaplin³

2012

CMC

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Glutamate, first identified in 1866, is the primary excitatory neurotransmitter in the brain. While it is critically important in many highly regulated cortical functions such as learning and memory, glutamate can be much like the magic the Sorcerer's Apprentice used in Goethe's poem: when conjured under unregulated conditions glutamate can get quickly out of control and lead to deleterious consequences. Two broad types of glutamate receptors, the ionotropic and metabotropic, facilitate glutamatergic neurotransmission in the CNS and play key roles in regulating cognitive function. Excessive activation of these receptors leads to excitotoxicity, especially in brain regions that are developmentally and regionally vulnerable to this kind of injury. Dysregulation of glutamate signaling leads to neurodegeneration that plays a role in a number of neuropsychiatric diseases, prompting the development and utilization of novel strategies to balance the beneficial and deleterious potential of this important neurotransmitter. Inhibition of the enzyme glutamate carboxypeptidase II (GCPII) is one method of manipulating glutamate neurotransmission. Positive outcomes (decreased neuronal loss, improved cognition) have been demonstrated in preclinical models of ALS, stroke, and Multiple Sclerosis due to inhibition of GCPII, suggesting this method of glutamate regulation could serve as a therapeutic means for treating neurodegeneration and cognitive impairment.

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Tumor necrosis factor-α attenuates N-methyl-d-aspartate-mediated neurotoxicity in neonatal rat hippocampus

Cited by 27 publications

References 54 publications

Divergent Roles for Tumor Necrosis Factor-α in the Brain

Divergent Roles for Tumor Necrosis Factor-α in the Brain

Astrocyte reactivity to unconjugated bilirubin requires TNF‐α and IL‐1β receptor signaling pathways

Glutamate in CNS Neurodegeneration and Cognition and its Regulation by GCPII Inhibition

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