Targeting tumour necrosis factor-α in hypoxia and synaptic signalling

O’Connor, John

doi:10.1007/s11845-013-0911-4

Cited by 37 publications

(23 citation statements)

References 63 publications

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“…Recently, blockade of TNF α was shown to reduce apoptosis in the hippocampus after SAH [52]. This corresponds well to the extensive literature demonstrating a role for TNF α in neuronal apoptosis in other forms of neurological injury [53]. However, the antiapoptotic effects of TNF α blockade were not uniform throughout the brain, and a pre-rather than posttreatment paradigm was utilized in this study [52].…”

Section: Evidence For Inflammation In Animal Models Of Sahsupporting

confidence: 56%

Inflammation, Vasospasm, and Brain Injury after Subarachnoid Hemorrhage

Miller

Turan

Chau

et al. 2014

BioMed Research International

170

120

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Subarachnoid hemorrhage (SAH) can lead to devastating neurological outcomes, and there are few pharmacologic treatments available for treating this condition. Both animal and human studies provide evidence of inflammation being a driving force behind the pathology of SAH, leading to both direct brain injury and vasospasm, which in turn leads to ischemic brain injury. Several inflammatory mediators that are elevated after SAH have been studied in detail. While there is promising data indicating that blocking these factors might benefit patients after SAH, there has been little success in clinical trials. One of the key factors that complicates clinical trials of SAH is the variability of the initial injury and subsequent inflammatory response. It is likely that both genetic and environmental factors contribute to the variability of patients' post-SAH inflammatory response and that this confounds trials of anti-inflammatory therapies. Additionally, systemic inflammation from other conditions that affect patients with SAH could contribute to brain injury and vasospasm after SAH. Continuing work on biomarkers of inflammation after SAH may lead to development of patient-specific anti-inflammatory therapies to improve outcome after SAH.

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Section: Evidence For Inflammation In Animal Models Of Sahsupporting

confidence: 56%

Inflammation, Vasospasm, and Brain Injury after Subarachnoid Hemorrhage

Miller

Turan

Chau

et al. 2014

BioMed Research International

170

120

View full text Add to dashboard Cite

show abstract

“…Available evidence indicates that centrally acting Ang II promotes development of hypertension and other cardiovascular diseases 4, 9, 10 through induction of pro-inflammatory cytokines (PICs) in the PVN 11–13 . Of particular importance for the present study is that PICs have two well established modes of action 14–18 . Activation of PIC receptors and their downstream signaling cascades can acutely and chronically enhance neuronal activity by modulation of ion channel gating and by transcriptional regulation of gene expression, respectively 14–18 .…”

Section: Introductionmentioning

confidence: 99%

Ang II–Salt Hypertension Depends on Neuronal Activity in the Hypothalamic Paraventricular Nucleus but Not on Local Actions of Tumor Necrosis Factor-α

et al. 2014

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Development of angiotensin II (Ang II)-dependent hypertension involves microglial activation and proinflammatory cytokine actions in the hypothalamic paraventricular nucleus (PVN). Cytokines activate receptor signaling pathways that can both acutely grade neuronal discharge and trigger long-term adaptive changes that modulate neuronal excitability through gene transcription. Here, we investigated contributions of PVN cytokines to maintenance of hypertension induced by infusion of Ang II (150 ng/kg/min, SC) for 14 days in rats consuming a 2% NaCl diet. Results indicate that bilateral PVN inhibition with the GABA-A receptor agonist muscimol (100 pmol/50 nL) caused significantly greater reductions of renal and splanchnic sympathetic nerve activity (SNA) and mean arterial pressure (MAP) in hypertensive than normotensive rats (P<0.01). Thus ongoing PVN neuronal activity appears required for support of hypertension. Next, the role of the prototypical cytokine tumor necrosis factor alpha (TNF-α) was investigated. Whereas PVN injection of TNF-α (0.3 pmol/50 nL) acutely increased lumbar and splanchnic SNA and MAP, interfering with endogenous TNF-α by injection of etanercept (10 µg/50 nL) was without effect in hypertensive and normotensive rats. We next determined that although microglial activation in PVN was increased in hypertensive rats, bilateral injections of minocycline (0.5 µg/50 nL), an inhibitor of microglial activation, failed to reduce lumbar or splanchnic SNA or MAP in hypertensive or normotensive rats. Collectively, these findings indicate that established Ang II-salt hypertension is supported by PVN neuronal activity, but short term maintenance of SNA and ABP does not depend on ongoing local actions of TNF-α.

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“…A body of proinflammatory cytokines are rapidly elevated in the acute period including IL-6, TNF- α , and so on [36]; besides, the increased cytokines levels in the brain are dramatically higher than the corresponding levels in serum [37]. Generally, the existence of proinflammatory cytokines are required for preserving synaptic strength at excitatory synapses, and it is essential to synaptic plasticity [38, 39], but excessive secretion of proinflammatory cytokines may produce detrimental effects on the synapses [40]. …”

Section: The Interactions Between Functional Mechanisms and Synapsesmentioning

confidence: 99%

Therapeutic Potentials of Synapses after Traumatic Brain Injury: A Comprehensive Review

Wen

Li²,

Shen

et al. 2017

Neural Plasticity

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Massive studies have focused on the understanding of the pathobiology of cellular and molecular changes and injury mechanisms after traumatic brain injury (TBI), but very few studies have specially discussed the role of synapses in the context of TBI. This paper specifically highlights the role and therapeutic potentials of synapses after TBI. First, we review and conclude how synapses interact with constant structural, metabolic, neuroendocrine, and inflammatory mechanisms after TBI. Second, we briefly describe several key synaptic proteins involved in neuroplasticity, which may be novel neuronal targets for specific intervention. Third, we address therapeutic interventions in association with synapses after TBI. Finally, we concisely discuss the study gaps in the synapses after TBI, in hopes that this would provide more insights for future studies. Synapses play an important role in TBI; while the understandings on the synaptic participation in the treatments and prognosis of TBI are lacking, more studies in this area are warranted.

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Targeting tumour necrosis factor-α in hypoxia and synaptic signalling

Cited by 37 publications

References 63 publications

Inflammation, Vasospasm, and Brain Injury after Subarachnoid Hemorrhage

Inflammation, Vasospasm, and Brain Injury after Subarachnoid Hemorrhage

Ang II–Salt Hypertension Depends on Neuronal Activity in the Hypothalamic Paraventricular Nucleus but Not on Local Actions of Tumor Necrosis Factor-α

Therapeutic Potentials of Synapses after Traumatic Brain Injury: A Comprehensive Review

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