TLR-3 receptor activation protects the very immature brain from ischemic injury

Shi, Hui; Gabarin, Nadia; Hickey, Edward; Askalan, Rand

doi:10.1186/1742-2094-10-104

Cited by 18 publications

(30 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, type I IFN signaling in brain microvascular endothelial cells was required for the cerebral ischemic protection, suggesting that the protection of poly-IC preconditioning against cerebral ischemia was achieved mainly by the type I IFN signaling to maintain the blood-brain barrier. Additionally, poly-IC preconditioning can activate the expression levels of TRIF and IRF3 in the ischemic brain tissue and increase the generation of IFN-β [ 68 , 71 ], which further supports the protective effect of the TRIF-IRF signaling pathway in cerebral ischemia (Figure 1 D). However, poly-IC preconditioning also significantly inhibited NF-κB activity and the generation of the pro-inflammatory cytokines TNF-α and IL-6 in the ischemic brain tissue and cultured cells [ 68 , 71 ].…”

Section: Introductionmentioning

confidence: 66%

Function and mechanism of toll-like receptors in cerebral ischemic tolerance: from preconditioning to treatment

Wang

Xiong

Chen

et al. 2015

J Neuroinflammation

View full text Add to dashboard Cite

Increasing evidence suggests that toll-like receptors (TLRs) play an important role in cerebral ischemia-reperfusion injury. The endogenous ligands released from ischemic neurons activate the TLR signaling pathway, resulting in the production of a large number of inflammatory cytokines, thereby causing secondary inflammation damage following cerebral ischemia. However, the preconditioning for minor cerebral ischemia or the preconditioning with TLR ligands can reduce cerebral ischemic injury by regulating the TLR signaling pathway following ischemia in brain tissue (mainly, the inhibition of the TLR4/NF-κB signaling pathway and the enhancement of the interferon regulatory factor-dependent signaling), resulting in TLR ischemic tolerance. Additionally, recent studies found that postconditioning with TLR ligands after cerebral ischemia can also reduce ischemic damage through the regulation of the TLR signaling pathway, showing a significant therapeutic effect against cerebral ischemia. These studies suggest that the ischemic tolerance mediated by TLRs can serve as an important target for the prevention and treatment of cerebral ischemia. On the basis of describing the function and mechanism of TLRs in mediating cerebral ischemic damage, this review focuses on the mechanisms of cerebral ischemic tolerance induced by the preconditioning and postconditioning of TLRs and discusses the clinical application of TLRs for ischemic tolerance.

show abstract

Section: Introductionmentioning

confidence: 66%

Function and mechanism of toll-like receptors in cerebral ischemic tolerance: from preconditioning to treatment

Wang

Xiong

Chen

et al. 2015

J Neuroinflammation

View full text Add to dashboard Cite

show abstract

“…Disruption of these processes at any level may derail subsequent developmental processes leading to network dysfunction. Second, the expression profile of immune receptors and pattern recognition receptors is different in the developing and adult brain 53 (reviewed in ref. 48 ), and therefore these cells may be poised for exaggerated responses to inflammatory stimuli.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory cytokine-induced changes in neural network activity measured by waveform analysis of high-content calcium imaging in murine cortical neurons

Clarkson

Kahoud

McCarthy

et al. 2017

Sci Rep

View full text Add to dashboard Cite

During acute neuroinflammation, increased levels of cytokines within the brain may contribute to synaptic reorganization that results in long-term changes in network hyperexcitability. Indeed, inflammatory cytokines are implicated in synaptic dysfunction in epilepsy and in an array of degenerative and autoimmune diseases of the central nervous system. Current tools for studying the impact of inflammatory factors on neural networks are either insufficiently fast and sensitive or require complicated and costly experimental rigs. Calcium imaging offers a reasonable surrogate for direct measurement of neuronal network activity, but traditional imaging paradigms are confounded by cellular heterogeneity and cannot readily distinguish between glial and neuronal calcium transients. While the establishment of pure neuron cultures is possible, the removal of glial cells ignores physiologically relevant cell-cell interactions that may be critical for circuit level disruptions induced by inflammatory factors. To overcome these issues, we provide techniques and algorithms for image processing and waveform feature extraction using automated analysis of spontaneous and evoked calcium transients in primary murine cortical neuron cultures transduced with an adeno-associated viral vector driving the GCaMP6f reporter behind a synapsin promoter. Using this system, we provide evidence of network perturbations induced by the inflammatory cytokines TNFα, IL1β, and IFNγ.

show abstract

“…; Shi et al . ). The differences may be due to the developmental differences in TLR induction (Shi et al .…”

Section: The Global Burden Of Hypoxic–ischaemic Brain Injurymentioning

confidence: 97%

“…The differences may be due to the developmental differences in TLR induction (Shi et al . ). Consistent with this, preterm neonates (<30 weeks) have attenuated innate immune responses to TLR agonists in the first 28 days of age (Marchant et al .…”

Section: The Global Burden Of Hypoxic–ischaemic Brain Injurymentioning

confidence: 97%

See 1 more Smart Citation

The fetus at the tipping point: modifying the outcome of fetal asphyxia

Dhillon

Lear

Galinsky

et al. 2018

The Journal of Physiology

View full text Add to dashboard Cite

Brain injury around birth is associated with nearly half of all cases of cerebral palsy. Although brain injury is multifactorial, particularly after preterm birth, acute hypoxia-ischaemia is a major contributor to injury. It is now well established that the severity of injury after hypoxia-ischaemia is determined by a dynamic balance between injurious and protective processes. In addition, mothers who are at risk of premature delivery have high rates of diabetes and antepartum infection/inflammation and are almost universally given treatments such as antenatal glucocorticoids and magnesium sulphate to reduce the risk of death and complications after preterm birth. We review evidence that these common factors affect responses to fetal asphyxia, often in unexpected ways. For example, glucocorticoid exposure dramatically increases delayed cell loss after acute hypoxia-ischaemia, largely through secondary hyperglycaemia. This critical new information is important to understand the effects of clinical treatments of women whose fetuses are at risk of perinatal asphyxia.

show abstract

TLR-3 receptor activation protects the very immature brain from ischemic injury

Cited by 18 publications

References 47 publications

Function and mechanism of toll-like receptors in cerebral ischemic tolerance: from preconditioning to treatment

Function and mechanism of toll-like receptors in cerebral ischemic tolerance: from preconditioning to treatment

Inflammatory cytokine-induced changes in neural network activity measured by waveform analysis of high-content calcium imaging in murine cortical neurons

The fetus at the tipping point: modifying the outcome of fetal asphyxia

Contact Info

Product

Resources

About