scholarly journals Toll-Like Receptor 9: A New Target of Ischemic Preconditioning in the Brain

2008 ◽  
Vol 28 (5) ◽  
pp. 1040-1047 ◽  
Author(s):  
Susan L Stevens ◽  
Thomas MP Ciesielski ◽  
Brenda J Marsh ◽  
Tao Yang ◽  
Delfina S Homen ◽  
...  
Keyword(s):  
Brain Injury ◽  
Ischemic Injury ◽  
Ischemic Brain Injury ◽  
Dependent Manner ◽  
Cpg Odn ◽  
Toll Like Receptor ◽  
Ischemic Brain ◽  
Cpg Oligodeoxynucleotide ◽  
Tlr9 Ligand

Preconditioning with lipopolysaccharide (LPS), a toll-like receptor 4 (TLR4) ligand, provides neuroprotection against subsequent cerebral ischemic brain injury, through a tumor necrosis factor (TNF)α-dependent process. Here, we report the first evidence that another TLR, TLR9, can induce neuroprotection. We show that the TLR9 ligand CpG oligodeoxynucleotide (ODN) can serve as a potent preconditioning stimulus and provide protection against ischemic brain injury. Our studies show that systemic administration of CpG ODN 1826 in advance of brain ischemia (middle cerebral artery occlusion (MCAO)) reduces ischemic damage up to 60% in a dose- and time-dependent manner. We also offer evidence that CpG ODN preconditioning can provide direct protection to cells of the central nervous system, as we have found marked neuroprotection in modeled ischemia in vitro. Finally, we show that CpG preconditioning significantly increases serum TNFα levels before MCAO and that TNFα is required for subsequent reduction in damage, as mice lacking TNFα are not protected against ischemic injury by CpG preconditioning. Our studies show that preconditioning with a TLR9 ligand induces neuroprotection against ischemic injury through a mechanism that shares common elements with LPS preconditioning via TLR4.

scholarly journals Lipopolysaccharide Sensitizes Neonatal Hypoxic-Ischemic Brain Injury in a MyD88-Dependent Manner

2009 ◽  
Vol 183 (11) ◽  
pp. 7471-7477 ◽  
Author(s):  
Xiaoyang Wang ◽  
Linnea Stridh ◽  
Wenli Li ◽  
Justin Dean ◽  
Anders Elmgren ◽  
...  
Keyword(s):  
Brain Injury ◽  
Ischemic Brain Injury ◽  
Dependent Manner ◽  
Ischemic Brain ◽  
Hypoxic Ischemic Brain Injury

Ischemic brain injury in vitro: protective effects of NMDA receptor antagonists and calmidazolium

1990 ◽  
Vol 528 (1) ◽  
pp. 133-137 ◽  
Author(s):  
Roman Pohorecki ◽  
Gerald L. Becker ◽  
Pamela J. Reilly ◽  
Dennis F. Landers
Keyword(s):  
Brain Injury ◽  
Nmda Receptor ◽  
Ischemic Brain Injury ◽  
Nmda Receptor Antagonists ◽  
Protective Effects ◽  
Receptor Antagonists ◽  
Ischemic Brain

scholarly journals Intranasal Administration of Human MSC for Ischemic Brain Injury in the Mouse: In Vitro and In Vivo Neuroregenerative Functions

PLoS ONE ◽  
2014 ◽  
Vol 9 (11) ◽  
pp. e112339 ◽  
Author(s):  
Vanessa Donega ◽  
Cora H. Nijboer ◽  
Luca Braccioli ◽  
Ineke Slaper-Cortenbach ◽  
Annemieke Kavelaars ◽  
...  
Keyword(s):  
Brain Injury ◽  
Intranasal Administration ◽  
Ischemic Brain Injury ◽  
Ischemic Brain

scholarly journals The Acute-Phase Protein PTX3 is an Essential Mediator of Glial Scar Formation and Resolution of Brain Edema after Ischemic Injury

2013 ◽  
Vol 34 (3) ◽  
pp. 480-488 ◽  
Author(s):  
Beatriz Rodriguez-Grande ◽  
Matimba Swana ◽  
Loan Nguyen ◽  
Pavlos Englezou ◽  
Samaneh Maysami ◽  
...  
Keyword(s):  
Brain Injury ◽  
Brain Edema ◽  
Acute Phase ◽  
Acute Phase Protein ◽  
Ischemic Injury ◽  
Glial Scar ◽  
Scar Formation ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Phase Protein

Acute-phase proteins (APPs) are key effectors of the immune response and are routinely used as biomarkers in cerebrovascular diseases, but their role during brain inflammation remains largely unknown. Elevated circulating levels of the acute-phase protein pentraxin-3 (PTX3) are associated with worse outcome in stroke patients. Here we show that PTX3 is expressed in neurons and glia in response to cerebral ischemia, and that the proinflammatory cytokine interleukin-1 (IL-1) is a key driver of PTX3 expression in the brain after experimental stroke. Gene deletion of PTX3 had no significant effects on acute ischemic brain injury. In contrast, the absence of PTX3 strongly compromised blood–brain barrier integrity and resolution of brain edema during recovery after ischemic injury. Compromised resolution of brain edema in PTX3-deficient mice was associated with impaired glial scar formation and alterations in scar-associated extracellular matrix production. Our results suggest that PTX3 expression induced by proinflammatory signals after ischemic brain injury is a critical effector of edema resolution and glial scar formation. This highlights the potential role for inflammatory molecules in brain recovery after injury and identifies APPs, in particular PTX3, as important targets in ischemic stroke and possibly other brain inflammatory disorders.

scholarly journals HDAC9 Silencing Exerts Neuroprotection Against Ischemic Brain Injury via miR-20a-Dependent Downregulation of NeuroD1

2021 ◽  
Vol 14 ◽  
Author(s):  
Liangjun Zhong ◽  
Jinxiang Yan ◽  
Haitao Li ◽  
Lei Meng
Keyword(s):  
Ischemic Stroke ◽  
Brain Injury ◽  
Neuronal Apoptosis ◽  
Inflammatory Factors ◽  
Cerebral Stroke ◽  
Inflammatory Factor ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Factor Release

Cerebral stroke is an acute cerebrovascular disease that is a leading cause of death and disability worldwide. Stroke includes ischemic stroke and hemorrhagic strokes, of which the incidence of ischemic stroke accounts for 60–70% of the total number of strokes. Existing preclinical evidence suggests that inhibitors of histone deacetylases (HDACs) are a promising therapeutic intervention for stroke. In this study, the purpose was to investigate the possible effect of HDAC9 on ischemic brain injury, with the underlying mechanism related to microRNA-20a (miR-20a)/neurogenic differentiation 1 (NeuroD1) explored. The expression of HDAC9 was first detected in the constructed middle cerebral artery occlusion (MCAO)-provoked mouse model and oxygen-glucose deprivation (OGD)-induced cell model. Next, primary neuronal apoptosis, expression of apoptosis-related factors (Bax, cleaved caspase3 and bcl-2), LDH leakage rate, as well as the release of inflammatory factors (TNF-α, IL-1β, and IL-6) were evaluated by assays of TUNEL, Western blot, and ELISA. The relationships among HDAC9, miR-20a, and NeuroD1 were validated by in silico analysis and ChIP assay. HDAC9 was highly-expressed in MCAO mice and OGD-stimulated cells. Silencing of HDAC9 inhibited neuronal apoptosis and inflammatory factor release in vitro. HDAC9 downregulated miR-20a by enriching in its promoter region, while silencing of HDCA9 promoted miR-20a expression. miR-20a targeted Neurod1 and down-regulated its expression. Silencing of HDAC9 diminished OGD-induced neuronal apoptosis and inflammatory factor release in vitro as well as ischemic brain injury in vivo by regulating the miR-20a/NeuroD1 signaling. Overall, our study revealed that HDAC9 silencing could retard ischemic brain injury through the miR-20a/Neurod1 signaling.

scholarly journals Neuroprotective effect of astrocyte-derived IL-33 in neonatal hypoxic-ischemic brain injury

2019 ◽  
Author(s):  
Mengya Jiao ◽  
Xiangyong Li ◽  
Xiaodi Wang ◽  
Liying Chen ◽  
Baohong Yuan ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Brain Injury ◽  
Neurotrophic Factor ◽  
Inflammatory Responses ◽  
Neuroprotective Effect ◽  
Brain Infarction ◽  
Neurological Deficits ◽  
Dependent Manner ◽  
Ischemic Brain

Abstract Background: Interleukin-33 (IL-33) is a well-recognized pleiotropic cytokine which plays crucial roles in immune regulation and inflammatory responses. Recent studies suggest that IL-33 and its receptor ST2 are involved in the pathogenesis of neurological diseases. Here, we explore the effect of IL-33/ST2 signaling in neonatal hypoxic-ischemic (HI) brain injury and elucidate the underlying mechanisms of action. Methods: The brain HI model was established in neonatal C57BL/6 mice by left common carotid artery occlusion with 90 min hypoxia, and treated with IL-33 at a dose of 0.2 μg/day i.p. for three days. TTC staining and neurobehavioral observation were used to evaluate the HI brain injury. Immunofluorescence and flow cytometry were applied to determine the expression of IL-33 and its receptor ST2 on brain CNS cells, cell proliferation and apoptosis. OGD experiment was used to assay the viability of astrocytes and neurons. RT-qPCR was used to measure the expression of neurotrophic factor-associated genes. Results: The expression level of IL-33 was markedly enhanced in astrocytes 24 h after cerebral HI in neonatal mice. Exogenous delivery of IL-33 significantly alleviated brain injury 7 d after HI, whereas ST2 deficiency exacerbated brain infarction and neurological deficits post HI. Flow cytometry analyses demonstrated high levels of ST2 expression on astrocytes, and the expression of ST2 was further elevated after HI. Intriguingly, IL-33 treatment apparently improved astrocyte response and attenuated HI-induced astrocyte apoptosis through ST2 signaling pathways. Further in vitro studies revealed that IL-33-activated astrocytes released a series of neurotrophic factors, which are critical for raising neuronal survival against oxygen glucose deprivation. Conclusions: The activation of IL-33/ST2 signaling in the ischemic brain improves astrocyte response, which in turn affords protection to ischemic neurons in a glial-derived neurotrophic factor-dependent manner.

Enalapril and moexipril protect from free radical-induced neuronal damage in vitro and reduce ischemic brain injury in mice and rats

1999 ◽  
Vol 373 (1) ◽  
pp. 21-33 ◽  
Author(s):  
Alexander Ravati ◽  
Vera Junker ◽  
Maria Kouklei ◽  
Barbara Ahlemeyer ◽  
Carsten Culmsee ◽  
...  
Keyword(s):  
Free Radical ◽  
Brain Injury ◽  
Neuronal Damage ◽  
Ischemic Brain Injury ◽  
Ischemic Brain
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