Abstract:
BACKGROUND:The migration of peripheral immune cells and splenocytes to the ischemic brain is one of the major causes of delayed neuroinflammation after permanent large vessel stroke. Other groups have demonstrated that leukemia inhibitory factor (LIF), a cytokine that promotes neural cell survival through upregulation of antioxidant enzymes, promotes an anti-inflammatory phenotype in several types of immune cells. The goal of this study was to determine whether LIF treatment modulates the peripheral immune response after stroke. METHODS:Young male (3 month) Sprague-Dawley rats underwent sham surgery or permanent middle cerebral artery occlusion (MCAO). Animals were administered LIF (125 μg/kg) or PBS at 6, 24, and 48 h prior to euthanization at 72 h. Bone marrow-derived macrophages were treated with LIF (20 ng/ml) or PBS after stimulation with interferon gamma + LPS. Western blot was used to measure protein levels of CD11b, IL-12, interferon inducible protein-10, CD3, and the LIF receptor in spleen and brain tissue. ELISA was used to measure IL-10, IL-12, and interferon gamma. Isolectin was used to label activated immune cells in brain tissue sections. Statistical analysis was performed using one-way ANOVA and Student's t test. A Kruskal-Wallis test followed by Bonferroni-corrected Mann-Whitney tests was performed if data did not pass the D'Agostino-Pearson normality test. RESULTS:LIF-treated rats showed significantly lower levels of the LIF receptor and interferon gamma in the spleen and CD11b levels in the brain compared to their PBS-treated counterparts. Fluorescence from isolectin-binding immune cells was more prominent in the ipsilateral cortex and striatum after PBS treatment compared to LIF treatment. MCAO + LIF significantly decreased splenic levels of CD11b and CD3 compared to sham surgery. MCAO + PBS treatment significantly elevated splenic levels of interferon inducible protein-10 at 72 h after MCAO, while LIF treatment after MCAO returned interferon inducible protein 10 to sham levels. LIF administration with interferon gamma + LPS significantly reduced the IL-12/IL-10 production ratio compared to macrophages treated with interferon gamma + LPS alone. CONCLUSIONS:These data demonstrate that LIF promotes anti-inflammatory signaling through alterations of the IL-12/interferon gamma/interferon inducible protein 10 pathway.
journal_name
J Neuroinflammationjournal_title
Journal of neuroinflammationauthors
Davis SM,Collier LA,Winford ED,Leonardo CC,Ajmo CT Jr,Foran EA,Kopper TJ,Gensel JC,Pennypacker KRdoi
10.1186/s12974-018-1326-ysubject
Has Abstractpub_date
2018-10-15 00:00:00pages
288issue
1issn
1742-2094pii
10.1186/s12974-018-1326-yjournal_volume
15pub_type
杂志文章abstract:BACKGROUND:The neutrophil to lymphocyte ratio (NLR) has been shown to predict short- and long-term outcomes in ischemic stroke patients. We sought to explore the temporal profile of the plasma NLR in stroke patients treated with intravenous thrombolysis (IVT) and its relationship with intracranial bleeding complication...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-016-0680-x
更新日期:2016-08-26 00:00:00
abstract:BACKGROUND:Glutamate excitotoxicity contributes to oligodendrocyte and tissue damage in multiple sclerosis (MS). Intriguingly, glutamate level in plasma and cerebrospinal fluid of MS patients is elevated, a feature which may be related to the pathophysiology of this disease. In addition to glutamate transporters, level...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-8-63
更新日期:2011-06-03 00:00:00
abstract:BACKGROUND:Transforming growth factor β (TGF-β) is a cytokine having multiple functions in the central nervous system such as promoting repair mechanisms in degenerative diseases and stroke. To date, however, its neuroprotective effects in non-disease conditions have not been studied METHODS:With the aim of exploring ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-9-42
更新日期:2012-02-28 00:00:00
abstract:OBJECTIVES:The neurobiological basis for autism remains poorly understood. However, research suggests that environmentalfactors and neuroinflammation, as well as genetic factors, are contributors. This study aims to test the role that might be played by heat shock protein (HSP)70, transforming growth factor (TGF)-β2, C...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-9-265
更新日期:2012-12-11 00:00:00
abstract:BACKGROUND:Components of the innate immune complement system have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS); however, a comprehensive examination of complement expression in this disease has not been performed. This study therefore aimed to determine the expression of complement compone...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-10-119
更新日期:2013-09-26 00:00:00
abstract::Mesial temporal lobe epilepsy (mTLE) is a chronic and often treatment-refractory brain disorder characterized by recurrent seizures originating from the hippocampus. The pathogenic mechanisms underlying mTLE remain largely unknown. Recent clinical and experimental evidence supports a role of various inflammatory media...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-9-207
更新日期:2012-08-30 00:00:00
abstract::The complement cascade is a critical effector mechanism of the innate immune system that contributes to the rapid clearance of pathogens and dead or dying cells, as well as contributing to the extent and limit of the inflammatory immune response. In addition, some of the early components of this cascade have been clea...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章,评审
doi:10.1186/s12974-020-02024-8
更新日期:2020-11-25 00:00:00
abstract:BACKGROUND:Pain is one critical hallmark of inflammatory responses. A large number of studies have demonstrated that stromal cell-derived factor 1 (SDF1, also named as CXCL12) and its cognate receptor C-X-C chemokine receptor type 4 (CXCR4) play an important role in immune reaction and inflammatory processes. However, ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-015-0441-2
更新日期:2015-11-24 00:00:00
abstract:BACKGROUND:Complement activation via the lectin activation pathway (LP) has been identified as the key mechanism behind post-ischemic tissue inflammation causing ischemia-reperfusion injury (IRI) which can significantly impact the clinical outcome of ischemic disease. This work defines the contributions of each of the ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-016-0684-6
更新日期:2016-08-30 00:00:00
abstract:BACKGROUND:Immune activation, specifically activation of macrophages and resident microglia, leading to inflammation is a key component in the progression of spinal cord injury (SCI). Macrophages/microglia exist in two states-the classically activated M1 phenotype that confers pro-inflammatory effects or the alternativ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-018-1183-8
更新日期:2018-05-22 00:00:00
abstract:BACKGROUND:T helper (Th) 17 cells are a highly plastic subset of T cells, which in the context of neuroinflammation, are able to acquire pathogenic features originally attributed to Th1 cells (resulting in so called ex-Th17 cells). Thus, a strict separation between the two T cell subsets in the context of experimental ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-020-02021-x
更新日期:2020-11-26 00:00:00
abstract:OBJECTIVES:Autism is a developmental disorder characterized by social and emotional deficits, language impairments and stereotyped behaviors that manifest in early postnatal life. This study aims to clarify the relationship amongst absolute and relative concentrations of K+, Na+, Ca2+, Mg2+ and/or proinflammatory and p...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-8-142
更新日期:2011-10-15 00:00:00
abstract:BACKGROUND:Exposure to benzo(a)pyrene (BaP) was associated with cognitive impairments and some Alzheimer's disease (AD)-like pathological changes. However, it is largely unknown whether BaP exposure participates in the disease progression of AD. OBJECTIVES:To investigate the effect of BaP exposure on AD progression an...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-020-01925-y
更新日期:2020-08-31 00:00:00
abstract:BACKGROUND:Leukocytes are believed to be involved in delayed cell death following traumatic brain injury (TBI). However, data demonstrating that blood-borne inflammatory cells are present in the injured brain prior to the onset of secondary brain damage have been inconclusive. We therefore investigated both the interac...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-10-32
更新日期:2013-02-28 00:00:00
abstract:BACKGROUND:Opioid receptors are known to control neurotransmission of various peptidergic neurons, but their potential role in regulation of microglia and neuronal cell communications is unknown. We investigated the role of mu-opioid receptors (MOR) and delta-opioid receptors (DOR) on microglia in the regulation of apo...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-017-0844-3
更新日期:2017-04-14 00:00:00
abstract:BACKGROUND:The peroxisome proliferator-activated receptor (PPAR)-α activator, 5,8,11,14-eicosatetraynoic acid (ETYA), is an arachidonic acid analog. It is reported to inhibit up-regulation of pro-inflammatory genes; however, its underlying mechanism of action is largely unknown. In the present study, we focused on the ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-9-34
更新日期:2012-02-18 00:00:00
abstract:BACKGROUND:Liver X receptors (LXRs), including LXRα and LXRβ, are key regulators of transcriptional programs for both cholesterol homeostasis and inflammation in the brain. Here, the modes of action of LXRs and the epigenetic mechanisms regulating LXRβ expression in anterior cingulate cortex (ACC) of chronic inflammato...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-019-1507-3
更新日期:2019-06-29 00:00:00
abstract:BACKGROUND:Streptococcus pneumoniae meningitis is a serious inflammatory disease of the central nervous system (CNS) and is associated with high morbidity and mortality rates. The inflammatory processes initiated by recognition of bacterial components contribute to apoptosis in the hippocampal dentate gyrus. Brain-deri...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-017-0930-6
更新日期:2017-08-04 00:00:00
abstract:BACKGROUND:Obesity and its associated disorders are becoming a major health issue in many countries. The resulting low-grade inflammation not only affects the periphery but also the central nervous system. We set out to study, in a time-dependent manner, the effects of a high-fat diet on different regions of the centra...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-016-0666-8
更新日期:2016-08-26 00:00:00
abstract:BACKGROUND:Traumatic brain injury (TBI) initiates a neuroinflammatory cascade that contributes to substantial neuronal damage and behavioral impairment, and Toll-like receptor 4 (TLR4) is an important mediator of thiscascade. In the current study, we tested the hypothesis that curcumin, a phytochemical compound with po...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-11-59
更新日期:2014-03-27 00:00:00
abstract:BACKGROUND:Alzheimer's disease (AD) is a multifactorial disorder associated with the accumulation of soluble forms of beta-amyloid (Aβ) and its subsequent deposition into plaques. One of the major contributors to neuronal death is chronic and uncontrolled inflammatory activation of microglial cells around the plaques a...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-014-0229-9
更新日期:2015-01-16 00:00:00
abstract:BACKGROUND:Upregulated levels of 18-kDa translocator proteins (TSPO) and type 2 endocannabinoid receptors (CB2) are considered to reflect different aspects of microglia-related neuroinflammatory responses in the brain. Relative to the increase in the TSPO expression that occurs slightly later during neuroinflammation i...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-017-0851-4
更新日期:2017-03-29 00:00:00
abstract:BACKGROUND:After spinal cord injury (SCI), glial scarring is mainly formed around the lesion and inhibits axon regeneration. Recently, we reported that anti-β1 integrin antibody (β1Ab) had a therapeutic effect on astrocytes by preventing the induction of glial scar formation. However, the cellular components within the...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-020-02059-x
更新日期:2021-01-06 00:00:00
abstract:BACKGROUND:Repetitive mild traumatic brain injuries (rmTBI) are associated with cognitive deficits, inflammation, and stress-related events. We tested the effect of nutrient intake on the impact of rmTBI in an animal model of chronic traumatic encephalopathy (CTE) to study the pathophysiological mechanisms underlying t...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-018-1312-4
更新日期:2018-09-24 00:00:00
abstract:BACKGROUND:Neuroinflammation in utero may contribute to brain injury resulting in life-long neurological disabilities. The pivotal role of the efferent cholinergic anti-inflammatory pathway (CAP) in controlling inflammation, e.g., by inhibiting the HMGB1 release, via the macrophages' α7 nicotinic acetylcholine receptor...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-016-0567-x
更新日期:2016-05-10 00:00:00
abstract:BACKGROUND:Age-related macular degeneration (AMD) is a devastating eye disease causing irreversible vision loss in the elderly. Retinal pigment epithelium (RPE), the primary cell type that is afflicted in AMD, undergoes programmed cell death in the late stages of the disease. However, the exact mechanisms for RPE degen...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-018-1062-3
更新日期:2018-01-12 00:00:00
abstract:BACKGROUND:Neurogenic inflammation is orchestrated by a large number of neuropeptides. Tachykinins (substance P, neurokinin A and neurokinin B) are pro-inflammatory neuropeptides that may play an important role in some autoimmune neuroinflammatory diseases. Autoimmunity may have a role in the pathogenesis of autism in ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-8-180
更新日期:2011-12-21 00:00:00
abstract:BACKGROUND:The effectiveness of ginseng in preventing and treating various central nervous system (CNS) diseases has been widely confirmed. However, ginsenosides, the principal components of ginseng, are characterized by poor accessibility to the brain, and this pharmacokinetic-pharmacological paradox remains poorly ex...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-8-100
更新日期:2011-08-16 00:00:00
abstract::Microglia are the primary immunocompetent cells in brain tissue and microglia-mediated inflammation is associated with the pathogenesis of various neuronal disorders. Recently, many studies have shown that mesenchymal stem cells (MSCs) display a remarkable ability to modulate inflammatory and immune responses through ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-11-135
更新日期:2014-08-04 00:00:00
abstract:BACKGROUND:Parkinson's disease (PD) is characterized by selective degeneration of dopaminergic (DA) neurons of the substantia nigra pars compacta (SN) while neighboring ventral tegmental area (VTA) DA neurons are relatively spared. Mechanisms underlying the selective protection of the VTA and susceptibility of the SN a...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-018-1181-x
更新日期:2018-05-11 00:00:00