Abstract:
BACKGROUND:Fenofibrate, a PPAR-α activator, has shown promising results as a neuroprotective therapy, with proposed anti-inflammatory and anti-oxidant effects. However, it displays poor blood-brain barrier permeability leading to some ambiguity over its mechanism of action. Experimentally induced brain injury has been shown to elicit a hepatic acute phase response that modulates leukocyte recruitment to the injured brain. Here, we sought to discover whether one effect of fenofibrate might include the suppression of the acute phase response (APR) following brain injury. METHODS:A 1-h intraluminal thread middle cerebral artery occlusion (MCAO) model followed by a 6-h reperfusion was performed in C57/BL6 mice. Quantitative reverse transcriptase-polymerase chain reaction was then used to measure hepatic expression of chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine ligand 10 (CXCL10) and serum amyloid A-1 (SAA-1), and immunohistochemical analysis was used to quantify brain and hepatic neutrophil infiltration following stroke. RESULTS:The MCAO and sham surgery induced the expression of all three acute phase reactants. A 14-day fenofibrate pre-treatment decreased reactant production, infarct volume, and neutrophil recruitment to the brain and liver, which is a hallmark of the APR. CONCLUSIONS:The data highlight a novel mechanism of action for fenofibrate and lend further evidence towards the promotion of its use as a prophylactic therapy in patients at risk of cerebral ischaemia. Further research is required to elucidate the mechanistic explanation underlying its actions.
journal_name
J Neuroinflammationjournal_title
Journal of neuroinflammationauthors
Losey P,Ladds E,Laprais M,Guevel B,Burns L,Bordet R,Anthony DCdoi
10.1186/s12974-015-0295-7subject
Has Abstractpub_date
2015-05-22 00:00:00pages
99issn
1742-2094pii
10.1186/s12974-015-0295-7journal_volume
12pub_type
杂志文章abstract:BACKGROUND:Some children with autism spectrum disorders (ASD) are characterized by fluctuating behavioral symptoms following immune insults, persistent gastrointestinal (GI) symptoms, and a lack of response to the first-line intervention measures. These children have been categorized as the ASD-inflammatory subtype (AS...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-014-0187-2
更新日期:2014-10-27 00:00:00
abstract:BACKGROUND:Chemokine (C-X3-C motif) ligand 1 (CX3CL1)/ CX3C chemokine receptor 1 (CX3CR1) signaling is important in modulating the communication between neurons and resident microglia/migrated macrophages in the central nervous system (CNS). Although CX3CR1 deficiency is associated with an improved outcome following is...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-11-26
更新日期:2014-02-03 00:00:00
abstract::Chronic pain often occurs in the elderly, particularly in the patients with neurodegenerative disorders such as Alzheimer's disease (AD). Although studies indicate that chronic pain correlates with cognitive decline, it is unclear whether chronic pain accelerates AD pathogenesis. In this review, we provide evidence th...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章,评审
doi:10.1186/s12974-019-1608-z
更新日期:2019-11-06 00:00:00
abstract:BACKGROUND:Necrotizing enterocolitis (NEC) is an acute gut inflammatory disorder that occurs in preterm infants in the first weeks after birth. Infants surviving NEC often show impaired neurodevelopment. The mechanisms linking NEC lesions with later neurodevelopment are poorly understood but may include proinflammatory...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-018-1201-x
更新日期:2018-06-09 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: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:BACKGROUND:Endoplasmic reticulum (ER) stress is a hallmark of neurodegenerative diseases such as multiple sclerosis (MS). However, this physiological mechanism has multiple manifestations that range from impaired clearance of unfolded proteins to altered mitochondrial dynamics and apoptosis. While connections between t...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-016-0788-z
更新日期:2017-01-23 00:00:00
abstract::The NLRP3 (nucleotide-binding oligomerization domain-like receptor [NLR] family pyrin domain-containing 3) inflammasome is a member of the NLR family of innate immune cell sensors. These are crucial regulators of cytokine secretions, which promote ischemic cell death and insulin resistance. This review summarizes rece...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章,评审
doi:10.1186/s12974-019-1498-0
更新日期:2019-06-07 00:00:00
abstract:BACKGROUND:Ischemic stroke is a devastating disease without a cure. The available treatments for ischemic stroke, thrombolysis by tissue plasminogen activator, and thrombectomy are suitable only to a fraction of patients and thus novel therapeutic approaches are urgently needed. The neuroinflammatory responses elicited...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-020-01870-w
更新日期:2020-06-19 00:00:00
abstract:BACKGROUND:Ischemic stroke is a leading cause of disability worldwide and characteristically accompanied by downregulation of the Wnt/β-catenin signaling. Activation of Wnt/β-catenin signaling emerges to attenuate neuroinflammation after ischemic stroke; however, its effect on modulating microglial polarization is larg...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-019-1660-8
更新日期:2019-12-06 00:00:00
abstract:BACKGROUND:Microglial activation and the subsequent inflammatory response in the central nervous system play important roles in secondary damage after traumatic brain injury (TBI). High-mobility group box 1 (HMGB1) protein, an important mediator in late inflammatory responses, interacts with transmembrane receptor for ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-017-0917-3
更新日期:2017-07-24 00:00:00
abstract:BACKGROUND:Although evidence suggests that the prevalence of Parkinson's disease (PD) is lower in smokers than in non-smokers, the mechanisms of nicotine-induced neuroprotection remain unclear. Stimulation of the α7 nicotinic acetylcholine receptor (α7-nAChR) seems to be a crucial mechanism underlying the anti-inflamma...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-9-98
更新日期:2012-05-24 00:00:00
abstract:BACKGROUND:Kainic acid (KA)-induced status epilepticus (SE) was involved with release of free radicals. Sesamin is a well-known antioxidant from sesame seeds and it scavenges free radicals in several brain injury models. However the neuroprotective mechanism of sesamin to KA-induced seizure has not been studied. METHO...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-8-57
更新日期:2011-05-24 00:00:00
abstract::The role of inflammation in Alzheimer's disease (AD) has been controversial since its first consideration. As with most instances of neuroinflammation, the possibility must be considered that activation of glia and cytokine networks in AD arises merely as a reaction to neurodegeneration. Active, healthy neurons produc...
journal_title:Journal of neuroinflammation
pub_type: 社论
doi:10.1186/1742-2094-2-2
更新日期:2005-01-11 00:00:00
abstract:BACKGROUND:The collective cognitive and motor deficits known as HIV-associated neurocognitive disorders (HAND) remain high even among HIV+ individuals whose antiretroviral therapy is optimized. HAND is worsened in the context of opiate abuse. The mechanism of exacerbation remains unclear but likely involves chronic imm...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-018-1320-4
更新日期:2018-10-10 00:00:00
abstract:BACKGROUND:The chemokine interleukin-8 (IL-8) and its receptor CXCR2 contribute to chemotactic responses in Alzheimer's disease (AD); however, properties of the ligand and receptor have not been characterized in animal models of disease. The primary aim of our study was to examine effects of pharmacological antagonism ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-015-0339-z
更新日期:2015-08-09 00:00:00
abstract:BACKGROUND:Alzheimer's disease (AD) is characterized by extracellular β-amyloid (Aβ) plaques, neurofibrillary tangles (NFTs), and microglia-dominated neuroinflammation. The Nogo/NgR signal pathway is involved in AD pathological features, but the detailed mechanism needs further investigation. Our previous studies have ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-016-0522-x
更新日期:2016-03-03 00:00:00
abstract:BACKGROUND:The recruitment of immune system cells into the central nervous system (CNS) has a profound effect on the outcomes of injury and disease. Glia-derived chemoattractants, including chemokines, play a pivotal role in this process. In addition, cytokines and chemokines influence the phenotype of infiltrating imm...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-020-01748-x
更新日期:2020-02-25 00:00:00
abstract::Secretory phospholipase A2-IIA (sPLA2-IIA) is an inflammatory protein known to play a role in the pathogenesis of many inflammatory diseases. Although this enzyme has also been implicated in the pathogenesis of neurodegenerative diseases, there has not been a direct demonstration of its expression in diseased human br...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-3-28
更新日期:2006-10-07 00:00:00
abstract:BACKGROUND:Local and systemic inflammatory responses are initiated early after traumatic brain injury (TBI), and may play a key role in the secondary injury processes resulting in neuronal loss and neurological deficits. However, the mechanisms responsible for the rapid expansion of neuroinflammation and its long-term ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-017-0819-4
更新日期:2017-03-15 00:00:00
abstract:BACKGROUND:Preconditioning is a phenomenon by which tolerance develops to injury by previous exposure to a stressor of mild severity. Previous studies have shown that single or repeated low dose MDMA can attenuate 5-HT transporter loss produced by a subsequent neurotoxic dose of the drug. We have explored the mechanism...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-8-165
更新日期:2011-11-24 00:00:00
abstract:BACKGROUND AND PURPOSE:Inflammatory reaction plays a crucial role in cerebral ischemia reperfusion (IR) injury. It has been shown that activated microglia long-term existed in cerebral ischemia and induced second injury. Therefore, we hypothesize that prepared phosphatidylserine (PS)-modified microbubbles (PS-MBs) comb...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-018-1368-1
更新日期:2018-11-30 00:00:00
abstract:BACKGROUND:Cyclooxygenase-2 (COX-2), which is rapidly upregulated by inflammation, is a key enzyme catalyzing the rate-limiting step in the synthesis of several inflammatory prostanoids. Successful positron emission tomography (PET) radioligand imaging of COX-2 in vivo could be a potentially powerful tool for assessing...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-020-01804-6
更新日期:2020-05-02 00:00:00
abstract:BACKGROUND:Over the past decades, positron emission tomography (PET) imaging has become an increasingly useful research modality in the field of multiple sclerosis (MS) research, as PET can visualise molecular processes, such as neuroinflammation, in vivo. The second generation PET radioligand [18F]DPA714 binds with hi...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-018-1352-9
更新日期:2018-11-13 00:00:00
abstract:BACKGROUND:Cardiovascular diseases, including heart failure, are the most common cause of death globally. Recent studies support a high degree of comorbidity between heart failure and cognitive and mood disorders resulting in memory loss, depression, and anxiety. While neuroinflammation in the hypothalamic paraventricu...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-020-01892-4
更新日期:2020-07-23 00:00:00
abstract:BACKGROUND:The proteasome is a multisubunit enzyme complex involved in protein degradation, which is essential for many cellular processes. During inflammation, the constitutive subunits are replaced by their inducible counterparts, resulting in the formation of the immunoproteasome. METHODS:We investigated the expres...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-016-0662-z
更新日期:2016-08-26 00:00:00
abstract:BACKGROUND:Low testosterone and obesity are independent risk factors for dysfunction of the nervous system including neurodegenerative disorders such as Alzheimer's disease (AD). In this study, we investigate the independent and cooperative interactions of testosterone and diet-induced obesity on metabolic, inflammator...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-014-0162-y
更新日期:2014-09-16 00:00:00
abstract:BACKGROUND:Multiple sclerosis is a neuroinflammatory demyelinating and neurodegenerative disease of the central nervous system characterized by recurrent and progressive demyelination/remyelination cycles, neuroinflammation, oligodendrocyte loss, demyelination, and axonal degeneration. Cyclic phosphatidic acid (cPA) is...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-017-0923-5
更新日期:2017-07-21 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: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