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https://www.readbyqxmd.com/read/29325899/do-ketone-bodies-mediate-the-anti-seizure-effects-of-the-ketogenic-diet
#1
REVIEW
Timothy A Simeone, Kristina A Simeone, Carl E Stafstrom, Jong M Rho
Although the mechanisms underlying the anti-seizure effects of the high-fat ketogenic diet (KD) remain unclear, a long-standing question has been whether ketone bodies (i.e., beta-hydroxybutyrate [BHB], acetoacetate [ACA] and acetone), either alone or in combination, contribute mechanistically. The traditional belief has been that while ketone bodies reflect enhanced fatty acid oxidation and a general shift toward intermediary metabolism, they are not likely to be the key mediators of the KD's clinical effects, as blood levels of BHB do not correlate consistently with improved seizure control...
January 8, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29318480/rosmarinic-acid-mitigates-lipopolysaccharide-induced-neuroinflammatory-responses-through-the-inhibition-of-tlr4-and-cd14-expression-and-nf-%C3%AE%C2%BAb-and-nlrp3-inflammasome-activation
#2
Yicong Wei, Jianxiong Chen, Yonghong Hu, Wei Lu, Xiaoqin Zhang, Ruiguo Wang, Kedan Chu
The excessive activation of microglia plays a key role in the pathogenesis of neurodegenerative diseases. The neuroprotective properties of rosmarinic acid have been reported in a variety of disease models both in vitro and in vivo; however, the mechanism underlying its anti-neuroinflammatory activity has not been clearly elucidated. In the present study, we evaluated the anti-inflammatory effects of rosmarinic acid in conditions of neuroinflammatory injury in vitro and in vivo. The results indicated that rosmarinic acid reduced the expression of CD11b, a marker of microglia and macrophages, in the brain and dramatically inhibited the levels of inflammatory cytokines and mediators, such as TNFα, IL-6, IL-1β, COX-2, and iNOS, in a dose-dependent manner both in vitro and in vivo...
January 9, 2018: Inflammation
https://www.readbyqxmd.com/read/29317641/zika-virus-infection-induces-host-inflammatory-responses-by-facilitating-nlrp3-inflammasome-assembly-and-interleukin-1%C3%AE-secretion
#3
Wenbiao Wang, Geng Li, De Wu, Zhen Luo, Pan Pan, Mingfu Tian, Yingchong Wang, Feng Xiao, Aixin Li, Kailang Wu, Xiaohong Liu, Lang Rao, Fang Liu, Yingle Liu, Jianguo Wu
Zika virus (ZIKV) infection is a public health emergency and host innate immunity is essential for the control of virus infection. The NLRP3 inflammasome plays a key role in host innate immune responses by activating caspase-1 to facilitate interleukin-1β (IL-1β) secretion. Here we report that ZIKV stimulates IL-1β secretion in infected patients, human PBMCs and macrophages, mice, and mice BMDCs. The knockdown of NLRP3 in cells and knockout of NLRP3 in mice inhibit ZIKV-mediated IL-1β secretion, indicating an essential role for NLRP3 in ZIKV-induced IL-1β activation...
January 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29306934/gliotransmitters-and-cytokines-in-the-control-of-blood-brain-barrier-permeability
#4
REVIEW
Elena D Osipova, Oxana V Semyachkina-Glushkovskaya, Andrey V Morgun, Natalia V Pisareva, Natalia A Malinovskaya, Elizaveta B Boitsova, Elena A Pozhilenkova, Olga A Belova, Vladimir V Salmin, Tatiana E Taranushenko, Mami Noda, Alla B Salmina
The contribution of astrocytes and microglia to the regulation of neuroplasticity or neurovascular unit (NVU) is based on the coordinated secretion of gliotransmitters and cytokines and the release and uptake of metabolites. Blood-brain barrier (BBB) integrity and angiogenesis are influenced by perivascular cells contacting with the abluminal side of brain microvessel endothelial cells (pericytes, astrocytes) or by immune cells existing (microglia) or invading the NVU (macrophages) under pathologic conditions...
January 8, 2018: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/29301581/activation-of-dopamine-d1-receptor-decreased-nlrp3-mediated-inflammation-in-intracerebral-hemorrhage-mice
#5
Tian Wang, Derek Nowrangi, Lingyan Yu, Tai Lu, Jiping Tang, Bing Han, Yuxin Ding, Fenghua Fu, John H Zhang
BACKGROUND: Inflammasomes are involved in diverse inflammatory diseases. Previous study reported that the neurotransmitter dopamine inhibited NLRP3 inflammasome activation via dopamine D1 receptor (DRD1). The present study aims to investigate the role of DRD1 on neuroinflammation in intracerebral hemorrhage (ICH) mice and the potential mechanism mediated by NLRP3 inhibition. METHODS: One hundred and six male CD-1 mice were subjected to intrastriatal injection of bacterial collagenase or PBS...
January 4, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29295651/mcc950-the-selective-nlrp3-inflammasome-inhibitor-protects-mice-against-traumatic-brain-injury
#6
Saifudeen Ismael, Sanaz Nasoohi, Tauheed Ishrat
NNucleotide oligomerization domain (NOD)-like receptor protein-3 (NLRP3) inflammasome may intimately contribute to sustaining damage following traumatic brain injury (TBI). This study aims to examine whether specific modulation of NLPR3 inflammasome by MCC950, a novel selective NLRP3 inhibitor confers protection after experimental TBI. Unilateral cortical impact injury was induced in young adult C57BL/6 mice. MCC950 (50 mg/kg, i.p.) or saline was administration at 1 h and 3 h post TBI. Animals were tested for neurological function, and then sacrificed for edema at 24 or 72 h post TBI...
January 2, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29290552/microglial-ramification-surveillance-and-interleukin-1%C3%AE-release-are-regulated-by-the-two-pore-domain-k-channel-thik-1
#7
Christian Madry, Vasiliki Kyrargyri, I Lorena Arancibia-Cárcamo, Renaud Jolivet, Shinichi Kohsaka, Robert M Bryan, David Attwell
Microglia exhibit two modes of motility: they constantly extend and retract their processes to survey the brain, but they also send out targeted processes to envelop sites of tissue damage. We now show that these motility modes differ mechanistically. We identify the two-pore domain channel THIK-1 as the main K+ channel expressed in microglia in situ. THIK-1 is tonically active, and its activity is potentiated by P2Y12 receptors. Inhibiting THIK-1 function pharmacologically or by gene knockout depolarizes microglia, which decreases microglial ramification and thus reduces surveillance, whereas blocking P2Y12 receptors does not affect membrane potential, ramification, or surveillance...
December 27, 2017: Neuron
https://www.readbyqxmd.com/read/29273951/neuroinflammatory-responses-in-alzheimer-s-disease
#8
REVIEW
Cira Dansokho, Michael Thomas Heneka
Neuroinflammatory responses in Alzheimer's disease (AD) are complex and not fully understood. They involve various cellular and molecular players and associate interaction between the central nervous system (CNS) and the periphery. Amyloid peptides within the senile plaques and abnormally phosphorylated tau in neurofibrillary tangles are able to initiate inflammatory responses, in brain of AD patients and in mouse models of this disease. The outcome of these responses on the pathophysiology of AD depends on several factors and can be either beneficial or detrimental...
December 22, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29273596/dihydrolipoic-acid-inhibits-lysosomal-rupture-and-nlrp3-through-lysosome-associated-membrane-protein-1-calcium-calmodulin-dependent-protein-kinase-ii-tak1-pathways-after-subarachnoid-hemorrhage-in-rat
#9
Keren Zhou, Budbazar Enkhjargal, Zhiyi Xie, Chengmei Sun, Lingyun Wu, Jay Malaguit, Sheng Chen, Jiping Tang, Jianmin Zhang, John H Zhang
BACKGROUND AND PURPOSE: The NLRP3 (nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3) inflammasome is a crucial component of the inflammatory response in early brain injury after subarachnoid hemorrhage (SAH). In this study, we investigated a role of dihydrolipoic acid (DHLA) in lysosomal rupture, NLRP3 activation, and determined the underlying pathway. METHODS: SAH was induced by endovascular perforation in male Sprague-Dawley rats...
January 2018: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/29251706/valproic-acid-induces-pro-survival-transcriptomic-changes-in-swine-subjected-to-traumatic-injury-and-hemorrhagic-shock
#10
Patrick E Georgoff, Vahagn C Nikolian, Gerald Higgins, Kiril Chtraklin, Hassan Eidy, Mohamed H Ghandour, Aaron Williams, Brian Athey, Hasan B Alam
BACKGROUND: Valproic acid (VPA) is a histone deacetylase inhibitor that improves outcomes in large animal models of trauma. However, its protective mechanism of action is not completely understood. We sought to characterize the genetic changes induced by VPA treatment following traumatic injuries. METHODS: Six female Yorkshire swine were subjected to traumatic brain injury (TBI, controlled cortical impact), polytrauma (liver and splenic laceration, rib fracture, rectus crush), and hemorrhagic shock (HS, 40% total blood volume)...
December 14, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/29236160/ethanol-and-cytokines-in-the-central-nervous-system
#11
Marisa Roberto, Reesha R Patel, Michal Bajo
The innate immune system plays a critical role in the ethanol-induced neuroimmune response in the brain. Ethanol initiates the innate immune response via activation of the innate immune receptors Toll-like receptors (TLRs, e.g., TLR4, TLR3, TLR7) and NOD-like receptors (inflammasome NLRs) leading to a release of a plethora of chemokines and cytokines and development of the innate immune response. Cytokines and chemokines can have pro- or anti-inflammatory properties through which they regulate the immune response...
December 14, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29222907/the-ameliorative-effect-of-fluoxetine-on-neuroinflammation-induced-by-sleep-deprivation
#12
Maosheng Xia, Xiaowei Li, Li Yang, Jiaan Ren, Guangfeng Sun, Shuang Qi, Alexei Verkhratsky, Baoman Li
It is well known that sleep disorders are harmful to people's health and performance, and growing evidence suggests that sleep deprivation (SD) can trigger neuroinflammation in the brain. The nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome is reported to be relevant to the neuroinflammation induced by SD, but the regulatory signaling that governs the NLRP3 inflammasome in SD is still unknown. Meanwhile, whether the regulatory action of antidepressants in astrocytes could affect the neuroinflammation induced by SD also remains obscure...
December 9, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29219210/bioenergetic-regulation-of-microglia
#13
REVIEW
Soumitra Ghosh, Erika Castillo, Elma S Frias, Raymond A Swanson
Microglia have diverse actions, ranging from synapse pruning in development to cytotoxic effects in disease. Brain energy metabolism and substrate availability vary under normal and disease states, but how these variations influence microglial function is relatively unknown. Microglia, like most other cell types, express the full complement of gene products required for both glycolytic and oxidative metabolism. Evidence suggests that microglia increase aerobic glycolysis and decrease respiration when activated by various stimuli...
December 8, 2017: Glia
https://www.readbyqxmd.com/read/29212744/selective-nlrp3-pyrin-domain-containing-protein-3-inflammasome-inhibitor-reduces-brain-injury-after-intracerebral-hemorrhage
#14
Honglei Ren, Ying Kong, Zhijia Liu, Dongyun Zang, Xiaoxia Yang, Kristofer Wood, Minshu Li, Qiang Liu
BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is a devastating disease without effective treatment. As a key component of the innate immune system, the NOD-like receptor (NLR) family, NLRP3 (pyrin domain-containing protein 3) inflammasome, when activated after ICH, promotes neuroinflammation and brain edema. MCC950 is a potent, selective, small-molecule NLRP3 inhibitor that blocks NLRP3 activation at nanomolar concentrations. Here, we examined the effect of MCC950 on brain injury and inflammation in 2 models of ICH in mice...
December 6, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/29207113/spontaneous-hypothermia-ameliorated-inflammation-and-neurologic-deficit-in-rat-cardiac-arrest-models-following-resuscitation
#15
Minggen Zhou, Peng Wang, Zhengfei Yang, Haidong Wu, Zitong Huan
Cardiac arrest (CA) is a leading cause of mortality worldwide. The majority of the associated mortalities are caused by post‑CA syndrome, which includes symptoms, such as neurologic damage, myocardial dysfunction and systemic inflammation. Following CA, return of spontaneous circulation (ROSC) leads to a brain reperfusion injury, which subsequently causes adverse neurologic outcomes or mortality. Therefore, investigating the underlying mechanisms of ROSC‑induced neurologic deficits and establishing potential treatments is critical to prevent and treat post‑CA syndrome...
November 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29175152/transplantation-of-human-umbilical-cord-blood-mononuclear-cells-attenuated-ischemic-injury-in-mcao-rats-via-inhibition-of-nf-%C3%AE%C2%BAb-andnlrp3inflammasome
#16
Lu Liu, Juan Cen, Yong Man, Jianbin Li, Dahuan Zhang, Fei Wang, Jinhua Li, Ji Ma, Xiaoming Wang, Biansheng Ji
Accumulated evidences displayed that transplantation of stem cells may be a promising approach for the treatment of neurological disorders. However, the underlying mechanisms remain to be well elucidated. Moreover, some investigators can not reproduce similar results as the previous. The present results showed that transplantation of fresh human umbilical cord blood mononuclear cells (cbMNCs) attenuated ischemic damage in middle cerebral artery occlusion (MCAO) rats, accompanied with improvement of neurologic deficits, learning and memory function...
November 23, 2017: Neuroscience
https://www.readbyqxmd.com/read/29173188/innate-immune-surveillance-in-the-central-nervous-system-in-legionella-pneumophila-infection
#17
Pasqualina Lagana, Luca Soraci, Maria Elsa Gambuzza, Santi Delia
Innate immune response represents a common event in many neuroinflammatory diseases. The resident immune cells of the central nervous system (CNS) are capable of sensing and reacting to both infections and sterile trauma. Peripheral immune cell migration into CNS is regulated by the blood-brain barrier (BBB), although peripheral immune cells can invade CNS through meninges, choroid plexus, perivascular spaces, and cerebrospinal fluid. Consequently, in the brain immune reactions can be mediated by both resident and peripheral immune cells...
November 23, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/29163015/resveratrol-attenuates-early-brain-injury-after-experimental-subarachnoid-hemorrhage-via-inhibition-of-nlrp3-inflammasome-activation
#18
Xiangsheng Zhang, Qi Wu, Qingrong Zhang, Yue Lu, Jingpeng Liu, Wei Li, Shengyin Lv, Mengliang Zhou, Xin Zhang, Chunhua Hang
Previous studies have demonstrated resveratrol (RSV) has beneficial effects in early brain injury (EBI) after subarachnoid hemorrhage (SAH). However, the beneficial effects of RSV and the underlying mechanisms have not been clearly identified. The nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation plays a crucial role in the EBI pathogenesis. The aim of this study was to investigate the role of RSV on the NLRP3 inflammasome signaling pathway and EBI in rats after SAH...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29150951/inflammasome-its-role-in-traumatic-brain-and-spinal-cord-injury
#19
REVIEW
Keywan Mortezaee, Neda Khanlarkhani, Cordian Beyer, Adib Zendedel
Traumatic brain injury (TBI) and spinal cord injury (SCI) are pathological events that lead to neuropathological conditions which have in consequence the initiation of pro-inflammatory cytokine production. Neuroinflammation plays a key role in the secondary phase of both TBI and SCI after initial cell death. Activation of cytoplasmic inflammasome complexes is regarded as the essential step of neuroinflammation and a key trigger for neuronal death called pyroptosis. Inflammasome complexes are involved in activation of caspase-1 which catalyzes the cleavage of pro-interleukins into their active forms (including interleukin-18 (IL-18) and IL-1β)...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29067455/hyperbaric-oxygen-alleviates-the-activation-of-nlrp%C3%A2-3%C3%A2-inflammasomes-in-traumatic-brain-injury
#20
Huihui Qian, Qinghe Li, Woda Shi
Growing evidence has demonstrated that the nucleotide‑binding oligomerization domain‑like receptor family pyrin domain containing 3 (NLRP‑3) inflammasome‑mediated inflammatory pathways have been involved in the secondary injury of traumatic brain injury (TBI). In the present study, the authors investigated the effects of hyperbaric oxygen (HBO) therapy on the NLRP‑3 inflammasome pathway following TBI. Following the evaluation of motor deficits and brain edema, the therapeutic effects of HBO on interleukin (IL)‑1β and IL‑18 expression were assessed, as well as NLRP‑3 inflammasome activation following TBI...
October 2017: Molecular Medicine Reports
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