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Microglia inflammation induces pro-inflammatory cytokines and pro-inflammatory enzymes expression, thus leading to inflammation-mediated neuronal cell death. Increased intracellular glycolysis participates in LPS-mediated microglia inflammation. Dexmedetomidine exhibits neuro-protective effects in some situations. In this study, we mainly focused on whether and how dexmedetomidine inhibits LPS-mediated cellular glycolysis and inflammation in BV2 cells. LPS induced pro-inflammatory cytokines and pro-inflammatory enzymes expression, and increased glycolysis capacity in BV2 cells. Moreover, inhibition of glycolysis by 2DG attenuated LPS-induced pro-inflammatory cytokines and pro-inflammatory enzymes expression. Moreover, LPS upregulated hypoxia-inducible factor 1α (HIF1α) expression and decreased sirt1 expression. Dexmedetomidine counteracted these effects induced by LPS. Further, 2-methoxyestradiol, a HIF1α inhibitor, could inhibit LPS-mediated glycolysis and inflammation in BV2 cells, which was similar to the effects of dexmedetomidine. In addition, these effects of dexmedetomidine could be reversed by EX527, a sirt1 inhibitor. The present study indicated that dexmedetomidine via up-regulation of sirt1 expression, inhibited HIF-1α expression and glycolysis, thus reducing LPS-mediated inflammation in BV2 cells.
This article was published in the following journal.
Name: Fundamental & clinical pharmacology
Mounting evidence suggests that lysosome dysfunction promotes the progression of several neurodegenerative diseases via hampering autophagy flux. While regulation of autophagy in microglia may affect ...
Hyperbaric oxygen preconditioning (HBOP) attenuates brain edema, microglia activation, and inflammation after intracerebral hemorrhage (ICH). In this present study, we investigated the role of HBOP in...
Microglia/macrophage mediated-inflammation, a main contributor to the microenvironment after spinal cord injury (SCI), persists for a long period of time and affects SCI repair. However, the effects o...
In this study, we investigated whether the neuroprotective efficacy of EGCG was mediated by inhibition of canonical and non-canonical inflammasome activation via TLR4/NF-κB pathway both in LPS+Aβ-i...
Aerobic glycolysis promotes metastasis and correlates with poorer clinical outcomes in hepatocellular carcinoma (HCC), but the controllers and mechanisms of abnormally activated glycolysis remain uncl...
In a number of neuropsychiatric disorders such as depression, both brain inflammation and glutamate mediated excitotoxicity (cell death through over-activated stimulation) are suspected to...
Dexmedetomidine, was reported to prevent postoperative delirium in elderly patients following its use in intensive care units. Possible mechanisms included improved quality of sleep and an...
Dexmedetomidine is widely used as an anaesthetic for general anesthesia during surgery. Previous studies in cells and animals show that dexmedetomidine may promote cancer growth. Using ser...
Many studies have shown that inflammation has an important effect on the development, progression, and also response to treatment of tumors. Dexmedetomidine is a potent and selective alpha...
Dexmedetomidine may alter whole blood coagulation. However, little is known about the dose-response relationships according to the blood concentration of dexmedetomidine. The investigators...
The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activa
An anti-CTLA-4 ANTIGEN monoclonal antibody initially indicated for the treatment of certain types of metastatic MELANOMA. Its mode of actions may include blocking of CTLA-4 mediated inhibition of CYTOTOXIC T LYMPHOCYTES, allowing for more efficient destruction of target tumor cells.
Phenomenon of cell-mediated immunity measured by in vitro inhibition of the migration or phagocytosis of antigen-stimulated LEUKOCYTES or MACROPHAGES. Specific CELL MIGRATION ASSAYS have been developed to estimate levels of migration inhibitory factors, immune reactivity against tumor-associated antigens, and immunosuppressive effects of infectious microorganisms.
Mononuclear cells with pronounced phagocytic ability that are distributed extensively in lymphoid and other organs. It includes MACROPHAGES and their precursors; PHAGOCYTES; KUPFFER CELLS; HISTIOCYTES; DENDRITIC CELLS; LANGERHANS CELLS; and MICROGLIA. The term mononuclear phagocyte system has replaced the former reticuloendothelial system, which also included less active phagocytic cells such as fibroblasts and endothelial cells. (From Illustrated Dictionary of Immunology, 2d ed.)
Biological therapy involves the use of living organisms, substances derived from living organisms, or laboratory-produced versions of such substances to treat disease. Some biological therapies for cancer use vaccines or bacteria to stimulate the body&rs...
Neurology - Central Nervous System (CNS)
Alzheimer's Disease Anesthesia Anxiety Disorders Autism Bipolar Disorders Dementia Epilepsy Multiple Sclerosis (MS) Neurology Pain Parkinson's Disease Sleep Disorders Neurology is the branch of me...