The ameliorative effects of a hypnotic bromvalerylurea in sepsis

Kikuchi, Satoshi; Nishihara, Tasuku; Kawasaki, Shun; Abe, Naoki; Kuwabara, Jun; Choudhury, Mohammed E.; Takahashi, Hiroyuki; Yano, Hajime; Nagaro, Takumi; Watanabe, Yuji; Aibiki, Mayuki; Tanaka, Junya

doi:10.1016/j.bbrc.2015.02.111

Cited by 14 publications

(13 citation statements)

References 33 publications

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“…BU has marked antiinflammatory effects on microglia (Higaki et al, ) and macrophages (Kikuchi et al, ), and the effects that are at least partly attributable to suppressive effects on ATP synthesis (Kawasaki et al, ). In this study, the effects of BU on cell metabolism were investigated in primary microglial cells (Figure ) and alveolar macrophages (Supporting Information Figure S1) using the Seahorse Mito‐Stress Test, which assesses Oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) (Figure a) (Banh et al, ; Garaude et al, ).…”

Section: Resultsmentioning

confidence: 99%

“…Oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were investigated to evaluate mitochondrial respiration and glycolysis, respectively, in rat primary microglial cells and alveolar macrophages using XFp Extracellular Flux Analyzer (Agilent Seahorse Bioscience, Santa Clara, CA) (Banh et al, ; Garaude et al, ). Rat alveolar macrophages, prepared as described elsewhere (Kikuchi et al, ), or microglial cells were seeded in E2 at 2.5 × 10 4 cells in eight‐well plates provided by the manufacturer. Two wells among the eight well were used as blank wells.…”

Section: Methodsmentioning

confidence: 99%

“…We have previously found marked anti‐inflammatory effects of an established hypnotic/sedative, bromovalerylurea (BU; C 6 H 11 BrN 2 O 2 , CAS: 496‐67‐3) (Higaki et al, ; Kikuchi et al, ). BU inhibits CCL2 expression by lipopolysaccharide (LPS)‐treated peritoneal macrophages (Kikuchi et al, ) and proinflammatory activation of microglia (Higaki et al, ). The antiinflammatory effects were at least partly attributable to its suppressive effects on mitochondrial ATP production (Kawasaki et al, ).…”

Section: Introductionmentioning

confidence: 99%

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Comparison of the detrimental features of microglia and infiltrated macrophages in traumatic brain injury: A study using a hypnotic bromovalerylurea

Abe

Choudhury

Watanabe

et al. 2018

Glia

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Microglia and blood-borne macrophages in injured or diseased brains are difficult to distinguish because they share many common characteristics. However, the identification of microglia-specific markers and the use of flow cytometry have recently made it easy to discriminate these types of cells. In this study, we analyzed the features of blood-borne macrophages, and activated and resting microglia in a rat traumatic brain injury (TBI) model. Oxidative injury was indicated in macrophages and neurons in TBI lesions by the presence of 8-hydroxy-2'-deoxyguanosine (8-OHdG). Generation of mitochondrial reactive oxygen species (ROS) was markedly observed in granulocytes and macrophages, but not in activated or resting microglia. Dihydroethidium staining supported microglia not being the major source of ROS in TBI lesions. Furthermore, macrophages expressed NADPH oxidase 2, interleukin-1β (IL-1β), and CD68 at higher levels than microglia. In contrast, microglia expressed transforming growth factor β1 (TGFβ1), interleukin-6 (IL-6), and tumor necrosis factor α at higher levels than macrophages. A hypnotic, bromovalerylurea (BU), which has anti-inflammatory effects, reduced both glycolysis and mitochondrial oxygen consumption. BU administration inhibited chemokine CCL2 expression, accumulation of monocytes/macrophages, 8-OHdG generation, mitochondrial ROS generation, and proinflammatory cytokine expression, and markedly ameliorated the outcome of the TBI model. Yet, BU did not inhibit microglial activation or expression of TGFβ1 and insulin-like growth factor 1 (IGF-1). These results indicate that macrophages are the major aggravating cell type in TBI lesions, in particular during the acute phase. Activated microglia may even play favorable roles. Reduction of cellular energy metabolism in macrophages and suppression of CCL2 expression in injured tissue may lead to amelioration of TBI.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Comparison of the detrimental features of microglia and infiltrated macrophages in traumatic brain injury: A study using a hypnotic bromovalerylurea

Abe

Choudhury

Watanabe

et al. 2018

Glia

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“…BU prevented the death of rats with cecum ligation and puncture-induced sepsis by suppressing the proinflammatory activation of peritoneal macrophages [97] . Oral administration of BU ameliorated PD in rat models while inhibiting the expression of proinflammatory mediators in the ventral midbrain [43] .…”

Section: Bromovalerylureamentioning

confidence: 99%

“…It is not prescribed currently because of its weak actions as a hypnotic/sedative compared with newer agents such as benzodiazepines and also due to dependency. Recently, it has been found to have strong anti-inflammatory effects [10,43,96,97] . The effects of BU on LPS-treated primary rat microglia are as strong as those of Dex [43] .…”

Section: Bromovalerylureamentioning

confidence: 99%

Favorable and unfavorable roles of microglia and macrophages in the pathologic central nervous system

Tanaka¹

2020

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How to cite this article: Tanaka J. Favorable and unfavorable roles of microglia and macrophages in the pathologic central nervous system. Neuroimmunol Neuroinflammation 2020;7:73-91. http://dx. AbstractResident microglia in the central nervous system (CNS) are activated rapidly in response to even minor pathologic changes in the CNS, releasing various cytokines, growth factors, reactive oxygen species and other bioactive substances, in addition to eliminating synapses and degenerating cells through phagocytosis. Monocytes in circulation invade the inflamed brain tissues and develop into macrophages that also produce several bioactive substances and engage in phagocytosis. This article introduces methods for distinguishing microglia and macrophages. The pathophysiological roles of resident microglia and macrophages are discussed in animal models with neuroinflammation in the brain either with or without disruption of the blood-brain barrier. Both cell types have ameliorating and aggravating effects on the pathologic CNS, and their different roles are addressed in this article. Furthermore, this article compares the effects of some pharmacological interventions to induce phenotypic cellular changes for improved outcomes of the pathologic CNS.

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CLOCK modulates survival and acute lung injury in mice with polymicrobial sepsis

Wang

Hsieh

et al. 2016

Biochemical and Biophysical Research Communications

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The ameliorative effects of a hypnotic bromvalerylurea in sepsis

Cited by 14 publications

References 33 publications

Comparison of the detrimental features of microglia and infiltrated macrophages in traumatic brain injury: A study using a hypnotic bromovalerylurea

Comparison of the detrimental features of microglia and infiltrated macrophages in traumatic brain injury: A study using a hypnotic bromovalerylurea

Favorable and unfavorable roles of microglia and macrophages in the pathologic central nervous system

CLOCK modulates survival and acute lung injury in mice with polymicrobial sepsis

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