Intestinal ischemia/reperfusion enhances microglial activation and induces cerebral injury and memory dysfunction in rats*

Zhou, Jun; Huang, Wenqi; Cai, Li; Wu, Guiyun; Li, Yunsheng; Wen, Sijian; Lei, Wanlong; Liu, Ke-Xuan

doi:10.1097/ccm.0b013e3182546855

Cited by 69 publications

(76 citation statements)

References 43 publications

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“…The model of intestinal I/R was established as previously reported 27. During the study period, body temperature was maintained at 37°C with the aid of a heating blanket.…”

Section: Methodsmentioning

confidence: 99%

Necroptosis is a key mediator of enterocytes loss in intestinal ischaemia/reperfusion injury

Wen

Ling

Yang

et al. 2016

J Cellular Molecular Medi

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Cell death is an important biological process that is believed to have a central role in intestinal ischaemia/reperfusion (I/R) injury. While the apoptosis inhibition is pivotal in preventing intestinal I/R, how necrotic cell death is regulated remains unknown. Necroptosis represents a newly discovered form of programmed cell death that combines the features of both apoptosis and necrosis, and it has been implicated in the development of a range of inflammatory diseases. Here, we show that receptor‐interacting protein 1/3 (RIP1/3) kinase and mixed lineage kinase domain‐like protein recruitment mediates necroptosis in a rat model of ischaemic intestinal injury in vivo. Furthermore, necroptosis was specifically blocked by the RIP1 kinase inhibitor necrostatin‐1. In addition, the combined treatment of necrostatin‐1 and the pan‐caspase inhibitor Z‐VAD acted synergistically to protect against intestinal I/R injury, and these two pathways can be converted to one another when one is inhibited. In vitro, necrostatin‐1 pre‐treatment reduced the necroptotic death of oxygen‐glucose deprivation challenged intestinal epithelial cell‐6 cells, which in turn dampened the production of pro‐inflammatory cytokines (tumour necrosis factor‐α and interleukin‐1β), and suppressed high‐mobility group box‐1 (HMGB1) translocation from the nucleus to the cytoplasm and the subsequent release of HMGB1 into the supernatant, thus decreasing the activation of Toll‐like receptor 4 and the receptor for advanced glycation end products. Collectively, our study reveals a robust RIP1/RIP3‐dependent necroptosis pathway in intestinal I/R‐induced intestinal injury in vivo and in vitro and suggests that the HMGB1 signalling is highly involved in this process, making it a novel therapeutic target for acute ischaemic intestinal injury.

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“…The model of intestinal I/R was established as previously reported 27. During the study period, body temperature was maintained at 37°C with the aid of a heating blanket.…”

Section: Methodsmentioning

confidence: 99%

Necroptosis is a key mediator of enterocytes loss in intestinal ischaemia/reperfusion injury

Wen

Ling

Yang

et al. 2016

J Cellular Molecular Medi

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“…Animals were anesthetized with sevoflurane and were placed in a supine position with their paws taped to the operating table. The model of intestinal I/R was established as in our previous study (27). Briefly, the small intestine was exteriorized with a 1-cm midline laparotomy, and the superior mesenteric artery (SMA) was identified.…”

Section: Animal Modelmentioning

confidence: 99%

Treatment with Recombinant Trichinella spiralis Cathepsin B–like Protein Ameliorates Intestinal Ischemia/Reperfusion Injury in Mice by Promoting a Switch from M1 to M2 Macrophages

Liu

Wen

Zhan

et al. 2015

The Journal of Immunology

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Intestinal ischemia/reperfusion (I/R) injury, in which macrophages play a key role, can cause high morbidity and mortality. The switch from classically (M1) to alternatively (M2) activated macrophages, which is dependent on the activation of STAT6 signaling, has been shown to protect organs from I/R injuries. In the current study, the effects of recombinant Trichinella spiralis cathepsin B–like protein (rTsCPB) on intestinal I/R injury and the potential mechanism related to macrophage phenotypes switch were investigated. In a mouse I/R model undergoing 60-min intestinal ischemia followed by 2-h or 7-d reperfusion, we demonstrated that intestinal I/R caused significant intestinal injury and induced a switch from M2 to M1 macrophages, evidenced by a decrease in levels of M2 markers (arginase-1 and found in inflammatory zone protein), an increase in levels of M1 markers (inducible NO synthase and CCR7), and a decrease in the ratio of M2/M1 macrophages. RTsCPB reversed intestinal I/R-induced M2–M1 transition and promoted M1-M2 phenotype switch evidenced by a significant decrease in M1 markers, an increase in M2 markers, and the ratio of M2/M1 macrophages. Meanwhile, rTsCPB significantly ameliorated intestinal injury and improved intestinal function and survival rate of animals, accompanied by a decrease in neutrophil infiltration and an increase in cell proliferation in the intestine. However, a selective STAT6 inhibitor, AS1517499, reversed the protective effects of rTsCPB by inhibiting M1 to M2 transition. These findings suggest that intestinal I/R injury causes a switch from M2 to M1 macrophages and that rTsCPB ameliorates intestinal injury by promoting STAT6-dependent M1 to M2 transition.

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“…One essential step in the progression of brain diseases is neuroinflammation (1), for which proinflammatory cytokines play a central role (2). Recent work has shown that the pathogenesis of neuroinflammation is mediated in part by the release of adenosine or uridine derivatives from the damaged site, involving a family of ionotropic purinergic receptors (P2XRs) with elevated expression (3).…”

mentioning

confidence: 99%

Characterization of ¹¹C-GSK1482160 for Targeting the P2X7 Receptor as a Biomarker for Neuroinflammation

et al. 2016

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Intestinal ischemia/reperfusion enhances microglial activation and induces cerebral injury and memory dysfunction in rats*

Abstract: These findings indicate that intestinal ischemia/reperfusion-induced intestinal injury can lead to cerebral damage and memory dysfunction partly via microglia activation which further facilitates oxidative injury, inflammatory response, and neuronal cell apoptosis.

Cited by 69 publications

References 43 publications

Necroptosis is a key mediator of enterocytes loss in intestinal ischaemia/reperfusion injury

Necroptosis is a key mediator of enterocytes loss in intestinal ischaemia/reperfusion injury

Treatment with Recombinant Trichinella spiralis Cathepsin B–like Protein Ameliorates Intestinal Ischemia/Reperfusion Injury in Mice by Promoting a Switch from M1 to M2 Macrophages

Characterization of ¹¹C-GSK1482160 for Targeting the P2X7 Receptor as a Biomarker for Neuroinflammation

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Intestinal ischemia/reperfusion enhances microglial activation and induces cerebral injury and memory dysfunction in rats*

Abstract: These findings indicate that intestinal ischemia/reperfusion-induced intestinal injury can lead to cerebral damage and memory dysfunction partly via microglia activation which further facilitates oxidative injury, inflammatory response, and neuronal cell apoptosis.

Cited by 69 publications

References 43 publications

Necroptosis is a key mediator of enterocytes loss in intestinal ischaemia/reperfusion injury

Necroptosis is a key mediator of enterocytes loss in intestinal ischaemia/reperfusion injury

Treatment with Recombinant Trichinella spiralis Cathepsin B–like Protein Ameliorates Intestinal Ischemia/Reperfusion Injury in Mice by Promoting a Switch from M1 to M2 Macrophages

Characterization of 11C-GSK1482160 for Targeting the P2X7 Receptor as a Biomarker for Neuroinflammation

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Characterization of ¹¹C-GSK1482160 for Targeting the P2X7 Receptor as a Biomarker for Neuroinflammation