Early inflammatory damage to intestinal neurons occurs via inducible nitric oxide synthase

Venkataramana, Shriram; Lourenssen, Sandra; Miller, Kurtis G.; Blennerhassett, Michael G.

doi:10.1016/j.nbd.2014.12.014

Cited by 38 publications

(47 citation statements)

References 74 publications

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“…; Venkataramana et al . ). Neuroprotective roles of NO can be seen in vitro where addition of a NO donor promotes and addition of a NOS inhibitor attenuates survival of enteric neurons (Sandgren et al .…”

Section: Discussionmentioning

confidence: 97%

Focal, but not global, cerebral ischaemia causes loss of myenteric neurons and upregulation of vasoactive intestinal peptide in mouse ileum

Cheng

Svensson

Yang

et al. 2018

Int J Experimental Path

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Reduced blood flow to the brain induces cerebral ischaemia, potentially causing central injury and peripheral complications including gastrointestinal (GI) dysfunction. The pathophysiology behind GI symptoms is suspected to be neuropathy in the enteric nervous system (ENS), which is essential in regulating GI function. This study investigates if enteric neuropathy occurs after cerebral ischaemia, by analysing neuronal survival and relative numbers of vasoactive intestinal peptide (VIP) and neuronal nitric oxide synthase (nNOS) expressing neurons in mouse ileum after three types of cerebral ischaemia. Focal cerebral ischaemia, modelled by permanent middle cerebral artery occlusion (pMCAO) and global cerebral ischaemia, modelled with either transient occlusion of both common carotid arteries followed by reperfusion (GCIR) or chronic cerebral hypoperfusion (CCH) was performed on C56BL/6 mice. Sham-operated mice for each ischaemia model served as control. Ileum was collected after 1-17 weeks, depending on model, and analysed using morphometry and immunocytochemistry. For each group, intestinal mucosa and muscle layer thicknesses, neuronal numbers and relative proportions of neurons immunoreactive (IR) for nNOS or VIP were estimated. No alterations in mucosa or muscle layer thicknesses were noted in any of the groups. Loss of myenteric neurons and an increased number of VIP-IR submucous neurons were found in mouse ileum 7 days after pMCAO. None of the global ischaemia models showed any alterations in neuronal survival or relative numbers of VIP- and nNOS-IR neurons. We conclude that focal cerebral ischaemia and global cerebral ischaemia influence enteric neuronal survival differently. This is suggested to reflect differences in peripheral neuro-immune responses.

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Section: Discussionmentioning

confidence: 97%

Focal, but not global, cerebral ischaemia causes loss of myenteric neurons and upregulation of vasoactive intestinal peptide in mouse ileum

Cheng

Svensson

Yang

et al. 2018

Int J Experimental Path

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“…Therefore, the iNOS increase played an important role in inflammation-induced intestinal dysmotility in the CKD progression. However, the underlying mechanism for the iNOS increase was not investigated in the present study; but we speculate that there may be a feedback mechanism for this enzyme increase in response to uremic toxins' effect in the CKD progression [20]. Nevertheless, another study emphasizing the pathway about uremic toxins mediated iNOS activation is underway to explore the exact mechanism of the intestinal dysmotility in the CKD progression.…”

Section: Discussionmentioning

confidence: 74%

“…Many mediators are responsible for the development and progression of inflammatory response in the intestine. However, one of the major mediators during intestinal inflammation process is inducible nitric oxide synthesis (iNOS) [19][20][21]. Under various conditions, iNOS is considered an important enzyme in the inflammatory response, leading to tissue injury by its multiple actions including apoptosis inducement, oxygen free-radical production, and mitochondrial injury effect [22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Chronic Kidney Disease Elicits an Intestinal Inflammation Resulting in Intestinal Dysmotility Associated with the Activation of Inducible Nitric Oxide Synthesis in Rat

et al. 2018

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This study was conducted to investigate whether chronic kidney disease (CKD) affects intestinal inflammation and intestinal motility and the underlying mechanisms. Rats were randomized into control group and uremic group. Uremia rats were induced by the 5/6 kidney resection, while the control went through the same procedures but without any kidney resection. Intestinal motility was assessed by charcoal transport assay; intestinal inflammation was assessed by analyses of levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 in the ileum tissue. The inducible nitric oxide synthesis (iNOS) activity was assessed in the ileum tissue. The results showed that the intestinal motility in uremic group was significantly decreased compared with that in the control group on postoperative weeks 8 and 10. Meanwhile, the uremic group presented significantly higher concentrations of TNF-α, IL-6, and IL-10 than control group on postoperative weeks 8 and/or 10, and higher gene expression on postoperative weeks 6, 8, and 10. Furthermore, the intestinal iNOS activity in the uremic group was significantly increased compared with that in control group on postoperative weeks 8 and 10. These results suggest that CKD could induce intestinal inflammation and lead to intestinal dysmotility, which may be associated with iNOS activation in the intestine.

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“…21,22 The endotoxemia associated with a high-fat diet could initiate myenteric inducible NOS activation, known to increase in neurons after the systemic administration of LPS, 56 and can induce an overproduction of NO in nitrergic neurons, leading to oxidative stress and apoptosis. 42,57 This will be the focus of our future studies as we continue to understand the mechanisms of a HFDinduced nitrergic enteric neuronal degeneration and delayed colonic transit. One possibility is that the loss of nitrergic myenteric neurons leading to a reduction of the inhibitory tone can contribute to a hypercontractility, abnormal peristalsis, and subsequent constipation.…”

Section: Discussionmentioning

confidence: 99%

26 Intestinal Dysbiosis Contributes to the Delayed Gastrointestinal Transit in High Fat Diet Fed Mice

Anitha¹,

Nezami²,

Mwangi³

et al. 2014

Gastroenterology

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Early inflammatory damage to intestinal neurons occurs via inducible nitric oxide synthase

Cited by 38 publications

References 74 publications

Focal, but not global, cerebral ischaemia causes loss of myenteric neurons and upregulation of vasoactive intestinal peptide in mouse ileum

Focal, but not global, cerebral ischaemia causes loss of myenteric neurons and upregulation of vasoactive intestinal peptide in mouse ileum

Chronic Kidney Disease Elicits an Intestinal Inflammation Resulting in Intestinal Dysmotility Associated with the Activation of Inducible Nitric Oxide Synthesis in Rat

26 Intestinal Dysbiosis Contributes to the Delayed Gastrointestinal Transit in High Fat Diet Fed Mice

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