PPARγ Upregulation Induced by Vagus Nerve Stimulation Exerts Anti-Inflammatory Effect in Cerebral Ischemia/Reperfusion Rats

Jiang, Ying; Li, Longling; Liu, Bin; Zhang, Yanhong; Chen, Qian; Li, Changqing

doi:10.12659/msm.891407

Cited by 41 publications

(27 citation statements)

References 30 publications

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“…Indeed, recent studies show that invasive cVNS decreases TNF-α, IL-1β, IL-6, and increases expression of α7nAChRs on microglia following MCAO and peroxisome proliferator-activated receptor gamma and microRNA210 may play a mechanistic role in cVNS-induced neuroprotection. [8, 32, 33] We did not observe a significant reduction in IL-1β and IL-6 levels with transcutaneous stimulation. This could be due to differences in animal strains (Sprague-Dawley vs. SHR) as well as the method used to detect interleukins (ELISA vs. immunohistochemistry).…”

Section: Discussioncontrasting

confidence: 53%

Transcutaneous Cervical Vagus Nerve Stimulation Ameliorates Acute Ischemic Injury in Rats

Nasser

Simon³

et al. 2016

Brain Stimulation

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Background Direct stimulation of the vagus nerve in the neck via surgically implanted electrodes is protective in animal models of stroke. We sought to determine the safety and efficacy of a non-invasive cervical VNS (nVNS) method using surface electrodes applied to the skin overlying the vagus nerve in the neck in a model of middle cerebral artery occlusion (MCAO). Methods nVNS was initiated variable times after MCAO hour in rats (n=33). Control animals received sham stimulation (n=33). Infarct volume and functional outcome were assessed on day 7. Brains were processed by immunohistochemistry for microglial activation and cytokine levels. The ability of nVNS to activate the nucleus tractus solitarius (NTS) was assessed using c-Fos immunohistochemistry. Results Infarct volume was 43.15±3.36 percent of the contralateral hemisphere (PCH) in control and 28.75±4.22 PCH in nVNS-treated animals (p<0.05). The effect of nVNS on infarct size was consistent when stimulation was initiated up to 4 hours after MCAO. There was no difference in heart rate and blood pressure between control and nVNS-treated animals. The number of c-Fos positive cells was 32.4±10.6 and 6.2±6.3 in the ipsilateral NTS (p<0.05) and 30.4±11.2 and 5.8±4.3 in the contralateral NTS (p<0.05) in nVNS-treated and control animals, respectively. nVNS reduced the number of Iba-1, CD68, and TNF-α positive cells and increased the number of HMGB1 positive cells. Conclusions nVNS inhibits ischemia-induced immune activation and reduces the extent of tissue injury and functional deficit in rats without causing cardiac or hemodynamic adverse effects when initiated up to 4 hours after MCAO.

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Section: Discussioncontrasting

confidence: 53%

Transcutaneous Cervical Vagus Nerve Stimulation Ameliorates Acute Ischemic Injury in Rats

Nasser

Simon³

et al. 2016

Brain Stimulation

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“…However, our results showed that VNS increased locomotion in lesioned rats, providing the first look at the effects of VNS on the SN-DA system and locomotion. Previous studies using similar stimulation paradigms have focused on a wide variety of behavioral components related to other diseases [13,14,39,40]. Longitudinal locomotor data shows that in lesion non-VNS rats, locomotion continues to decline over the course of the study.…”

Section: Discussionmentioning

confidence: 99%

“…While acute microglial activation may result in neuroprotective secretions from microglia, prolonged activation results in pro-inflammatory secretions that are thought to contribute to neurodegeneration in chronic diseases such as PD [9,61,62]. VNS in a rat model of cerebral ischemia reduced inflammation via reduced glial activation and increased release of anti-inflammatory molecules, having a protective effect on neuronal populations and improving behavior [14,63,64]. Thus, the reduced inflammation after VNS in lesioned rats may contribute to the neuronal and behavioral improvements observed in this study.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, here we study the effects of vagus nerve stimulation (VNS) on motor function, LC-NE and SN-DA systems, α-synuclein, and neuroinflammation in a rat model of PD. Rodent models of cerebral ischemia and depression show that VNS has beneficial effects on LC neurons, decreases both inflammation and oxidative stress, and increases neurotrophic factors [12,13,14]. Because dysfunction in these mechanisms is known to contribute to degeneration in PD, a multi-modal approach like VNS may be beneficial in PD patients, where pharmaceutical trials targeting one mechanism at a time have failed, including a meta-analysis examining the impact of NSAIDs on the risk of developing PD [15].…”

Section: Introductionmentioning

confidence: 99%

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Vagus nerve stimulation improves locomotion and neuronal populations in a model of Parkinson's disease

et al. 2017

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Background Parkinson’s disease (PD) is a progressive, neurodegenerative disorder with no disease-modifying therapies, and symptomatic treatments are often limited by debilitating side effects. In PD, locus coeruleus noradrenergic (LC-NE) neurons degenerate prior to substantia nigra dopaminergic (SN-DA) neurons. Vagus nerve stimulation (VNS) activates LC neurons, and decreases pro-inflammatory markers, allowing improvement of LC targets, making it a potential PD therapeutic. Objective To assess therapeutic potential of VNS in a PD model. Methods To mimic the progression of PD degeneration, rats received a systemic injection of noradrenergic neurotoxin DSP-4, followed one week later by bilateral intrastriatal injection of dopaminergic neurotoxin 6-hydroxydopamine. At this time, a subset of rats also had vagus cuffs implanted. After eleven days, rats received a precise VNS regimen twice a day for ten days, and locomotion was measured during each afternoon session. Immediately following final stimulation, rats were euthanized, and left dorsal striatum, bilateral SN and LC were sectioned for immunohistochemical detection of monoaminergic neurons (tyrosine hydroxylase, TH), α-synuclein, astrocytes (GFAP) and microglia (Iba-1). Results VNS significantly increased locomotion of lesioned rats. VNS also resulted in increased expression of TH in striatum, SN, and LC; decreased SN α-synuclein expression; and decreased expression of glial markers in the SN and LC of lesioned rats. Additionally, saline-treated rats after VNS, had higher LC TH and lower SN Iba-1. Conclusions Our findings of increased locomotion, beneficial effects on LC-NE and SN-DA neurons, decreased α-synuclein density in SN TH-positive neurons, and neuroinflammation suggest VNS has potential as a novel PD therapeutic.

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“…PPAR beta/delta can reduce oxidative stress and exerts anti-inflammatory effects through regulating the interaction between neutrophils and endothelial cells in the acute inflammatory response. PPAR gamma is involved in acute or chronic injury and inflammation of the central nervous system, and has a protective effect on the proliferation and differentiation in fat or glucolipid metabolism, cerebral ischemia and reperfusion injury, and immune systems [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Changes in Plasma PPARs Levels in Migraine Patients

Zhang

et al. 2015

Med Sci Monit

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BackgroundThe aim of this study was to observe the change in plasma PPARs (peroxisome proliferator-activated receptors) level during various periods and in different subtypes in migraine patients.Material/MethodsWe divided 227 patients with migraine into 2 main groups: the attack period group (n=98) and the attack-free period group (n=129). Patients were further divided into 4 subgroups according to whether they had aura symptoms. The control group consisted of 100 healthy subjects. We collected the clinical data of patients and measured the plasma levels of PPARs using enzyme-linked immunoassay (ELISA). We used SPSS software for statistical analysis.ResultsWe found no significant difference in age, BMI, blood pressure, or blood lipid level among migraine patients during the headache attack period and during the headache-free period compared with the control group. The PPARα and PPARβ/δ levels during the headache attack period were significantly higher than during the headache free period and in healthy controls. The PPARγ levels during the headache attack period were significantly lower than those during the headache-free period and in the healthy control group. The PPARs levels during the headache attack period were significantly different from those during the headache-free period, regardless of presence or absence of aura. The PPARs levels during the headache-free period were not significantly different from those of the healthy control group. The level of PPARs has no significant differences between migraine with aura group and without aura group, regardless of whether headache attack.ConclusionsPPARs involved in the pathogenesis of migraine. Presence of absence of aura had no obvious effect on PPARs level.

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PPARγ Upregulation Induced by Vagus Nerve Stimulation Exerts Anti-Inflammatory Effect in Cerebral Ischemia/Reperfusion Rats

Cited by 41 publications

References 30 publications

Transcutaneous Cervical Vagus Nerve Stimulation Ameliorates Acute Ischemic Injury in Rats

Transcutaneous Cervical Vagus Nerve Stimulation Ameliorates Acute Ischemic Injury in Rats

Vagus nerve stimulation improves locomotion and neuronal populations in a model of Parkinson's disease

Changes in Plasma PPARs Levels in Migraine Patients

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