Vagus nerve stimulation alleviated cerebral ischemia and reperfusion injury in rats by inhibiting pyroptosis via α7 nicotinic acetylcholine receptor

Tang, Hao; Li, Jiani; Zhou, Qinxiang; Li, Sheng; Xie, Chenchen; Niu, Lingchuan; Ma, Jue; Li, Changqing

doi:10.1038/s41420-022-00852-6

Cited by 37 publications

(20 citation statements)

References 54 publications

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“…Importantly, VN stimulation, used in management of treatment-resistant depression, 85 may be neuroprotective after stroke. 86 Both VN-dependent and T cell-dependent cholinergic signaling regulate Paneth cell’s antimicrobial peptide production and epithelial cell proliferation. 87 VN stimulation activates the α7 nicotinic acetylcholine receptor, an important mediator of the cholinergic anti-inflammatory pathway involved in the response to stroke.…”

Section: Neural Pathwaysmentioning

confidence: 99%

Aging Microbiota-Gut-Brain Axis in Stroke Risk and Outcome

Honarpisheh

Bryan

McCullough

2022

Circulation Research

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The microbiota-gut-brain-axis (MGBA) is a bidirectional communication network between gut microbes and their host. Many environmental and host-related factors affect the gut microbiota. Dysbiosis is defined as compositional and functional alterations of the gut microbiota that contribute to the pathogenesis, progression and treatment responses to disease. Dysbiosis occurs when perturbations of microbiota composition and function exceed the ability of microbiota and its host to restore a symbiotic state. Dysbiosis leads to dysfunctional signaling of the MGBA, which regulates the development and the function of the host’s immune, metabolic, and nervous systems. Dysbiosis-induced dysfunction of the MGBA is seen with aging and stroke, and is linked to the development of common stroke risk factors such as obesity, diabetes, and atherosclerosis. Changes in the gut microbiota are also seen in response to stroke, and may impair recovery after injury. This review will begin with an overview of the tools used to study the MGBA with a discussion on limitations and potential experimental confounders. Relevant MGBA components are introduced and summarized for a better understanding of age-related changes in MGBA signaling and its dysfunction after stroke. We will then focus on the relationship between the MGBA and aging, highlighting that all components of the MGBA undergo age-related alterations that can be influenced by or even driven by the gut microbiota. In the final section, the current clinical and preclinical evidence for the role of MGBA signaling in the development of stroke risk factors such as obesity, diabetes, hypertension, and frailty are summarized, as well as microbiota changes with stroke in experimental and clinical populations. We conclude by describing the current understanding of microbiota-based therapies for stroke including the use of pre-/pro-biotics and supplementations with bacterial metabolites. Ongoing progress in this new frontier of biomedical sciences will lead to an improved understanding of the MGBA’s impact on human health and disease.

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Section: Neural Pathwaysmentioning

confidence: 99%

Aging Microbiota-Gut-Brain Axis in Stroke Risk and Outcome

Honarpisheh

Bryan

McCullough

2022

Circulation Research

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“…It establishes a crucial connection between the brain and the gastrointestinal tract and sends information about the state of the inner organs to the brain, which aids in homeostasis of bodily functions. Vagus nerve stimulation is a promising supportive treatment for refractory depression, posttraumatic stress disorder, and inflammatory bowel disease, inhibits cytokine production, and positively effects beneficial monoaminergic brain signaling in psychiatric conditions, such as mood and anxiety [ 61 , 62 , 63 ], and also for the treatment of traumatically injured brain tissues [ 64 , 65 , 66 , 67 , 68 , 69 ]. Gut bacteria have beneficial effects on mood and anxiety through the bioactive factors they produce, which are transported by the vagus nerve to the brain.…”

Section: Therapeutic Vagus Nerve Stimulationmentioning

confidence: 99%

The Potential of Flavonoids and Flavonoid Metabolites in the Treatment of Neurodegenerative Pathology in Disorders of Cognitive Decline

Melrose

2023

Antioxidants

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Flavonoids are a biodiverse family of dietary compounds that have antioxidant, anti-inflammatory, antiviral, and antibacterial cell protective profiles. They have received considerable attention as potential therapeutic agents in biomedicine and have been widely used in traditional complimentary medicine for generations. Such complimentary medical herbal formulations are extremely complex mixtures of many pharmacologically active compounds that provide a therapeutic outcome through a network pharmacological effects of considerable complexity. Methods are emerging to determine the active components used in complimentary medicine and their therapeutic targets and to decipher the complexities of how network pharmacology provides such therapeutic effects. The gut microbiome has important roles to play in the generation of bioactive flavonoid metabolites retaining or exceeding the antioxidative and anti-inflammatory properties of the intact flavonoid and, in some cases, new antitumor and antineurodegenerative bioactivities. Certain food items have been identified with high prebiotic profiles suggesting that neutraceutical supplementation may be beneficially employed to preserve a healthy population of bacterial symbiont species and minimize the establishment of harmful pathogenic organisms. Gut health is an important consideration effecting the overall health and wellbeing of linked organ systems. Bioconversion of dietary flavonoid components in the gut generates therapeutic metabolites that can also be transported by the vagus nerve and systemic circulation to brain cell populations to exert a beneficial effect. This is particularly important in a number of neurological disorders (autism, bipolar disorder, AD, PD) characterized by effects on moods, resulting in depression and anxiety, impaired motor function, and long-term cognitive decline. Native flavonoids have many beneficial properties in the alleviation of inflammation in tissues, however, concerns have been raised that therapeutic levels of flavonoids may not be achieved, thus allowing them to display optimal therapeutic effects. Dietary manipulation and vagal stimulation have both yielded beneficial responses in the treatment of autism spectrum disorders, depression, and anxiety, establishing the vagal nerve as a route of communication in the gut-brain axis with established roles in disease intervention. While a number of native flavonoids are beneficial in the treatment of neurological disorders and are known to penetrate the blood–brain barrier, microbiome-generated flavonoid metabolites (e.g., protocatechuic acid, urolithins, γ-valerolactones), which retain the antioxidant and anti-inflammatory potency of the native flavonoid in addition to bioactive properties that promote mitochondrial health and cerebrovascular microcapillary function, should also be considered as potential biotherapeutic agents. Studies are warranted to experimentally examine the efficacy of flavonoid metabolites directly, as they emerge as novel therapeutic options.

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“…In animal models with cerebral ischemia/reperfusion, VNS had a neuroprotective effect by reducing infarct volume and neurological deficits, partly mediated by its anti-inflammatory properties (13). Our previous findings indeed showed that VNS exerted its neuroprotective effect via the suppression of apoptosis and pyroptosis, as well as through the modulation of neuroinflammation (14,15). Furthermore, VNS was shown to suppress microglia activation and reduce neuroinflammation by regulating the NF-kB pathway (16).…”

Section: Introductionmentioning

confidence: 79%

USP10 is a potential mediator for vagus nerve stimulation to alleviate neuroinflammation in ischaemic stroke by inhibiting NF-κB signalling pathway

et al. 2023

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BackgroundVagus nerve stimulation (VNS) has a protective effect on neurological recovery in ischaemic stroke. However, its underlying mechanism remains to be clarified. Ubiquitin-specific protease 10 (USP10), a member of the ubiquitin-specific protease family, has been shown to inhibit the activation of the NF-κB signalling pathway. Therefore, this study investigated whether USP10 plays a key role in the protective effect of VNS against ischemic stroke and explore its mechanism.MethodsIschaemic stroke model was constructed by transient middle cerebral artery occlusion (tMCAO) in mice. VNS was performed at 30 min, 24hr, and 48hr after the establishment of tMCAO model. USP10 expression induced by VNS after tMCAO was measured. LV-shUSP10 was used to establish the model with low expression of USP10 by stereotaxic injection technique. The effects of VNS with or without USP10 silencing on neurological deficits, cerebral infarct volume, NF-κB pathway activation, glial cell activation, and release of pro-inflammation cytokines were assessed.ResultsVNS enhanced the expression of USP10 following tMCAO. VNS ameliorated neurological deficits and reduced cerebral infarct volume, but this effect was inhibited by silencing of USP10. Activation of the NF-κB pathway and the expression of inflammatory cytokines induced by tMCAO were suppressed by VNS. Moreover, VNS promoted the pro-to-anti-inflammatory response of microglia and inhibited activation of astrocytes, while silencing of USP10 prevented the neuroprotective and anti-neuroinflammatory effects of VNS.ConclusionUSP10 is a potential mediator for VNS to alleviate neurological deficits, neuroinflammation, and glial cell activation in ischaemic stroke by inhibiting NF-κB signalling pathway.

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Vagus nerve stimulation alleviated cerebral ischemia and reperfusion injury in rats by inhibiting pyroptosis via α7 nicotinic acetylcholine receptor

Cited by 37 publications

References 54 publications

Aging Microbiota-Gut-Brain Axis in Stroke Risk and Outcome

Aging Microbiota-Gut-Brain Axis in Stroke Risk and Outcome

The Potential of Flavonoids and Flavonoid Metabolites in the Treatment of Neurodegenerative Pathology in Disorders of Cognitive Decline

USP10 is a potential mediator for vagus nerve stimulation to alleviate neuroinflammation in ischaemic stroke by inhibiting NF-κB signalling pathway

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