Selective Activation of Basal Forebrain Cholinergic Neurons Attenuates Polymicrobial Sepsis–Induced Inflammation via the Cholinergic Anti-Inflammatory Pathway

Zhai, Qian; Lai, Dengming; Cui, Ping; Zhou, Rui; Chen, Qixing; Hou, Jinchao; Su, Yun-Ting; Pan, Libiao; Ye, Hui; Zhao, J. W.; Fang, Xiangming

doi:10.1097/ccm.0000000000002646

Cited by 29 publications

(39 citation statements)

References 34 publications

(36 reference statements)

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“…As a promising preservation technique, it has been shown that pulsed ultrasound (US) can protect kidneys from IRI [15], perhaps by invoking an anti-inflammatory response. This is consistent with the regulatory effects of an inflammatory reflex called the cholinergic antiinflammatory pathway (CAP) [16,17]. In this reflex, inflammatory regulatory signals are transmitted by the peripheral and central nervous systems.…”

Section: Introductionsupporting

confidence: 71%

“…Therefore, reducing inflammation is crucial. Recent studies have found that CAP is a new inflammatory regulatory mechanism [16,17]. CAP can conduct an anti-inflammatory signal and travel through the efferent fibers of the vagus nerve; these signals reach the organs which have the reticular endothelial system, such as the spleen, liver, and heart, and then release acetylcholine (Ach), binding with macrophages and other immune cells on the expression of alpha 7 nicotine-type acetylcholine receptor (α7nAChR) to inhibit proinflammatory cytokines from releasing, thus acting as anti-inflammatory and analgesic agents [18].…”

Section: Discussionmentioning

confidence: 99%

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Vagus Nerve Stimulation Alleviates Hepatic Ischemia and Reperfusion Injury by Regulating Glutathione Production and Transformation

Xia

Liu

Liang

et al. 2020

Oxidative Medicine and Cellular Longevity

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Inflammation and oxidative stress are pivotal mechanisms for the pathogenesis of ischemia and reperfusion injury (IRI). Vagus nerve stimulation (VNS) may participate in maintaining oxidative homeostasis and response to external stimulus or injury. We investigated whether the in vivo VNS can protect the liver from IRI. In this study, hepatic IRI were induced by ligating the vessels supplying the left and middle lobes of the liver, which underwent 1 h occlusion followed with 24 h reperfusion. VNS was initiated 15 min after ischemia and continued 30 min. Hepatic function, histology, and apoptosis rates were evaluated after 24 h reperfusion. Compared with the IRI group, VNS significantly improved hepatic function. The protective effect was accompanied by a reduction in histological damage in the ischemic area, and the apoptosis rate of hepatocytes has considerable reduction. To find the underlying mechanism, proteomic analysis was performed and differential expression of glutathione synthetase (GSS) and glutathione S-transferase (GST) was observed. Subsequently, test results indicated that VNS upregulated the expression of mRNA and protein of GSS and GST. Meanwhile, VNS increased the plasma levels of glutathione and glutathione peroxidases. We found that VNS alleviated hepatic IRI by upregulating the antioxidant glutathione via the GSS/glutathione/GST signaling pathway.

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Section: Introductionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Vagus Nerve Stimulation Alleviates Hepatic Ischemia and Reperfusion Injury by Regulating Glutathione Production and Transformation

Xia

Liu

Liang

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…A close relationship has been noted between poor outcomes and indicators of CAP malfunction, such as a decrease in heart rate variability, an increase in cholinesterase activity, and downregulation of α7nAchR mRNA expression in peripheral immune cells [113][114][115]. Manipulation of CAP activity through stimulating brain cholinergic nuclei or vagus nerve, inhibiting cholinesterase activity and administering agonists of α7nAchR, is beneficial for organ function and survival of septic animals by reconstruction or simulation of CAP effects [9,10,116,117]. In addition, the CAP is recognized as a neuroprotective mechanism that is capable of reducing both systemic and cerebral inflammation, which further attenuates brain damage after activation [118,119].…”

Section: Cholinergic Anti-inflammatory Pathwaymentioning

confidence: 98%

Sepsis-associated encephalopathy: a vicious cycle of immunosuppression

Ren

Yao

Zhang

et al. 2020

J Neuroinflammation

156

131

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Sepsis-associated encephalopathy (SAE) is commonly complicated by septic conditions, and is responsible for increased mortality and poor outcomes in septic patients. Uncontrolled neuroinflammation and ischemic injury are major contributors to brain dysfunction, which arises from intractable immune malfunction and the collapse of neuroendocrine immune networks, such as the cholinergic anti-inflammatory pathway, hypothalamic-pituitaryadrenal axis, and sympathetic nervous system. Dysfunction in these neuromodulatory mechanisms compromised by SAE jeopardizes systemic immune responses, including those of neutrophils, macrophages/monocytes, dendritic cells, and T lymphocytes, which ultimately results in a vicious cycle between brain injury and a progressively aberrant immune response. Deep insight into the crosstalk between SAE and peripheral immunity is of great importance in extending the knowledge of the pathogenesis and development of sepsis-induced immunosuppression, as well as in exploring its effective remedies.

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“…Both afferent and efferent fibers of the vagus nerve have been shown to communicate with limbic structures, where afferents increase cholinergic signaling in the BF (Broncel et al, 2018;Suarez et al, 2018). This BF cholinergic signaling reduces pro-inflammatory cytokines both centrally and peripherally in an effect which requires an intact vagus nerve (Zhai et al, 2017). Vagal afferents may also influence cholinergic signaling through norepinephrine production from the locus coeruleus (LC), which in turn promotes ACh production from the Nucleus Basalis of Meynert (Kaczmarczyk et al, 2018).…”

Section: The Anti-inflammatory Role Of the Cholinergic Systemmentioning

confidence: 99%

Cholinergic Modulation of Glial Function During Aging and Chronic Neuroinflammation

Gamage

Wagnon

Rossetti

et al. 2020

Front. Cell. Neurosci.

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Aging is a complex biological process that increases the risk of age-related cognitive degenerative diseases such as dementia, including Alzheimer's disease (AD), Lewy Body Dementia (LBD), and mild cognitive impairment (MCI). Even non-pathological aging of the brain can involve chronic oxidative and inflammatory stress, which disrupts the communication and balance between the brain and the immune system. There has been an increasingly strong connection found between chronic neuroinflammation and impaired memory, especially in AD. While microglia and astrocytes, the resident immune cells of the central nervous system (CNS), exerting beneficial effects during the acute inflammatory phase, during chronic neuroinflammation they can become more detrimental. Central cholinergic circuits are involved in maintaining normal cognitive function and regulating signaling within the entire cerebral cortex. While neuronal-glial cholinergic signaling is anti-inflammatory and anti-oxidative, central cholinergic neuronal degeneration is implicated in impaired learning, memory sleep regulation, and attention. Although there is evidence of cholinergic involvement in memory, fewer studies have linked the cholinergic anti-inflammatory and anti-oxidant pathways to memory processes during development, normal aging, and disease states. This review will summarize the current knowledge of cholinergic effects on microglia and astroglia, and their role in both anti-inflammatory and anti-oxidant mechanisms, concerning normal aging and chronic neuroinflammation.

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Selective Activation of Basal Forebrain Cholinergic Neurons Attenuates Polymicrobial Sepsis–Induced Inflammation via the Cholinergic Anti-Inflammatory Pathway

Abstract: Supplemental Digital Content is available in the text.

Cited by 29 publications

References 34 publications

Vagus Nerve Stimulation Alleviates Hepatic Ischemia and Reperfusion Injury by Regulating Glutathione Production and Transformation

Vagus Nerve Stimulation Alleviates Hepatic Ischemia and Reperfusion Injury by Regulating Glutathione Production and Transformation

Sepsis-associated encephalopathy: a vicious cycle of immunosuppression

Cholinergic Modulation of Glial Function During Aging and Chronic Neuroinflammation

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