Brain tumour necrosis factor-  modulates neurotransmitters in hypothalamic paraventricular nucleus in heart failure

Kang, Yu‐Ming; He, Rongli; Yang, Limin; Qin, Danian; Guggilam, Anuradha; Elks, Carrie M.; Ning, Yan; Guo, Zheng; Francis, Joseph

doi:10.1093/cvr/cvp160

Cited by 107 publications

(127 citation statements)

References 35 publications

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“…Rats underwent sterile surgery under anesthesia (ketamine + xylazine, ip) for induction of HF by ligation of the left anterior descending coronary artery, or the same surgery without vessel ligation (SHAM), as previously described (Kang et al 2006(Kang et al , 2008a(Kang et al , 2008b(Kang et al , 2009aGuggilam et al 2008).…”

Section: Coronary Ligationmentioning

confidence: 99%

“…Minipumps were connected to the bilateral PVN cannulae for continuous infusion of PTX, which inhibits the production of TNF-α , at a total dose of 10 or 30 μ g/h; ETN, which binds with circulating TNF-α and prevents it from binding to its receptor, at a total dose of 2.5 or 7.5 μ g/h; or aCSF over a 4-week period. The doses used in this study were determined from preliminary studies based on a previous report from our laboratory (Kang et al 2009a). The locations of the microinjection sites in the PVN areas are shown in Fig.…”

Section: Drug Infusionmentioning

confidence: 99%

“…Palkovits's microdissection procedure was used to isolate the PVN, as previously described (MohanKumar et al 1998;Kang et al 2009a). The tissues were collected from both sides of the PVN of individual rat used.…”

Section: Tissue Microdissectionmentioning

confidence: 99%

“…Recent studies also suggest that proinflammatory cytokines and the renin-angiotensin system (RAS) can contribute to these changes (Kang et al 2008a(Kang et al , 2008b(Kang et al , 2009a(Kang et al , 2009b. Our laboratory and others have reported that cytokine blockade in the brain decreases components of the RAS (Kang et al 2008b, Guggilam et al 2008 and that RAS blockade attenuates production of proinflammatory cytokines (Kang et al 2008a(Kang et al , 2009b.…”

mentioning

confidence: 98%

“…We inhibited cytokine synthesis in the brain with centrally infused pentoxifylline (PTX) and found that lowering hypothalamic levels of TNF-α and IL-1β without changing plasma cytokine levels is associated with reductions in brain renin, ACE, and AT1-R, strongly suggests that proinflammatory cytokines are intrinsically involved in regulating brain RAS, and thus sympathetic nerve activity and extracellular fluid volume, in rats with HF. Animals were intracerebroventricularly (ICV) treated with the angiotensin type 1 receptor (AT1-R) antagonist losartan and we found that plasma levels of NE, angiotensin II and proinflammatory cytokines were reduced (Guggilam et al 2008;Kang et al 2008aKang et al , 2008bKang et al , 2009a. However, it is unknown whether proinflammatory cytokines in the PVN alter angiotensin type 1 receptor (AT1-R) within the PVN to modulate neurotransmitters and contribute to sympathoexcitation in HF.…”

mentioning

confidence: 99%

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TNF-.ALPHA. in Hypothalamic Paraventricular Nucleus Contributes to Sympathoexcitation in Heart Failure by Modulating AT1 Receptor and Neurotransmitters

Kang

Wang

Yang

et al. 2010

Tohoku J. Exp. Med.

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Proinflammatory cytokines, including tumor necrosis factor (TNF)-α , augment the progression of heart failure (HF) that is characterized by sympathoexcitation. In this study, we explored the role of TNF-α in hypothalamic paraventricular nucleus (PVN) in the exaggerated sympathetic activity observed in HF. Heart failure rats were made by ligating the left anterior descending coronary artery. The expression levels of angiotensin type 1 receptor (AT1-R) and neurotransmitters were analyzed in the PVN of HF rats that received direct PVN infusion of a TNF-α blocker (pentoxifylline or etanercept) or vehicle. Sham-operated control (SHAM) or HF rats were treated for 4 weeks through PVN infusion with each TNF-α blocker or vehicle. Rats with HF had higher levels of glutamate, norepinephrine, AT1-R and tyrosine hydroxylase (TH), and lower levels of gamma-aminobutyric acid (GABA), neuronal nitric oxide synthase (nNOS) and the 67-kDa isoform of glutamate decarboxylase (GAD67) in the PVN when compared to SHAM rats. Plasma levels of cytokines, norepinephrine and angiotensin II and renal sympathetic nerve activity (RSNA) were increased in HF rats. PVN infusion of pentoxifylline or etanercept attenuated the decreases in PVN GABA, nNOS and GAD67, and the increases in RSNA and PVN glutamate, norepinephrine, TH and AT1-R observed in HF rats. We have developed a novel method for chronic and continuous infusion of drugs directly into the PVN and provided evidence that TNF-α in the PVN modulates neurotransmitters and the expression of AT1 receptor, which could account for exaggerated sympathetic activity in HF.

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Section: Coronary Ligationmentioning

confidence: 99%

Section: Drug Infusionmentioning

confidence: 99%

Section: Tissue Microdissectionmentioning

confidence: 99%

mentioning

confidence: 98%

mentioning

confidence: 99%

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TNF-.ALPHA. in Hypothalamic Paraventricular Nucleus Contributes to Sympathoexcitation in Heart Failure by Modulating AT1 Receptor and Neurotransmitters

Kang

Wang

Yang

et al. 2010

Tohoku J. Exp. Med.

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AIEgen‐Based Covalent Organic Frameworks for Preventing Malignant Ventricular Arrhythmias Via Local Hyperthermia Therapy

Zhang

Guo

et al. 2023

Advanced Materials

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We report the engineering of aggregation‐induced emission luminogens (AIEgen) based covalent organic frameworks (COFs), TDTA‐COF, BTDTA‐COF, and BTDBETA‐COF, as hyperthermia agents for inhibiting the occurrence of malignant ventricular arrhythmias (VAs). These AIE COFs exhibit dual functionality, as they not only directly modulate the function and neural activity of stellate ganglion (SG) through local hyperthermia therapy (LHT) but also induce the browning of white fat and improve the neuro‐inflammation peri‐SG microenvironment, which is favorable for inhibiting ischemia‐induced VAs. In vivo studies have confirmed that BTDBETA‐COF‐mediated LHT enhances thermogenesis and browning‐related gene expression, thereby serving a synergistic role in combating VAs. Transcriptome analysis of peri‐SG adipose tissue reveals a substantial downregulation of inflammatory cytokines, highlighting the potency of BTDBETA‐COF‐mediated LHT in ameliorating the neuro‐inflammation peri‐SG microenvironment and offering myocardial and arrhythmia protection. Our work on AIE COF‐based hyperthermia agent for VAs inhibition providing a new avenue for mitigating cardiac sympathetic nerve hyperactivity.AIEgen; covalent organic frameworks; hyperthermia agent; malignant ventricular arrhythmias; neuromodulationThis article is protected by copyright. All rights reserved

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Roles for γ‐aminobutyric acid in the development of the paraventricular nucleus of the hypothalamus

McClellan

Stratton

Tobet

2010

J of Comparative Neurology

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The development of the hypothalamic paraventricular nucleus (PVN) involves several factors that work together to establish a cell group that regulates neuroendocrine functions and behaviors. A number of molecular markers were noted within the developing PVN, including estrogen receptors (ER), neuronal nitric oxide synthase (nNOS) and brain derived neurotrophic factor (BDNF). By contrast, immunoreactive gamma-aminobutyric acid (GABA) was found in cells and fibers surrounding the PVN. Two animal models were used to test the hypothesis that GABA works through GABAA and GABAB receptors to influence the development of the PVN. Treatment with bicuculline to decrease GABAA receptor signaling from embryonic day (E)10 to 17 resulted in fewer cells containing immunoreactive (ir)-ERα in the region of the PVN versus control. GABABR1 receptor subunit knockout mice were used to examine the PVN at P0 without GABAB signaling. In female but not male GABABR1 subunit knockout mice, the positions of cells containing ir-ERα shifted from medial to lateral compared to wildtype controls, while the total number of ir-ERα containing cells was unchanged. In E17 knockout mice, ir-nNOS cells and fibers were spread over a greater area. There was also a significant decrease in ir-BDNF in the knockout mice in a region dependent manner. Changes in cell position and protein expression subsequent to disruption of GABA signaling may be due, in part, to changes in nNOS and BDNF signaling. Based on the current study, the PVN can be added as another site where GABA exerts morphogenetic actions in development.

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Brain tumour necrosis factor- modulates neurotransmitters in hypothalamic paraventricular nucleus in heart failure

Abstract: This study, for the first time, demonstrates that proinflammatory cytokines modulate neurotransmitters in the PVN and contribute to sympathoexcitation in HF.

Cited by 107 publications

References 35 publications

TNF-.ALPHA. in Hypothalamic Paraventricular Nucleus Contributes to Sympathoexcitation in Heart Failure by Modulating AT1 Receptor and Neurotransmitters

TNF-.ALPHA. in Hypothalamic Paraventricular Nucleus Contributes to Sympathoexcitation in Heart Failure by Modulating AT1 Receptor and Neurotransmitters

AIEgen‐Based Covalent Organic Frameworks for Preventing Malignant Ventricular Arrhythmias Via Local Hyperthermia Therapy

Roles for γ‐aminobutyric acid in the development of the paraventricular nucleus of the hypothalamus

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