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Intermedin in Paraventricular Nucleus Attenuates Sympathoexcitation and Decreases TLR4-Mediated Sympathetic Activation via Adrenomedullin Receptors in Rats with Obesity-Related Hypertension

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Neuroscience Bulletin 2019年第1期35卷 34-46页

作者： Jing Sun Xing-Sheng Ren Ying Kang Hang-Bing Dai Lei Ding Ning Tong Guo-Qing Zhu Ye-Bo Zhou Key Laboratory of Cardiovascular Disease and Molecular Intervention Department of PhysiologyNanjing Medical UniversityNanjing 211166China Department of Pathophysiology Xuzhou Medical CollegeXuzhou 221004China Department of Neurology Heze Municipal HospitalHeze 274000China

Intermedin/adrenomedullin-2(IMD/AM2), a member of the calcitonin gene-related peptide/AM family,plays an important role in protecting the cardiovascular system. However, its role in the enhanced sympathoexcitation in obesity-related hypertension is unknown. In this study, we investigated the effects of IMD in the Paraventricular nucleus(PVN) of the hypothalamus on sympathetic nerve activity(SNA), and lipopolysaccharide(LPS)-induced sympathetic activation in obesity-related hypertensive(OH)rats induced by a high-fat diet for 12 weeks. Acute experiments were performed under anesthesia. The dynamic alterations of sympathetic outflow were evaluated as changes in renal SNA and mean arterial pressure(MAP) in response to specific drugs. Male rats were fed a control diet(12% kcal as fat) or a high-fat diet(42% kcal as fat) for 12 weeks to induce OH. The results showed that IMD protein in the PVN was downregulated, but Toll-like receptor 4(TLR4) and plasma norepinephrine(NE, indicating sympathetic hyperactivity) levels, and systolic blood pressure were increased in OH rats. LPS(0.5 lg/50 nL)-induced enhancement of renal SNA and MAP was greater in OH rats than in obese or control rats. Bilateral PVN microinjection of IMD(50 pmol)caused greater decreases in renal SNA and MAP in OH rats than in control rats, and inhibited LPS-induced sympatheticactivation, and these were effectively prevented in OH rats by pretreatment with the AM receptor antagonist AM22-52.The mitogen-activated protein kinase/extracellular signalregulated kinase(ERK) inhibitor U0126 in the PVN partially reversed the LPS-induced enhancement of SNA. However,IMD in the PVN decreased the LPS-induced ERK activation,which was also effectively prevented by AM22-52. Chronic IMD administration resulted in significant reductions in the plasma NE level and blood pressure in OH rats. Moreover,IMD lowered the TLR4 protein expression and ERK activation in the PVN, and decreased the LPS-induced sympathetic overactivity. These results indicate that IMD in the PVN attenuat

关键词： Intermedin Sympathoexcitation Obesityrelated hypertension Paraventricular nucleus Toll-like receptor 4

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Paraventricular Thalamus as A Major Thalamic Structure for Wake Control

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Neuroscience Bulletin 2019年第5期35卷 946-948页

作者： Yu-Feng Shao Jian-Sheng Lin Yi-Ping Hou Departments of Neuroscience Anatomy Histology and Embryology Key Laboratory of Preclinical Study for New Drugs of Gansu Province School of Basic Medical Sciences Lanzhou University Lanzhou 730000 China Integrative Physiology of the Brain Arousal Systems Lyon Neuroscience Research Center Lyon 69373 France

The thalamus is the gate of the cerebral cortex, the ultimate target for the neural networks controlling behavioral states and cognitive functions. According to the reticular theory initially proposed by Moruzzi and Magoun, excitatory inputs from large reticular zones of the brainstem via widespread intra- and extra-thalamocortical systems finally activate the cerebral cortex to cause generalized cortical activation and wakefulness [1]. This theory proposes a central relay role to the thalamus for cortical activation as supported by early studies using neurodegeneration techniques and by the elegant work of Steriade’s group and other investigators illustrating the electrophysiological mechanisms of the thalamocortical system at the cellular level during wakefulness, rapid eye-movement sleep (REMs) and non-REM sleep (NREMs)[2].

关键词： Paraventricular Thalamus Thalamic Structure Wake Control

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Chronic Intracerebroventricular Infusion of Metformin Inhibits Salt-Sensitive Hypertension via Attenuation of Oxidative Stress and Neurohormonal Excitation in Rat Paraventricular Nucleus

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Neuroscience Bulletin 2019年第1期35卷 57-66页

作者： Xiao-Jing Yu Ya-Nan Zhao Yi-Kang Hou Hong-Bao Li Wen-Jie Xia Hong-Li Gao Kai-Li Liu Qing Su Hui-Yu Yang Bin Liang Wen-Sheng Chen Wei Cui Ying Li Guo-Qing Zhu Zhi-Ming Yang Yu-Ming Kang Department of Physiology and Pathophysiology Xi’an Jiaotong University School of Basic Medical SciencesMinistry of Education Key Laboratory of Environment and Genes Related to DiseasesXi’an Jiaotong UniversityXi’an 710061China Department of Cardiology Second Affiliated Hospital of Shanxi Medical UniversityTaiyuan 030001China Department of Respiratory Medicine Affiliated Jiangyin Hospital of Southeast University Medical SchoolJiangyin 214400China Department of Cardiovascular Surgery Xijing HospitalFourth Military Medical UniversityXi’an 710032China Department of Endocrinology and Metabolism First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an Jiaotong University Health Science CenterXi’an 710061China Department of Plastic and Cosmetic Surgery Gansu Provincial HospitalLanzhou 730000China Key Laboratory of Cardiovascular Disease and Molecular Intervention Department of PhysiologyNanjing Medical UniversityNanjing 210029China

Metformin(MET), an antidiabetic agent, also has antioxidative effects in metabolic-related hypertension.This study was designed to determine whether MET has anti-hypertensive effects in salt-sensitive hypertensive rats by inhibiting oxidative stress in the hypothalamic Paraventricular nucleus(PVN). Salt-sensitive rats received a highsalt(HS) diet to induce hypertension, or a normal-salt(NS)diet as control. At the same time, they received intracerebroventricular(ICV) infusion of MET or vehicle for 6 weeks. We found that HS rats had higher oxidative stress levels and mean arterial pressure(MAP) than NS rats. ICV infusion of MET attenuated MAP and reduced plasma norepinephrine levels in HS rats. It also decreased reactive oxygen species and the expression of subunits of NAD(P)H oxidase, improved the superoxide dismutase activity,reduced components of the renin-angiotensin system, and altered neurotransmitters in the PVN. Our findings suggest that central MET administration lowers MAP in saltsensitive hypertension via attenuating oxidative stress,inhibiting the renin-angiotensin system, and restoring the balance between excitatory and inhibitory neurotransmitters in the PVN.

关键词： Hypertension Paraventricular nucleus Sympathoexcitation Metformin Oxidative stress

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Blockade of c-Src Within the Paraventricular Nucleus Attenuates Inflammatory Cytokines and Oxidative Stress in the Mechanism of the TLR4 Signal Pathway in Salt-Induced Hypertension

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Neuroscience Bulletin 2020年第4期36卷 385-395页

作者： Qing Yang Xiao-Jing Yu Qing Su Qiu-Yue Yi Xin-Ai Song Xiao-Lian Shi Hong-Bao Li Jie Qi Guo-Qing Zhu Yu-Ming Kang Department of Physiology and Pathophysiology Xi'an Jiaotong University School of Basic Medical SciencesKey Laboratory of Environment and Genes Related to Diseases of the Ministry of EducationXi'an Jiaotong UniversityXi’an 710061China Department of Cardiovascular Surgery First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061China Department of Pharmacology School of Basic Medical SciencesXi’an Jiaotong University Health Science CenterXi’an 710061China Key Laboratory of Cardiovascular Disease and Molecular Intervention Department of PhysiologyNanjing Medical UniversityNanjing 210029China

Toll-like receptor 4 (TLR4) and cellular Src (cSrc) are closely associated with inflammatory cytokines and oxidative stress in hypertension, so we designed this study to explore the exact role of c-Src in the mechanism of action of the TLR4 signaling pathway in salt-induced hypertension. Salt-sensitive rats were given a high salt diet for 10 weeks to induce hypertension. This resulted in higher levels of TLR4, activated c-Src, pro-inflammatory cytokines, oxidative stress, and arterial pressure. Infusion of a TLR4 blocker into the hypothalamic Paraventricular nucleus (PVN) decreased the activated c-Src, while microinjection of a c-Src inhibitor attenuated the PVN levels of nuclear factor-kappa B, pro-inflammatory cytokines, and oxidative stress. Our findings suggest that a longterm high-salt diet increases TLR4 expression in the PVN and this promotes the activation of c-Src, which upregulates the expression of pro-inflammatory cytokines and results in the overproduction of reactive oxygen species.Therefore, inhibiting central c-Src activity may be a new target for treating hypertension.

关键词： Toll-like receptor 4 Cellular Src Inflammatory cytokines Oxidative stress Hypothalamic Paraventricular nucleus Salt-induced hypertension

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Blockade of Endogenous Angiotensin-(1–7) in Hypothalamic Paraventricular Nucleus Attenuates High Salt-Induced Sympathoexcitation and Hypertension

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Neuroscience Bulletin 2019年第1期35卷 47-56页

作者： Xiao-Jing Yu Yu-Wang Miao Hong-Bao Li Qing Su Kai-Li Liu Li-Yan Fu Yi-Kang Hou Xiao-Lian Shi Ying Li Jian-Jun Mu Wen-Sheng Chen Wei Cui Guo-Qing Zhu Philip J.Ebenezer Joseph Francis Yu-Ming Kang Department of Physiology and Pathophysiology Xi’an Jiaotong University School of Basic Medical SciencesKey Laboratory of Environment and Genes Related to DiseasesMinistry of EducationXi’an 710061China Comparative Biomedical Sciences School of Veterinary MedicineLouisiana State UniversityBaton RougeLA 70803USA Genetic Engineering Laboratory College of BiotechnologyXi’an UniversityXi’an 710065China Department of Plastic and Cosmetic Surgery Gansu Provincial HospitalLanzhou 730000China Department of Pharmacology School of Basic Medical SciencesXi’an Jiaotong University Health Science CenterXi’an 710061China Department of Cardiovascular Medicine First Affiliated Hospital of the Medical College of Xi’an Jiaotong UniversityXi’an 710061China Department of Cardiovascular Surgery Xijing HospitalFourth Military Medical UniversityXi’an 710032China Department of Endocrinology and Metabolism The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an Jiaotong University Health Science CenterXi’an 710061China Key Laboratory of Cardiovascular Disease and Molecular Intervention Department of PhysiologyNanjing Medical UniversityNanjing 210029China

Angiotensin(Ang)-(1–7) is an important biologically-active peptide of the renin-angiotensin system. This study was designed to determine whether inhibition of Ang-(1–7) in the hypothalamic Paraventricular nucleus(PVN) attenuates sympathetic activity and elevates blood pressure by modulating pro-inflammatory cytokines(PICs)and oxidative stress in the PVN in salt-induced hypertension. Rats were fed either a high-salt(8% NaCl) or a normal salt diet(0.3% NaCl) for 10 weeks, followed by bilateral microinjections of the Ang-(1–7) antagonist A-779 or vehicle into the PVN. We found that the mean arterial pressure(MAP), renal sympathetic nerve activity(RSNA), and plasma norepinephrine(NE) were significantly increased in salt-induced hypertensive rats. The high-salt diet also resulted in higher levels of the PICs interleukin-6, interleukin-1 beta, tumor necrosis factor alpha, and monocyte chemotactic protein-1, as well as higher gp91 phoxexpression and superoxide production in the PVN. Microinjection of A-779(3 nmol/50 nL) into the bilateral PVN of hypertensive rats not only attenuated MAP, RSNA, and NE, but also decreased the PICs and oxidative stress in the PVN. These results suggest that the increased MAP and sympathetic activity in salt-induced hypertension can be suppressed by blockade of endogenous Ang-(1–7) in the PVN, through modulation of PICs and oxidative stress.

关键词： High-salt diet Hypertension Angiotensin(1–7) Paraventricular nucleus Pro-inflammatory cytokines

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Role of the Paraventricular nucleus of the hypothalamus in sleep-wake regulation

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Brain Science Advances 2022年第3期8卷 197-209页

作者： Shan Jiang Lu Chen Zhi-Li Huang Chang-Rui Chen Department of Pharmacology School of Basic Medical SciencesState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceInstitutes of Brain ScienceShanghai Medical College Fudan University

The Paraventricular nucleus of the hypothalamus(PVH)acts as a cohesive functional unit that regulates neuroendocrine and autonomic function,complex behavior,and negative emotions after stress.However,how the PVH integrates arousal with these biological functions has only recently been explored.Clinical reports,combined with neurotoxic lesioning,immunochemistry,neuronal activity recordings,and the polysomnographic analyses of genetically modified animals,have revealed that the PVH is important for the control of wakefulness.Here,we review emerging anatomical and neural mechanisms for sleep–wake regulation in the PVH to support its essential role in the promotion and maintenance of wakefulness.

关键词： Paraventricular nucleus of the hypothalamus sleep-wakeregulation circadianrhythm

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Giant intraventricular and Paraventricular cavernous malformations with multifocal subependymal cavernous malformations in pediatric patients: Two case reports

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World Journal of Radiology 2020年第2期12卷 10-17页

作者： Suwadee Eng-Chuan Supika Kritsaneepaiboon Anukoon Kaewborisutsakul Kanet Kanjanapradit Department of Radiology Faculty of MedicinePrince of Songkla UniversityHat Yai 90110Thailand Neurosugery Unit Department of SurgeryFaculty of MedicinePrince of Songkla UniversityHat Yai 90110Thailand Department of Pathology Faculty of MedicinePrince of Songkla UniversityHat Yai 90110Thailand

BACKGROUND Giant cavernous malformation(GCM)is rarely found in intraventricular or Paraventricular locations.CASE SUMMARY We present two cases of 6-mo and 21-mo boys with intraventricular and Paraventricular GCMs including a literature review focused on location and imaging findings.Characteristic magnetic resonance imaging findings such as multicystic lesions and a hemosiderin ring or bubbles-of-blood appearance can assist in the differential diagnosis of a hemorrhagic intraventricular and/or Paraventricular mass.CONCLUSION Multifocal intraventricular and/or Paraventricular GCM in small children is rare.The characteristic magnetic resonance imaging findings can help to differentiate GCMs from other intraventricular tumors.

关键词： Cavernous malformation Giant intraventricular Paraventricular Multifocal subependymal Children Case report

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Navigation-assisted transcortical transventricular approach for Paraventricular cavernoma:A technical note and review of the literature

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Laparoscopic, Endoscopic and Robotic Surgery 2018年第3期1卷 66-69页

作者： Xinwei Li Kun Wang Xueying Xu Yirong Wang Lutz Dorner Department of Neurosurgery Sir Run Run Shaw HospitalZhejiang University School of MedicineQingchun East Road 3Hangzhou 310016China Department of Neurosurgery Xiasha CampusSir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310020China Department of Neurosurgery Universit€atsklinikum Schleswig-HolsteinCampus KielArnold-Heller Straße 3Kiel 24105Germany

The surgery of Paraventricular cavernoma remains a challenge for the neurosurgeon.Few approaches have been specially described for Paraventricular cavernoma in literature.We present a patient with a symptomatic Paraventricular cavernoma in the dorsal portion of the right lateral ventricles roof causing ventricular hemorrhage,and review his surgical approaches.This patient underwent a navigationassisted transcortical transventricular approach resulting in a complete resection without any neurologic deficits.The approach allows a safe and effective resection of Paraventricular cavernomas.

关键词： Paraventricular Neuronavigation Cavernoma Transcortical transventricular approach

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Hypothalamic Paraventricular nucleus stimulation reduces intestinal injury in rats with ulcerative colitis

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World Journal of Gastroenterology 2016年第14期22卷 3769-3776页

作者： Quan-Jun Deng Ding-Jing Deng Jin Che Hai-Rong Zhao Jun-Jie Yu Yong-Yu Lu Department of Neurosurgery General Hospital Affiliated to Tianjin Medical University Department of Gastroenterology General Hospital Affiliated to Tianjin Medical University Department of Cerebral surgery people's Hospital of Haimen

AIM: To investigate the effect and mechanism of stimulation of the hypothalamic Paraventricular nucleus with glutamate acid in rats with ulcerative colitis(UC).METHODS: The rats were anesthetized with 10% chloral hydrate via abdominal injection and treated with an equal volume of TNBS + 50% ethanol enema, injected into the upper section of the anus with the tail facing up. Colonic damage scores were calculated after injecting a certain dose of glutamic acid into the Paraventricular nucleus(p VN), and the effect of the nucleus tractus solitarius(NTS) and vagus nerve in alleviating UC injury through chemical stimulation of the p VN was observed in rats. Expression changes of C-myc, Apaf-1, caspase-3, interleukin(IL)-6, and IL-17 during the protection against UC injury through chemical stimulation of the p VN in rats were detected by Western blot. Malondialdehyde(MDA) content and superoxide dismutase(SOD) activity in colon tissues of rats were measured by colorimetric methods. RESULTS: Chemical stimulation of the PVN significantly reduced UC in rats in a dose-dependent manner. The protective effects of the chemical stimulationof the p VN on rats with UC were eliminated after chemical damage to the p VN. After glutamate receptor antagonist kynurenic acid was injected into the p VN, the protective effects of the chemical stimulation of the p VN were eliminated in rats with UC. After AVpVl receptor antagonist([Deamino-penl, val4, D-Arg8]-vasopressin) was injected into NTS or bilateral chemical damage to NTS, the protective effect of the chemical stimulation of p VN on UC was also eliminated. After chemical stimulation of the p VN, SOD activity increased, MDA content decreased, C-myc protein expression significantly increased, caspase-3 and Apaf-1 protein expression significantly decreased, and IL-6 and IL-17 expression decreased in colon tissues in rats with UC. CONCLUSION: Chemical stimulation of the hypothalamic p VN provides a protective effect against UC injury in rats. Hypothalamic p VN, NTS and vagus nerve play k

关键词： Paraventricular nucleus Nucleus tractus solitarius Ulcerative colitis Arginine vasopressin 2,4,6-tri

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Fos expression　incatecholaminergic　medullary　neu-rons　induced　by　chemical　stimulation　of　stomach　projecting　to　the　Paraventricular　nucleus　of　hypothalamus　in　rats

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World Journal of Gastroenterology 1997年第2期3卷 15-17页

作者： DONG Yuan Xiang, XIONG Kang Hui, RAO Zhi Ren and SHI Ji Wu

Ｆｏｓｅｘｐｒｅｓｓｉｏｎｉｎｃａｔｅｃｈｏｌａｍｉｎｅｒｇｉｃｍｅｄｕｌａｒｙｎｅｕｒｏｎｓｉｎｄｕｃｅｄｂｙｃｈｅｍｉｃａｌｓｔｉｍｕｌａｔｉｏｎｏｆｓｔｏｍａｃｈｐｒｏｊｅｃｔｉｎｇｔｏｔｈｅｐａｒａｖｅｎｔ... 详细信息

Ｆｏｓｅｘｐｒｅｓｓｉｏｎｉｎｃａｔｅｃｈｏｌａｍｉｎｅｒｇｉｃｍｅｄｕｌａｒｙｎｅｕｒｏｎｓｉｎｄｕｃｅｄｂｙｃｈｅｍｉｃａｌｓｔｉｍｕｌａｔｉｏｎｏｆｓｔｏｍａｃｈｐｒｏｊｅｃｔｉｎｇｔｏｔｈｅｐａｒａｖｅｎｔｒｉｃｕｌａｒｎｕｃｌｅｕｓｏｆｈ...

关键词： medulla oblongata Paraventricular hypothalamic nucleus neurons immunochemistry

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