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Neuroscience Bulletin 2023年第9期39卷 1363-1374页

作者： Debora Denardin Luckemeyer Wenrui Xie Arthur Silveira Prudente Katherine A.Qualls Raquel Tonello Judith A.Strong Temugin Berta Jun-Ming Zhang Pain Research Center Department of AnesthesiologyUniversity of Cincinnati College of MedicineCincinnatiOH45267USA Department of Molecular Pathobiology Department of Neuroscience and PhysiologyNeuroscience InstituteNew York UniversityNew YorkNY10010USA

Although sympathetic blockade is clinically used to treat pain,the underlying mechanisms remain unclear.We developed a localized microsympathectomy(mSYMPX),by cutting the grey rami entering the spinal nerves near the rodent lumbar dorsal root ganglia(DRG).In a chemotherapy-induced peripheral neuropathy model,mSYMPX attenuated pain behaviors via DRG macrophages and the anti-inflammatory actions of transforming growth factor-β(TGF-β)and its receptor TGF-βR1.Here,we examined the role of TGF-βin sympathetic-mediated radiculopathy produced by local inflammation of the DRG(LID).Mice showed mechanical hypersensitivity and transcriptional and protein upregulation of TGF-β1 and TGF-βR1 three days after LID.Microsympathectomy prevented mechanical hypersensitivity and further upregulated Tgfb1 and Tgfbr1.Intrathecal delivery of TGF-β1 rapidly relieved the LID-induced mechanical hypersensitivity,and TGF-βR1 antagonists rapidly unmasked the mechanical hypersensitivity after LID+mSYMPX.In situ hybridization showed that Tgfb1 was largely expressed in DRG macrophages,and Tgfbr1 in neurons.We suggest that TGF-βsignaling is a general underlying mechanism of local sympathetic blockade.

关键词： TGF-β sympathetic Radiculopathy:Inflammation Cytokine

Impaired Hypothalamic Regulation of sympathetic Outflow in Primary Hypertension

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Neuroscience Bulletin 2019年第1期35卷 124-132页

作者： Jing-Jing Zhou Hui-Jie Ma Jian-Ying Shao Hui-Lin Pan De-Pei Li Division of Anesthesiology and Critical Care The University of Texas MD Anderson Cancer Center Department of Physiology Hebei Medical University Department of Medicine Center for Precision MedicineUniversity of Missouri

The hypothalamic paraventricular nucleus(PVN) is a crucial region involved in maintaining homeostasis through the regulation of cardiovascular, neuroendocrine, and other functions. The PVN provides a dominant source of excitatory drive to the sympathetic outflow through innervation of the brainstem and spinal cord in hypertension. We discuss current findings on the role of the PVN in the regulation of sympathetic output in both normotensive and hypertensive conditions. The PVN seems to play a major role in generating the elevated sympathetic vasomotor activity that is characteristic of multiple forms of hypertension, including primary hypertension in humans. Recent studies in the spontaneously hypertensive rat model have revealed an imbalance of inhibitory and excitatory synaptic inputs to PVN presympathetic neurons as indicated by impaired inhibitory and enhanced excitatory synaptic inputs in hypertension.This imbalance of inhibitory and excitatory synaptic inputs in the PVN forms the basis for elevated sympathetic outflow in hypertension. In this review, we discuss the disruption of balance between glutamatergic and GABAergic inputs and the associated cellular and molecular alterations as mechanisms underlying the hyperactivity of PVN pre-sympathetic neurons in hypertension.

关键词： Hypothalamus Paraventricular nucleus Synaptic plasticity Essential hypertension sympathetic nervous system

Angiotensin-Converting Enzyme 2 in the Rostral Ventrolateral Medulla Regulates Cholinergic Signaling and Cardiovascular and sympathetic Responses in Hypertensive Rats

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Neuroscience Bulletin 2019年第1期35卷 67-78页

作者： Yu Deng Xing Tan Miao-Ling Li Wei-Zhong Wang Yang-Kai Wang Department of Physiology Second Military Medical UniversityShanghai 200433China Institution of Polar Medicine Research Center Second Military Medical UniversityShanghai 200433China Department of Anesthesiology Changhai HospitalShanghai 200433China Institute of Cardiovascular Medical Research Southwest Medical UniversityLuzhou 646000China

The rostral ventrolateral medulla(RVLM) is a key region in cardiovascular regulation. It has been demonstrated that cholinergic synaptic transmission in the RVLM is enhanced in hypertensive rats. Angiotensinconverting enzyme 2(ACE2) in the brain plays beneficial roles in cardiovascular function in hypertension. The purpose of this study was to determine the effect of ACE2 overexpression in the RVLM on cholinergic synaptic transmission in spontaneously hypertensive rats(SHRs).Four weeks after injecting lentiviral particles containing enhanced green fluorescent protein and ACE2 bilaterally into the RVLM, the blood pressure and heart rate were notably decreased. ACE2 overexpression significantly reduced the concentration of acetylcholine in microdialysis fluid from the RVLM and blunted the decrease in blood pressure evoked by bilateral injection of atropine into the RVLM in SHRs. In conclusion, we suggest that ACE2 overexpression in the RVLM attenuates the enhanced cholinergic synaptic transmission in SHRs.

关键词： Hypertension Renin-angiotensin system Gene transfer Acetylcholine sympathetic nerve activity

Inflammatory Changes in Paravertebral sympathetic Ganglia in Two Rat Pain Models

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Neuroscience Bulletin 2018年第1期34卷 85-97页

作者： Ai-Ling Li Jing-Dong Zhang Wenrui Xie Judith A. Strong Jun-Ming Zhang Department of Anesthesiology University of Cincinnati College of Medicine Cincinnati OH 45267 USA Department of Psychological and Brain Science Indiana University Bloomington 702 N Walnut Grove Ave. Bloomington IN 47405 USA

Injury to peripheral nerves can lead to neuropathic pain, along with well-studied effects on sensory neurons, including hyperexcitability, abnormal spontaneous activity, and neuroinflammation in the sensory ganglia. Neuropathic pain can be enhanced by sympathetic activity. Peripheral nerve injury may also damage sympathetic axons or expose them to an inflammatory environment. In this study, we examined the lumbar sympathetic ganglion responses to two rat pain models： ligation of the L5 spinal nerve, and local inflammation of the L5 dorsal root ganglion （DRG）, which does not involve axotomy. Both models resulted in neuroinflammatory changes in the sympathetic ganglia, as indicated by macrophage responses, satellite glia activation, and increased numbers of T cells, along with very modest increases in sympathetic neuron excitability （but not spontaneous activity） measured in ex vivo recordings. The spinal nerve ligation model generally caused larger responses than DRG inflammation. Plasticity of the sympathetic system should be recognized in studies of sympathetic effects on pain.

关键词： Neuropathic pain sympathetic Macrophage T cell Satellite glia Inflammation Hyperexcitability

Role of sympathetic and parasympathetic nerves in the development of gastric cancer through antagonism

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Chinese Medical Journal 2021年第8期134卷 908-909页

作者： Jing Gao Shu-Gang Liu Traditional Chinese Medicine Department The Fourth Hospital of Hebei Medical UniversityShijiazhuangHebei 050011China.

Previous studies have shown that the autonomic nervous system plays a role in the occurrence and development of gastric cancer(GC).[1-3]sympathetic and parasympathetic nerve fibers constitute a network in gastric wall submucosa and muscularis to control gastric peristalsis and secretion.These two groups of nerve fibers antagonize and coordinate with each other under the regulation of the central nervous system to complete their innervation function.Currently,most of the studies on the autonomic nervous system and GC focus on a single species nerve fiber or transmitter.The present study aimed to elucidate how the sympathetic and parasympathetic nervous systems antagonize and coordinate in the occurrence and development of GC.Simultaneously,some gastrointestinal hormones are also identified in the development of GC as helpers or tools of the sympathetic or parasympathetic nervous system.

关键词： sympathetic gastric cancer

Electroacupuncture at ST36 modulates gastric motility via vagovagal and sympathetic reflexes in rats

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World Journal of Gastroenterology 2019年第19期25卷 2315-2326页

作者： Meng-Jiang Lu Zhi Yu Yan He Yin Yin Bin Xu Key Laboratory of Acupuncture and Medicine Research of Ministry of Education Nanjing University of Chinese Medicine

BACKGROUND Electroacupuncture(EA) at ST36 can significantly improve gastrointestinal symptoms, especially in promoting gastrointestinal motility. The automatic nervous system plays a main role in EA, but few studies exist on how vagovagal and sympathetic reflexes affect EA to regulate gastrointestinal motility.AIM To study the role of vagovagal and sympathetic reflexes in EA at ST36, as well as the associated receptor subtypes that are involved.METHODS Gastric motility was measured with a manometric balloon placed in the gastric antrum area in anesthetized animals. The peripheral nervous discharge was measured using a platinum electrode hooking the vagus or greater splanchnic nerve, and the central nervous discharge was measured with a glass microelectrode in the dorsal motor nucleus of the vagus(DMV). The effects and mechanisms of EA at ST36 were explored in male Sprague-Dawley rats which were divided in to a control group, vagotomy group, sympathectomy group, and microinjection group [including an artificial cerebrospinal fluid group, glutamate(L-Glu) group, and γ-aminobutyric acid(GABA) group] and in genetically modified male mice [β1β2 receptor-knockout(β1β2^(-/-)) mice, M2M3 receptorknockout(M2M3^(-/-)) mice, and wild-type control mice].RESULTS EA at ST36 promoted gastric motility during 30-120 s. During EA, both vagus and sympathetic nerve discharges increased, with a much higher frequency of vagus nerve discharge than sympathetic discharge. The gastric motility mediated by EA at ST36 was interdicted by vagotomy. However, gastric motility mediated by EA at ST36 was increased during 0-120 s by sympathectomy, which eliminated the delay effect of EA during 0-30 s, but it was lower than the control group during 30-120 s. Using gene knockout mice and their wild-type controls to explore the receptor mechanisms, we found that EA at ST36 decreased gastric motility in M2/3^(-/-) mice, and promoted gastric motility in β1/2^(-/-) mice. Extracellular recordings showed that EA at ST36 increased spikes of the DMV. Microi

关键词： Gastric motility Electroacupuncture Vagovagal reflex sympathetic nerve Rats

The effects of hyperbaric oxygen therapy on paroxysmal sympathetic hyperactivity after cardiopulmonary resuscitation: a case series

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World Journal of Emergency Medicine 2023年第6期14卷 477-480页

作者： Hongyu Wang Yihao Li Meng Zhao Caihong Ren Sisen Zhang Department of Emergency Medicine the Fifth Clinical Medical College of Henan University of Chinese MedicineZhengzhou 450003China Department of Emergency Medicine People's Hospital of Henan Universityof Chinese Medicine/People's Hospitalof ZhengzhouZhengzhou 450003China Henan Research Centre of Cardiopulmonary-Cerebral Resuscitation Engineering Technology Zhengzhou 450003China Department of Emergency Medicine Luohe Central HospitalLuohe 462000China

The onset of cardiac arrest (CA) is sudden and critical.Due to cerebral ischaemia and hypoxia, the prognosis for post-cardiopulmonary resuscitation (CPR) patients is poor. Paroxysmal sympathetic hyperexcitability (PSH) is a potentially life-threatening condition, which is characterized by episodes of increased heart rate and blood pressure,sweating, hypothermia, and forced posture.[1] Hypoxicischaemic encephalopathy post-CPR can lead to PSH,which often indicates a worse prognosis.

关键词： sympathetic resuscitation prognosis

Short-term Safety and Efficiency of Cryoablation for Rena sympathetic Denervation in a Swine Model

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Chinese Medical Journal 2015年第6期128卷 790-794页

作者： Meng Ji Li Shen Yi-ZheWu Zhi-Feng Yao Jia-Sheng Yin Jia-Hui Chen Jian-Guo Jia Ling-Juan Qiao Peng LiD Jun-Bo Ge Institutes of Biomedical Science Fudan University Shanghai 200032 China Department of Cardiology Zhongshan Hospital Fudan University Shanghai 200032 China Cyrofocus Medtech Corporation Shanghai 200120 China

Background:Renal sympathetic nerves are involved in the reflective activation of the sympathetic nervous system in circulatory control.Catheter-based renal denervation (RDN) ameliorated treatment-resistant hypertension safely,but 10％-20％ of treated patients are nonresponders to radiofrequency denervation.The purpose of this study was to investigate the safety and efficiency of cryoablation for sympathetic denervation in a swine model and to explore a new way of RDN.Methods:Seven swines randomly assigned to two groups:Renal cryoablation (CR) group and control group.The control group underwent renal angiogram only.The CR group underwent renal angiogram plus bilateral renal cryoablation.Renal angiograms via femoral were performed before denervation,after denervation and prior to the sacrifice to access the diameter of renal arterial and the pressure of aorta abdominalis.Euthanasia of the swine was performed on 28-day to access norepinephrine (NE) changes of the renal cortex and the changes of renal nerves.Results:Cryoablation did not induce severe complications at any time point.There was no significant change in diameter of renal artery.CR reduced systolic blood pressure (BP) from 145.50 ± 9.95 mmHg at baseline to 119.00 ± 14.09 mmHg.There was a slight but insignificant decrease in diastolic BP.The main nerve changes at 28-day consisted of necrosis with perineurial fibrosis at the site of CR exposure in conjunction with the nerve vacuolation.Compared with the control group,renal tissue NE of CR group decreased by 89.85％.Conclusions:Percutaneous catheter-based cryoablation of the renal artery is safe.CR could effectively reduce NE storing in the renal cortex,and the efficiency could be maintained 28-day at least.

关键词： Cryoablation Renal sympathetic Denervation sympathetic Nerve System

Electroacupuncture at ST25 inhibits jejunal motility:Role ofsympathetic pathways and TRPV1

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World Journal of Gastroenterology 2016年第5期22卷 1834-1843页

作者： Zhi Yu Na Zhang Chun-Xia Lu Ting-Ting Pang Kai-Yue Wang Jing-Feng Jiang Bing Zhu Bin Xu Key Laboratory of Integrated Acupuncture and Drugs Nanjing University of Chinese MedicineNanjing 210023Jiangsu ProvinceChina Institute of Acupuncture and Moxibustion China Academy of Chinese Medical SciencesBeijing 100700China

AIM: To investigate whether electroacupuncture(EA) at ST25 affects jejunal motility in vivo and if so, whether a sympathetic pathway is involved.METHODS: Jejunal motility was assessed using a manometric balloon placed in the jejunum approximately about 3-5 cm away from the suspensory ligament of the duodenum in anesthetized animals. The effects of EA at ST25 were measured in male Sprague-Dawley rats, some of which were treated with propranolol or clenbuterol(EA intensities: 1, 3, 5, 7, and 9 m A), and in male transient receptor potential vanilloid-1(TRPV1)(capsaicin receptor) knockout mice(EA intensities: 1, 2, and 4 m A).RESULTS: Anesthetized rats exhibited three types of fasting jejunal motor patterns(types A, B, and C), and only type C rats responded to EA stimulation. In type C rats, EA at ST25 significantly suppressed the motor activity of the jejunum in an intensity-dependent manner. The inhibitory effect of EA was weakened by propranolol(β adrenoceptor antagonist) and disappeared with clenbuterol(β adrenoceptor agonist) induced inhibition of motility, suggesting that the effect of EA on motility is mediated via a sympathetic pathway. Compared with wild-type mice, EA at ST25 was less effective in TRPV1 knockout mice, suggesting that this multi-modal sensor channel participates in the mechanism. CONCLUSION: EA at ST25 was found to inhibit jejunal motility in an intensity-dependent manner, via a mechanism in which sympathetic nerves and TRPV1 receptors play an important role.

关键词： Gastrointestinal disorder Jejunal motility Electroacupuncture sympathetic nervous system Transient receptor potential vanilloid-1

Renal sympathetic denervation in resistant hypertension

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World Journal of Cardiology 2013年第4期5卷 94-101页

作者： Mário Santos Henrique Carvalho Cardiology Department Hospital Santo AntónioLargo Professor Abel Salazar4099-001 PortoPortugal

Resistant hypertension remains a major clinical problem despite the available multidrug therapy.Over the next decades,its incidence will likely increase given that it is strongly associated with older age and obesity.Resistant hypertension patients have an increased cardiovascular risk,thus effective antihypertensive treatment will provide substantial health benefits.The crosstalk between sympathetic nervous system and kidneys plays a crucial role in hypertension.It influences several pathophysiological mechanisms such as the central sympathetic tone,the sodium balance and the systemic neurohumoral activation.In fact,studies using several animal models demonstrated that the renal denervation prevented and attenuated hypertension in multiple species.Large reductions in blood pressure were also observed in malignant hypertension patients submitted to sympathectomy surgeries.However,these approaches had an unacceptably high rates of periprocedural complications and disabling adverse events.Recently,an innovative non-pharmacological therapy that modulates sympathetic activation has been successfully developed.Renal sympathetic percutaneous denervation is an endovascular procedure that uses radiofrequency energy to destroy the autonomic renal nerves running inside the adventitia of renal arteries.This method represents a promising new approach to the strategy of inhibiting the sympathetic nervous system.The aim of this review is to examine the background knowledge that resulted in the development of this hypertension treatment and to critically appraise the available clinical evidence.

关键词： Arterial hypertension sympathetic activity Renal denervation Percutaneous ablation Resistant hypertension