Neural Regeneration Research
·
2017
·
IF 1.769
Zhi-fang Zheng,Yi-shu Liu,Xuan Min,Jian-bing Tang,Hong-wei Liu,Biao Cheng
Local sympathetic denervation by surgical sympathectomy is used in the treatment of lower limb ulcers and ischemia, but the restoration of cutaneous sympathetic nerve functions is less clear. This study aims to explore the recovery of cutaneous sympathetic functions after bilateral L 2–4 sympathectomy. The skin temperature of the left feet, using a point monitoring thermometer, increased intraoperatively after sympathectomy. The cytoplasm of sympathetic neurons contained tyrosine hydroxylase and dopamine β-hydroxylase, visualized by immunofluorescence, indicated the accuracy of sympathectomy. Iodine starch test results suggested that the sweating function of the hind feet plantar skin decreased 2 and 7 weeks after lumbar sympathectomy but had recovered by 3 months. Immunofluorescence and western blot assay results revealed that norepinephrine and dopamine β-hydroxylase expression in the skin from the sacrococcygeal region and hind feet decreased in the sympathectomized group at 2 weeks. Transmission electron microscopy results showed that perinuclear space and axon demyelination in sympathetic cells in the L 5 sympathetic trunks were found in the sympathectomized group 3 months after sympathectomy. Although sympathetic denervation occurred in the sacrococcygeal region and hind feet skin 2 weeks after lumbar sympathectomy, the skin functions recovered gradually over 7 weeks to 3 months. In conclusion, sympathetic functional recovery may account for the recurrence of hyperhidrosis after sympathectomy and the normalization of sympathetic nerve trunks after incomplete injury. The recovery of sympathetic nerve function was slower in the limbs than in the torso after bilateral L 2–4 sympathectomy.
研究领域:
医学
·
神经科学
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DOI
PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2019
·Vol. 177
·期 3
·687-700
·
IF 6.583
Huihong Zeng,Huan Li,Mengzhen Yue,Ying Fan,Jiaoqi Cheng,Xincheng Wu,Rui Xu,Wuping Yang,Manjun Li,Jiahui Tang,Hongping Chen,Bohai Kuang,Guangqin Fan,Qingxian Zhu,Lijian Shao
Background and Purpose Damage to intestinal epithelial cells and mucosa limits the effectiveness of several anti-cancer chemotherapeutic agents but the underlying mechanism (s) remain unknown. Little is known of how enteric nervous system regulates proliferation, differentiation, impairment, and regeneration of intestinal stem cells. Here we have investigated the effects of isoprenaline on the damaged intestinal stem cells induced by chemotherapeutic treatments in mice. Experimental Approach The effects of inhibiting sympathetic and parasympathetic nerves on intestinal stem cells were examined in male C57BL/6J mice. Protection by isoprenaline of intestinal stem cells was assessed in the presence or absence of 5-fluorouracil (5FU) or cisplatin. Cellular apoptosis, cell cycle, PI3K/Akt signalling, and NF-κB signalling in intestinal stem cells were mechanistically evaluated. Key Results The sympathetic nerve inhibitor 6-OHDA decreased the number and function of intestinal stem cells. 5FU or cisplatin treatment damaged both intestinal stem cells and sympathetic nerves. Notably, isoprenaline accelerated the recovery of intestinal stem cells after 5FU or cisplatin treatment. This protective effect of isoprenaline on damaged intestinal stem cells was mediated by β 2 -adrenoceptors. The benefits of isoprenaline were mainly mediated by inhibiting cellular apoptosis induced by 5FU treatment, which might contribute to fine-tuning regulating NF-κB signalling pathway by isoprenaline administration. Conclusions and Implications Treatment with isoprenaline is a new approach to ameliorate the damage to intestinal stem cells following exposure to cancer chemotherapeutic agents.
研究领域:
药理学
·
肿瘤学
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胃肠病学
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神经科学
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产品关联
DOI
PubMed
高影响因子
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
·
2023
·Vol. 64
·期 12
·13-13
·
IF 4.4
Siyu He,Jun Liu,Yunxia Xue,Ting Fu,Zhijie Li
Purpose:This study aims to investigate the potential involvement of spleen-derived monocytes in the repair process following corneal epithelial abrasion.Methods:A corneal epithelial abrasion model was established in male C57BL/6J mice, and the dynamic changes of monocyte subpopulations in the injured cornea were analyzed using flow cytometry. The effects of Ly6Chimonocyte depletion and local adoptive transfer of purified Ly6Chimonocytes on wound closure and neutrophil recruitment to the injured cornea were observed. The effect of sympathetic nerves on the recruitment of spleen-derived Ly6Chimonocytes to the injured cornea was also investigated using multiple methods. The emigration of fluorescence-labeled monocytes to the injured cornea was validated through intravital microscopy. Finally, differential genes between different groups were identified through high-throughput RNA sequencing and analyzed for functional enrichment, followed by verification by quantitative PCR.Results:Ly6Chimonocytes were present in large numbers in the injured cornea prior to neutrophil recruitment. Predepletion of Ly6Chimonocytes significantly inhibited neutrophil recruitment to the injured cornea. Furthermore, surgical removal of the spleen significantly reduced the number of Ly6Chimonocytes in the injured cornea. Further observations revealed that sympathetic blockade significantly reduced the number of Ly6Chimonocytes recruited to the injured cornea. In contrast, administration of the β2-adrenergic receptor agonist significantly increased the number of Ly6Chimonocytes recruited to the injured cornea in animals treated with sympathectomy and catecholamine synthesis inhibition.Conclusions:Our results suggest that spleen-derived Ly6Chimonocytes, under the control of the sympathetic nervous system, play a critical role in the inflammatory response following corneal injury.
研究领域:
免疫学
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眼科学
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神经科学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2024
·
IF 8.7
Wenzhe Sun,Hongwei Lu,Pengqin Zhang,Lian Zeng,Bing Ye,Yi Xu,Jianan Chen,Peiran Xue,Jialin Yu,Kaifang Chen,Bin Wu,Xiao Lv,Xiaodong Guo,Yanzhen Qu
Severe burn injuries immediately trigger a sustained systemic and local stress response. During this process, the sympathetic nervous system releases large amounts of catecholamines, which bind to β-adrenergic receptors (β-AR) on cell membranes, negatively affecting skin regeneration. Additionally, recurrent bacterial infections make burn wounds difficult to treat, posing significant and ongoing challenges to burn care. To address these challenges, we pioneered the study of locally delivered propranolol for burn wound treatment, revealing its ability to antagonize norepinephrine (NE) and regulate the sympathetic nervous system. In this study, a Cu 2 ⁺-loaded anti-sympathetic hydrogel (copper ion cross-linked propranolol@gelatin/alginate, PNL@GA-Cu) was developed to remodel the challenging neuromodulatory microenvironment and accelerate the repair of the infected burn wound. The hydrogel system releases Cu 2 ⁺ and propranolol simultaneously during degradation, synergistically acting on local wound tissue. Cu 2 ⁺ exhibits dual effects of antibacterial activity and promoting angiogenesis, effectively killing Staphylococcus aureus and Escherichia coli while enhancing the expression of angiogenesis-related genes (CD31, VEGF). Meanwhile, propranolol can counteract the inhibitory effects of NE simulated chronic stress microenvironment on angiogenesis and mitigate sympathetic nerve innervation during the early stages of wound healing. Finally, the PNL@GA-Cu hydrogel significantly promoted the repair of third-degree full-thickness burns in SD rats. Approaches targeting the neural microenvironment for burn wound treatment has not been previously addressed in the literature. The anti-sympathetic PNL@GA-Cu hydrogel offers a promising strategy for treating infected burn wounds. Remodeling the neuromodulatory microenvironment could be an emerging strategy in tissue engineering.
研究领域:
组织工程
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伤口愈合
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药理学
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传染病学
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神经科学
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产品关联
DOI
PubMed
高影响因子
INFLAMMATION
·
2025
·
IF 5
Deng Qirui,Liu Xinyan,Wen Xiujuan,Huang Hao,Tang Hongfeng
The aim of this study was to investigate how ultraviolet B (UVB) light regulates AP-1 expression via the β2-adrenergic receptor (β2-AR) in epidermal keratinocytes, which in turn regulates melanin synthesis in melanocytes, thereby modulating downstream melanin production in skin hair follicles and altering mouse skin color. We established a UV-irradiated mouse model to investigate the effects of UV radiation on changes in skin color. By measuring changes in the expression of genes related to cutaneous sympathetic nerves, norepinephrine synthesis and melanin synthesis, we investigated the relationship between β2-AR expression and cutaneous melanogenesis and determined the localization of β2-AR in cells. The results of the siRNA-mediated transfection of keratinized cells with downregulated β2-AR expression were further verified in vitro. Our results suggest that UVB alters the color of the dorsal skin in mice by activating the AP-1/IL-6 pathway, which triggers the sympathetic release of norepinephrine, thereby increasing β2-AR expression in keratinocytes. Overall, our study improves the current understanding of how UVB light influences skin color changes and highlights the complex interplay between ultraviolet radiation and skin physiology.
研究领域:
皮肤病学
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分子生物学
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神经科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-19
·
IF 10.6
Jiang Mingzhou,Zhu Zhidong,Zhou Ziyu,Yan Zhiqiang,Huang Kai,Jiang Rongrong,Fan Xi,Jieensi Milayi,Pang Liewen,Wang Yiqing,Sun Xiaotian
Background Cardiovascular events secondary to stroke–collectively classified as stroke-heart syndrome–greatly impair the patient’s prognosis, however its underlying mechanism has yet to be determined. To investigate the mechanism of central neuroinflammation and its effects on stroke-heart syndrome, a temperature-ultrasound responsive brain-targeted drug delivery system, DATS/MION-LPE, was synthesized to specifically study neuroinflammation in the mouse middle cerebral artery occlusion (MCAO) model.Results The specific polymer of DATS/MION-LPE can close the nanoparticle pores at 37 °C, restricting drug release in the circulation. After the nanoparticles were targeted to brains, the polymer can be cleaved under external ultrasound irradiation, reopening the nanoparticle pores and allowing drug release, therefore directly managing the neuroinflammation. After a stroke, a significant cerebral inflammation occurred, with elevated IL-1β and pyrin domain-containing 3 (NLRP3) inflammasome. Accordingly, significantly increased histone deacetylase 6 (HDAC6) and decreased sirtuin 1 (SIRT1) were observed. An antagonistic relationship between HDAC6 and SIRT1 was found, which can jointly regulate the cerebral NLRP3 expression. The systemic IL-1β and ATP levels were increased after the stroke, accompanied by a significant heart injury including contractile dysfunction, elevated IL-1β levels, and oxidative stress. Meanwhile, neuroinflammation can trigger sympathetic nervous overexcitation with associated heart damage. DATS/MION-LPE can targetedly effect on ischemic brain, exhibiting cerebral and cardiac protective effects including downregulated cerebral NLRP3 and HDAC6 expressions, upregulated SIRT1 expressions in brain, reduced IL-1β and ATP in circulation, and alleviated cardiac impairment.Conclusion This study introduced the key role of neuroinflammation in stroke-heart syndrome and first investigated the crucial HDAC6/SIRT1-NLRP3 circuit in this process. Heart injury secondary to stroke is mediated by neuroinflammation induced systemic inflammatory responses and sympathoexcitation. DATS/MION-LPE is a unique tool and effective therapeutic agent, which provides new insights into combinational heart and cardiac protection.Graphical Abstract
研究领域:
神经科学
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心血管疾病
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药物递送系统
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炎症
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分子生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR ENDOCRINOLOGY
·
2024
·
IF 3.8
Zhaoqing Xi,Ling Shu,Lingling Xiao,Xuesheng Fang,Mingyan Dai,Jing Wang,Yuan Wu,Junxia Zhang,Mingwei Bao
Obesity-associated cardiac remodeling is characterized by cardiac sympathetic nerve over-activation and pro-inflammatory macrophage infiltration. We identified norepinephrine (NE), a sympathetic neurotransmitter, as a pro-inflammatory effector to activate macrophage NLRP3 inflammasome, which contributed to cardiac inflammation. In vivo, Sprague-Dawley (SD) rats were fed a high-fat diet (HFD) for 12 weeks to establish obese rat models. Obese rats exhibited marked cardiac hypertrophy compared to the normal rats. The expression of NLRP3 and interleukin (IL)-1β was upregulated, accompanied by CD68 + NLRP3 + macrophages infiltration in hearts of the obese rats. The obese rats also showed increased sympathetic nerve activity. β-adrenergic receptor (AR) inhibition mitigated these changes. In vitro, sympathetic neurotransmitter NE significantly exacerbated palmitic acid (PA)-induced macrophage polarization toward pro-inflammatory type and NLRP3 inflammasome activation in THP-1 macrophages. It was further found that the pro-inflammatory role of NE is dependent on the activation of protein kinase A (PKA) and subsequently inhibition of β-arrestin2, which is an important regulator of nuclear factor-kappa B (NF-κB) pathway. This study identifies the neuro-immune axis as an important mediator in obesity-associated cardiac remodeling. Targeting the neuro-immune system may open therapeutic opportunities for the treatment of cardiac remodeling in obesity.
研究领域:
心脏病学
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免疫学
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神经科学
·
药理学
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产品关联
DOI
PubMed
高影响因子
Small
·
2024
·
IF 13
Heng Lin,Hengyang Liu,Haosong Xi,Dangwei Li,Pengcheng Jiang,Yijun Wang,Siyi Cheng,Hong Jiang,Hongbing Deng,Xue Zhou,Lilei Yu
The occurrence of myocardial infarction (MI)-induced malignant ventricular arrhythmias (VAs) is closely associated with the hyperactivation of left stellate ganglion (LSG). Proinflammatory M1 macrophage is reported to aggravate sympathetic overactivation and cause VAs. Therefore, the depletion of M1 macrophage is anticipated to inhibit LSG overactivation and alleviate MI-induced VAs. Herein, oxygen-independent photodynamic therapy (Oi-PDT) combined with M1 macrophage targeting is applied to selectively deplete M1 macrophage in LSG and further treat MI-induced VAs. Oi-PDT, which overcomes the limitation of extremely dependence on oxygen content in traditional PDT, is constructed through the generation of oxidizing photogenerated holes (h + ) under the irradiation of near-infrared (NIR) light on the prepared Oi-PDT agent (PPSCD). Meanwhile, PPSCD targets M1 macrophage through conjunction with SR-A receptor. The selective consumption of M1 macrophage is attributed to both apoptosis and ferroptosis induced by h + , 1 O 2 , and O 2 •− generated in Oi-PDT. In vivo tests indicated neural activity experienced a notable reduction from 104.5 ± 2.9 to 51.5 ± 6.7 after MI with Oi-PDT treatment, thereby significantly inhibited VAs. The implementation of this study provides a promising strategy for selective consumption of M1 macrophages and treatment of VAs induced by MI.
研究领域:
心脏病学
·
免疫学
·
神经科学
·
治疗诊断学
✓ 已验证
DOI
PubMed
高影响因子
IMMUNITY
·
2024
·
IF 25.5
Bo Wei,Guo Cheng,Qianqian Bi,Cheng Lu,Qihang Sun,Li Li,Ningting Chen,Miner Hu,Haoran Lu,Xuancheng Xu,Genxiang Mao,Shu Wan,Zhechun Hu,Yan Gu,Jiaxin Zheng,Li Zhao,Xiao Z. Shen,Xiaoli Liu,Peng Shi
Hypertension is usually accompanied by elevated sympathetic tonicity, but how sympathetic hyperactivity is triggered is not clear. Recent advances revealed that microglia-centered neuroinflammation contributes to sympathetic excitation in hypertension. In this study, we performed a temporospatial analysis of microglia at both morphological and transcriptomic levels and found that microglia in the hypothalamic paraventricular nucleus (PVN), a sympathetic center, were early responders to hypertensive challenges. Vasculature analyses revealed that the PVN was characterized by high capillary density, thin vessel diameter, and complex vascular topology relative to other brain regions. As such, the PVN was susceptible to the penetration of ATP released from the vasculature in response to hemodynamic disturbance after blood pressure increase. Mechanistically, ATP ligation to microglial P2Y12 receptor was responsible for microglial inflammatory activation and the eventual sympathetic overflow. Together, these findings identified a distinct vasculature pattern rendering vulnerability of PVN pre-sympathetic neurons to hypertension-associated microglia-mediated inflammatory insults.
研究领域:
神经科学
·
心血管研究
·
免疫学
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产品关联
DOI
PubMed
高影响因子
OncoTargets and Therapy
·
2019
·
IF 3.046
Chao Ma,Tao Gao,Jun Ju,Yi Zhang,Qianwei Ni,Yun Li,Zhenyan Zhao,Juan Chai,Xiangming Yang,Moyi Sun
Purpose Perineural invasion (PNI) is reported to correlate with local recurrence and poor prognosis of salivary adenoid cystic carcinoma (SACC). However, the pathogenesis of PNI remains unclear. The aims of this study were to investigate the correlation between sympathetic innervation and SACC PNI and to elucidate how the sympathetic neurotransmitter norepinephrine (NE) regulates the PNI process. Materials and methods Sympathetic innervation and β2-adrenergic receptor (β2-AR) expression in SACC tissues were evaluated by immunohistochemistry. The NE concentrations in SACC tissues and dorsal root ganglia (DRG) coculture models were measured by ELISA. β2-AR expression in SACC cells was detected by performing quantitative real-time polymerase chain reaction (qRT-PCR) and immunofluorescence assay. SACC cells were treated with NE, the nonselective α-AR blocker phentolamine, the β2-AR antagonist ICI118,551, or were transfected with β2-AR small interfering RNA (siRNA). Proliferation was evaluated in methyl thiazolyl tetrazolium assay, and migration was evaluated in Transwell assay and wound-healing assay. PNI was tested through both Transwell assay and a DRG coculture model. The expressions of epithelial–mesenchymal transition (EMT) markers and matrix metalloproteinases (MMPs) were measured by performing qRT-PCR and Western blot assay. Results Sympathetic innervation and β2-AR were highly distributed in SACC tissues and correlated positively with PNI ( P =0.035 and P =0.003, respectively). The sympathetic neurotransmitter NE was overexpressed in SACC tissues and DRG coculture models. Exogenously added NE promoted proliferation, migration, and PNI of SACC cells via β2-AR activation. NE/β2-AR signaling may promote proliferation, migration, and PNI by inducing EMT and upregulating MMPs. However, β2-AR inhibition with either an antagonist or siRNA abrogated NE-induced PNI. Conclusion Collectively, our findings reveal the supportive role of sympathetic innervation in the pathogenesis of SACC PNI and suggest β2-AR as a potential therapeutic target for treating PNI in SACC.
研究领域:
肿瘤学
·
神经科学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Reports Medicine
·
2024
·
IF 11.7
Huidi Wang,Jie Li,Guangyan Wu,Xiaofei Lin,Jiaying Chen,Jingru Liang,Jiahui Zhang,Xiaoxia Luo,Hongyun Mao,Jiahui Xie,Zhuang Li,Hongwei Zhou,Kaiyu Xu,Jia Yin,Yan He
The gut permeability significantly increases after ischemic stroke, partly due to disrupted mucosal barrier, but the mechanism remains elusive. Here, we found that the mucus disruption starts at 2 h post stroke, whereas goblet cell functions remain intact. Meanwhile, the flagellated bacteria Helicobacter thrives and penetrates in the mucus layer. Elimination of the mucosal microbiota or transplantation of Helicobacter in germ-free mice reveals an important role of the mucosal microbiota in mucus disruption. The bacterial invasion is due to downregulated Toll-like receptor 5 (TLR5) and its downstream products flagellin-specific IgA and antimicrobial peptides. Knockdown of intestinal TLR5 increases the abundance of flagellated bacteria and exacerbates mucus injury. Intestinal TLR5 is downregulated by the activation of sympathetic nerve. Serum noradrenaline level is positively associated with flagellin level in patients with stroke and patients’ prognosis. These findings reveal a neural pathway in which the sympathetic nerve disrupts the mucosal barrier, providing potential therapeutic targets for stroke injury.
研究领域:
神经科学
·
免疫学
·
胃肠病学
·
微生物学
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产品关联
DOI
PubMed
高影响因子
Neural Regeneration Research
·
2025
·
IF 6.7
Gu Xinyi,Huang Chen,Wang Shen,Deng Jin,Guo Shuhang,Yin Xiaofeng
To perform various functions in the body, skeletal muscle is controlled and coordinated as a whole by nerves. However, there has been little research into whether the nerve control characteristics of different muscles are different, and the importance of these potential differences. In the present study, we used a three-dimensional imaging of solvent-cleared organ-compatible multi-tracer technique to explore the spatial distribution patterns of sensory and sympathetic neurons that innervate limb muscles. We integrated transcriptome sequencing datasets from mouse limb muscles in public databases and performed correlation analysis with neuronal spatial distribution data to reveal the unique effects of different types of neurons on muscle functional pathways. In terms of spatial distribution patterns, sympathetic neurons exhibited a more concentrated distribution than sensory and motor neurons. In addition, the neuronal innervation of limb muscles exhibited four different characteristics: sympathetic neuron-rich muscle, sensory neuron-rich muscle, neuron-sparse muscle, and motor neuron-rich muscle. Sensory neuron density was mainly associated with muscle contractile structure and cell pH, whereas sympathetic neuron density was associated with protein kinase activity, muscle vasculature, muscle calcium-dependent protein kinase activity, lipid transport, and vesicle release. Motor neuron density was mainly associated with protein kinase activity, cell adhesion, oxidoreductase activity, and exocytosis. These findings may contribute to a deeper understanding of how nerves cooperate to endow muscles with diverse physiological functions, thereby providing new insights and experimental evidence for the treatment of various neuromuscular diseases.
研究领域:
神经科学
·
肌肉生理学
·
系统生物学
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分子生物学
·
解剖学
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产品关联
DOI
PubMed
高影响因子
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