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Targeting neural reflex circuits in immunity to treat kidney disease
Nature Reviews Nephrology ( IF 41.5 ) Pub Date :  , DOI: 10.1038/nrneph.2017.132
Mark D. Okusa , Diane L. Rosin , Kevin J. Tracey

Neural pathways regulate immunity and inflammation via the inflammatory reflex and specific molecular targets can be modulated by stimulating neurons. Neuroimmunomodulation by nonpharmacological methods is emerging as a novel therapeutic strategy for inflammatory diseases, including kidney diseases and hypertension. Electrical stimulation of vagus neurons or treatment with pulsed ultrasound activates the cholinergic anti-inflammatory pathway (CAP) and protects mice from acute kidney injury (AKI). Direct innervation of the kidney, by afferent and efferent neurons, might have a role in modulating and responding to inflammation in various diseases, either locally or by providing feedback to regions of the central nervous system that are important in the inflammatory reflex pathway. Increased sympathetic drive to the kidney has a role in the pathogenesis of hypertension, and selective modulation of neuroimmune interactions in the kidney could potentially be more effective for lowering blood pressure and treating inflammatory kidney diseases than renal denervation. Use of optogenetic tools for selective stimulation of specific neurons has enabled the identification of neural circuits in the brain that modulate kidney function via activation of the CAP. In this Review we discuss evidence for a role of neural circuits in the control of renal inflammation as well as the therapeutic potential of targeting these circuits in the settings of AKI, kidney fibrosis and hypertension.

中文翻译:

针对神经反射回路的免疫力,以治疗肾脏疾病

神经途径通过炎症反射调节免疫力和炎症,特定的分子靶标可以通过刺激神经元来调节。通过非药理学方法进行的神经免疫调节正在作为炎症性疾病(包括肾脏疾病和高血压)的一种新型治疗策略出现。迷走神经元的电刺激或脉冲超声治疗可激活胆碱能抗炎途径(CAP),并保护小鼠免受急性肾损伤(AKI)。传入和传出神经元对肾脏的直接神经支配可能在局部或通过向炎症反射途径中重要的中枢神经系统区域提供反馈,从而对各种疾病中的炎症进行调节和响应。对肾脏的交感神经驱动作用与高血压的发病机制有关,与肾脏去神经支配相比,肾脏中神经免疫相互作用的选择性调节可能更有效地降低血压和治疗炎症性肾脏疾病。通过使用光遗传学工具选择性刺激特定的神经元,已经能够识别大脑中通过CAP激活来调节肾脏功能的神经回路。在这篇综述中,我们讨论了神经回路在控制肾脏炎症中的作用以及在AKI,肾纤维化和高血压中针对这些回路的治疗潜力的证据。肾脏中神经免疫相互作用的选择性调节可能比肾脏神经支配更有效地降低血压和治疗炎症性肾脏疾病。通过使用光遗传学工具选择性刺激特定的神经元,已经能够识别大脑中通过CAP激活来调节肾脏功能的神经回路。在这篇综述中,我们讨论了神经回路在控制肾脏炎症中的作用以及在AKI,肾纤维化和高血压中针对这些回路的治疗潜力的证据。肾脏中神经免疫相互作用的选择性调节可能比肾脏神经支配更有效地降低血压和治疗炎症性肾脏疾病。通过使用光遗传学工具选择性刺激特定的神经元,已经能够识别大脑中通过CAP激活来调节肾脏功能的神经回路。在这篇综述中,我们讨论了神经回路在控制肾脏炎症中的作用以及在AKI,肾纤维化和高血压中针对这些回路的治疗潜力的证据。通过使用光遗传学工具选择性刺激特定的神经元,已经能够识别大脑中通过CAP激活来调节肾脏功能的神经回路。在这篇综述中,我们讨论了神经回路在控制肾脏炎症中的作用以及在AKI,肾纤维化和高血压中针对这些回路的治疗潜力的证据。通过使用光遗传学工具选择性刺激特定的神经元,已经能够识别大脑中通过CAP激活来调节肾脏功能的神经回路。在这篇综述中,我们讨论了神经回路在控制肾脏炎症中的作用以及在AKI,肾纤维化和高血压中针对这些回路的治疗潜力的证据。
更新日期:2017-10-11
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