Neuroimmune mechanisms underlying electroacupuncture effect on vascular function

电针影响血管功能的神经免疫机制

基本信息

  • 批准号:
    10316925
  • 负责人:
  • 金额:
    $ 67.99万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-08-16 至 2026-07-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY Hypertension (HTN) is the most significant modifiable risk factor for cardiovascular disease and involves multiple pathways including those in the neuroendocrine and immune systems. Antihypertensive drugs manage HTN but do not address the central sympathetic and inflammatory pathways and approximately 50% of hypertensive (HTNive) patients do not have their blood pressure (BP) controlled. The World Health Organization has suggested acupuncture for HTN; however, prior clinical trials utilizing acupuncture have shown modest or null outcomes and not achieved clinically meaningful reductions in BP. These conflicting outcomes result from the lack of a mechanistic-based approach to using electroacupuncture (EA), a form of neurostimulation. The reasons for inadequate treatment and BP control are complex, but one reason for this therapeutic misalignment may be an incomplete understanding of the mechanisms underlying the development and progression of HTN including autonomic dysfunction and resulting low-grade inflammation. Using neuroanatomical mapping, phenotyping, and recording of neurophysiological responses that correspond to neuromodulatory mechanisms underlying effects of EA, we successfully selected specific acupoints that in combination (or combined (c)EA) show complementary mechanisms of sympathoinhibition and parasympathoexcitation and not only reduce BP to clinically meaningful levels but also improve underlying autonomic dysfunction and low-grade inflammation. Our proposed study addresses one of NCCIH’s top priorities, “Determine and analyze the neural pathways by which acupuncture exerts its therapeutic effects.” Our strong preliminary data, from Dahl Salt Sensitive (DSS) HTNive rats, show that our targeted acupoints, which simultaneously activate afferents in the median, tibial, and deep peroneal nerves then modulate CNS regulation by activation of neurons in the nucleus of tractus solitarius (NTS), dorsal motor nucleus of the vagus (DMV). This modulation resulted in an increase in descending peripheral parasympathetic splenic activity. Treatment with cEA also reduced presympathetic neuronal and splanchnic sympathetic nerve activities. In this study, we will investigate if cEA treatment leads to BP reduction by improving autonomic dysfunction and decreasing inflammation through the neural mechanistic pathways we have preliminarily discovered. Our main aim is to assess mechanisms of the BP lowering effect of cEA in HTNive animals and then validate the improvement in autonomic indices by translating it in mild-moderative HTNive patients. We plan to achieve this by: 1) direct assessment of the effect of cEA on neurons in the hypothalamic and brainstem regions controlling sympathetic and parasympathetic balance including NTS, DMV, paraventricular nucleus, and rostral ventrolateral medulla, as well as sympathetic and parasympathetic efferent activities; 2) investigating if cEA reduces inflammation through acetylcholinergic receptors (AChR) activity in DSS HTNive rats; and 3) using a parallel 2x2 factorial design in a human randomized control study, primarily assess effects of cEA compared to sham-EA (as well as secondarily compare sympathoinhibitory-EA, anti-inflammatory-EA, and cEA) on physiological alterations in autonomic function and secondarily on chronic inflammation. If successful, this study would address the mechanistic basis for the effects of EA as a therapeutic option for HTNive patients who are not at optimal BP goals with conventional therapy alone.
项目总结

项目成果

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Shaista Malik其他文献

Shaista Malik的其他文献

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{{ truncateString('Shaista Malik', 18)}}的其他基金

Neuroimmune mechanisms underlying electroacupuncture effect on vascular function
电针影响血管功能的神经免疫机制
  • 批准号:
    10470285
  • 财政年份:
    2021
  • 资助金额:
    $ 67.99万
  • 项目类别:
Neuroimmune mechanisms underlying electroacupuncture effect on vascular function
电针影响血管功能的神经免疫机制
  • 批准号:
    10693901
  • 财政年份:
    2021
  • 资助金额:
    $ 67.99万
  • 项目类别:
SBHW-PREDICT (The role of PRoteomics, gEnetics, and Directed Imaging using CT)
SBHW-PREDICT(蛋白质组学、遗传学和 CT 定向成像的作用)
  • 批准号:
    9264579
  • 财政年份:
    2015
  • 资助金额:
    $ 67.99万
  • 项目类别:
SBHW-PREDICT (The role of PRoteomics, gEnetics, and Directed Imaging using CT)
SBHW-PREDICT(蛋白质组学、遗传学和 CT 定向成像的作用)
  • 批准号:
    8946099
  • 财政年份:
    2015
  • 资助金额:
    $ 67.99万
  • 项目类别:
SBHW-PREDICT (The role of PRoteomics, gEnetics, and Directed Imaging using CT)
SBHW-PREDICT(蛋白质组学、遗传学和 CT 定向成像的作用)
  • 批准号:
    9109508
  • 财政年份:
    2015
  • 资助金额:
    $ 67.99万
  • 项目类别:
Image based cardiovascular risk communication in high risk patients with diabetes
基于图像的糖尿病高危患者心血管风险沟通
  • 批准号:
    8047712
  • 财政年份:
    2011
  • 资助金额:
    $ 67.99万
  • 项目类别:
Image based cardiovascular risk communication in high risk patients with diabetes
基于图像的糖尿病高危患者心血管风险沟通
  • 批准号:
    8213510
  • 财政年份:
    2011
  • 资助金额:
    $ 67.99万
  • 项目类别:
Image based cardiovascular risk communication in high risk patients with diabetes
基于图像的糖尿病高危患者心血管风险沟通
  • 批准号:
    8605066
  • 财政年份:
    2011
  • 资助金额:
    $ 67.99万
  • 项目类别:
Image based cardiovascular risk communication in high risk patients with diabetes
基于图像的糖尿病高危患者心血管风险沟通
  • 批准号:
    8426135
  • 财政年份:
    2011
  • 资助金额:
    $ 67.99万
  • 项目类别:
Image based cardiovascular risk communication in high risk patients with diabetes
基于图像的糖尿病高危患者心血管风险沟通
  • 批准号:
    8795750
  • 财政年份:
    2011
  • 资助金额:
    $ 67.99万
  • 项目类别:

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  • 资助金额:
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    9348587
  • 财政年份:
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针灸预防老年肌少症方法的建立
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  • 财政年份:
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  • 批准号:
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  • 财政年份:
    2014
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    Grant-in-Aid for Young Scientists (B)
A Method for Evaluating Acupuncture Therapy in Pain Management
评估针灸治疗疼痛的方法
  • 批准号:
    8518241
  • 财政年份:
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A Method for Evaluating Acupuncture Therapy in Pain Management
评估针灸治疗疼痛的方法
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  • 财政年份:
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  • 财政年份:
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  • 资助金额:
    $ 67.99万
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A Method for Evaluating Acupuncture Therapy in Pain Management
评估针灸治疗疼痛的方法
  • 批准号:
    7845141
  • 财政年份:
    2009
  • 资助金额:
    $ 67.99万
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A Method for Evaluating Acupuncture Therapy in Pain Management
评估针灸治疗疼痛的方法
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