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Science Translational Medicine Oct 2023To date, there are no approved treatments for the diminished strength and paralysis that result from the loss of peripheral nerve function due to trauma, heritable...
To date, there are no approved treatments for the diminished strength and paralysis that result from the loss of peripheral nerve function due to trauma, heritable neuromuscular diseases, or aging. Here, we showed that denervation resulting from transection of the sciatic nerve triggered a marked increase in the prostaglandin-degrading enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in skeletal muscle in mice, providing evidence that injury drives early expression of this aging-associated enzyme or gerozyme. Treating mice with a small-molecule inhibitor of 15-PGDH promoted regeneration of motor axons and formation of neuromuscular synapses leading to an acceleration in recovery of force after an acute nerve crush injury. In aged mice with chronic denervation of muscles, treatment with the 15-PGDH inhibitor increased motor neuron viability and restored neuromuscular junctions and function. These presynaptic changes synergized with previously reported muscle tissue remodeling to result in a marked increase in the strength of aged muscles. We further found that 15-PGDH aggregates defined the target fibers that are histopathologic hallmarks of human neurogenic myopathies, suggesting that the gerozyme may be involved in their etiology. Our data suggest that inhibition of 15-PGDH may constitute a therapeutic strategy to physiologically boost prostaglandin E2, restore neuromuscular connectivity, and promote recovery of strength after acute or chronic denervation due to injury, disease, or aging.
Topics: Mice; Animals; Humans; Aged; Synapses; Hydroxyprostaglandin Dehydrogenases; Prostaglandins; Muscle, Skeletal; Denervation; Nerve Regeneration
PubMed: 37820010
DOI: 10.1126/scitranslmed.adg1485 -
Hypertension Research : Official... Feb 2022Renal nerves have critical roles in regulating blood pressure and fluid volume, and their dysfunction is closely related with cardiovascular diseases. Renal nerves are... (Review)
Review
Renal nerves have critical roles in regulating blood pressure and fluid volume, and their dysfunction is closely related with cardiovascular diseases. Renal nerves are composed of sympathetic efferent and sensory afferent nerves. Activation of the efferent renal sympathetic nerves induces renin secretion, sodium absorption, and increased renal vascular resistance, which lead to increased blood pressure and fluid retention. Afferent renal sensory nerves, which are densely innervated in the renal pelvic wall, project to the hypothalamic paraventricular nucleus in the brain to modulate sympathetic outflow to the periphery, including the heart, kidneys, and arterioles. The effects of renal denervation on the cardiovascular system are mediated by both efferent denervation and afferent denervation. The first half of this review focuses on basic research using animal models of hypertension and heart failure, and addresses the therapeutic effects of renal denervation for hypertension and heart failure, including underlying mechanisms. The second half of this review focuses on clinical research related to catheter-based renal denervation in patients with hypertension. Randomized sham-controlled trials using second-generation devices, endovascular radiofrequency-based devices and ultrasound-based devices are reviewed and their results are assessed. This review summarizes the basic and clinical evidence of renal denervation to date, and discusses future prospects and potential developments in renal denervation therapy for cardiovascular diseases.
Topics: Animals; Blood Pressure; Denervation; Humans; Hypertension; Kidney; Sympathectomy; Sympathetic Nervous System
PubMed: 34921299
DOI: 10.1038/s41440-021-00827-7 -
International Journal of Molecular... Jul 2022This Special Issue presents some of the most recent studies on the skeletal muscle denervation [...].
This Special Issue presents some of the most recent studies on the skeletal muscle denervation [...].
Topics: Humans; Muscle Denervation; Muscle, Skeletal; Muscular Atrophy
PubMed: 35886838
DOI: 10.3390/ijms23147489 -
Circulation Research Apr 2021In the past decade, efforts to improve blood pressure control have looked beyond conventional approaches of lifestyle modification and drug therapy to embrace... (Review)
Review
In the past decade, efforts to improve blood pressure control have looked beyond conventional approaches of lifestyle modification and drug therapy to embrace interventional therapies. Based upon animal and human studies clearly demonstrating a key role for the sympathetic nervous system in the etiology of hypertension, the newer technologies that have emerged are predominantly aimed at neuromodulation of peripheral nervous system targets. These include renal denervation, baroreflex activation therapy, endovascular baroreflex amplification therapy, carotid body ablation, and pacemaker-mediated programmable hypertension control. Of these, renal denervation is the most mature, and with a recent series of proof-of-concept trials demonstrating the safety and efficacy of radiofrequency and more recently ultrasound-based renal denervation, this technology is poised to become available as a viable treatment option for hypertension in the foreseeable future. With regard to baroreflex activation therapy, endovascular baroreflex amplification, carotid body ablation, and programmable hypertension control, these are developing technologies for which more human data are required. Importantly, central nervous system control of the circulation remains a poorly understood yet vital component of the hypertension pathway and mandates further investigation. Technology to improve blood pressure control through deep brain stimulation of key cardiovascular control territories is, therefore, of interest. Furthermore, alternative nonsympathomodulatory intervention targeting the hemodynamics of the circulation may also be worth exploring for patients in whom sympathetic drive is less relevant to hypertension perpetuation. Herein, we review the aforementioned technologies with an emphasis on the preclinical data that underpin their rationale and the human evidence that supports their use.
Topics: Animals; Arteriovenous Shunt, Surgical; Baroreflex; Blood Pressure; Carotid Body; Deep Brain Stimulation; Denervation; Humans; Hypertension; Kidney; Pacemaker, Artificial; Sympathetic Nervous System; Transcutaneous Electric Nerve Stimulation
PubMed: 33793330
DOI: 10.1161/CIRCRESAHA.121.318091 -
Physical Medicine and Rehabilitation... Nov 2021Radiofrequency ablation (RFA) is still an emergent technique for the management of chronic hip pain. Although the ablation technique for facet articular branches of... (Review)
Review
Radiofrequency ablation (RFA) is still an emergent technique for the management of chronic hip pain. Although the ablation technique for facet articular branches of lumbar and cervical spine was already established, the literature on the targets and technique of needle placement for hip denervation are evolving. This article summarizes the current understanding of the anatomy of the articular branches, sonoanatomy, and the suggested techniques for the RFA of the hip. It also reviews the literature on the clinical studies.
Topics: Ablation Techniques; Catheter Ablation; Denervation; Humans
PubMed: 34593141
DOI: 10.1016/j.pmr.2021.05.010 -
The American Journal of Medicine Sep 2023Renal denervation is not a cure for hypertension. Although more recent sham-controlled trials were positive, a significant minority of patients in each trial were...
Renal denervation is not a cure for hypertension. Although more recent sham-controlled trials were positive, a significant minority of patients in each trial were unresponsive. The optimal patient or patients need to be defined. Combined systolic/diastolic hypertension appears more responsive than isolated systolic hypertension. It remains uncertain whether patients with comorbidities associated with higher adrenergic tone should be targeted, including obesity, diabetes, sleep apnea, and chronic kidney disease. No biomarker can adequately predict response. A key to a successful response is the adequacy of denervation, which currently cannot be assessed in real time. It is uncertain what is the optimal denervation methodology: radiofrequency, ultrasound, or ethanol injection. Radiofrequency requires targeting the distal main renal artery plus major branches and accessory arteries. Although denervation appears to be safe, conclusive data on quality of life, improved target organ damage, and reduced cardiovascular events/mortality are required before denervation can be generally recommended.
Topics: Humans; Hypertension; Kidney; Quality of Life; Treatment Outcome; Denervation
PubMed: 37230403
DOI: 10.1016/j.amjmed.2023.05.010 -
Urology Feb 2020
Topics: Denervation; Female; Humans; Urinary Bladder, Overactive
PubMed: 32033686
DOI: 10.1016/j.urology.2019.08.064 -
Journal of the American College of... Nov 2022
Topics: Humans; Kidney; Sympathectomy; Hypertension; Denervation; Blood Pressure; Antihypertensive Agents
PubMed: 36357088
DOI: 10.1016/j.jacc.2022.09.025 -
Annual Review of Physiology Feb 2021Heart failure (HF) is a global pandemic with a poor prognosis after hospitalization. Despite HF syndrome complexities, evidence of significant sympathetic overactivity... (Review)
Review
Heart failure (HF) is a global pandemic with a poor prognosis after hospitalization. Despite HF syndrome complexities, evidence of significant sympathetic overactivity in the manifestation and progression of HF is universally accepted. Confirmation of this dogma is observed in guideline-directed use of neurohormonal pharmacotherapies as a standard of care in HF. Despite reductions in morbidity and mortality, a growing patient population is resistant to these medications, while off-target side effects lead to dismal patient adherence to lifelong drug regimens. Novel therapeutic strategies, devoid of these limitations, are necessary to attenuate the progression of HF pathophysiology while continuing to reduce morbidity and mortality. Renal denervation is an endovascular procedure, whereby the ablation of renal nerves results in reduced renal afferent and efferent sympathetic nerve activity in the kidney and globally. In this review, we discuss the current state of preclinical and clinical research related to renal sympathetic denervation to treat HF.
Topics: Animals; Disease Progression; Heart Failure; Humans; Kidney; Sympathectomy
PubMed: 33074771
DOI: 10.1146/annurev-physiol-031620-093431 -
European Heart Journal Apr 2023Since the publication of the 2018 European Society of Cardiology/European Society of Hypertension (ESC/ESH) Guidelines for the Management of Arterial Hypertension,...
Renal denervation in the management of hypertension in adults. A clinical consensus statement of the ESC Council on Hypertension and the European Association of Percutaneous Cardiovascular Interventions (EAPCI).
Since the publication of the 2018 European Society of Cardiology/European Society of Hypertension (ESC/ESH) Guidelines for the Management of Arterial Hypertension, several high-quality studies, including randomised, sham-controlled trials on catheter-based renal denervation (RDN) were published, confirming both the blood pressure (BP)-lowering efficacy and safety of radiofrequency and ultrasound RDN in a broad range of patients with hypertension, including resistant hypertension. A clinical consensus document by the ESC Council on Hypertension and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) on RDN in the management of hypertension was considered necessary to inform clinical practice. This expert group proposes that RDN is an adjunct treatment option in uncontrolled resistant hypertension, confirmed by ambulatory BP measurements, despite best efforts at lifestyle and pharmacological interventions. RDN may also be used in patients who are unable to tolerate antihypertensive medications in the long term. A shared decision-making process is a key feature and preferably includes a patient who is well informed on the benefits and limitations of the procedure. The decision-making process should take (i) the patient's global cardiovascular (CV) risk and/or (ii) the presence of hypertension-mediated organ damage or CV complications into account. Multidisciplinary hypertension teams involving hypertension experts and interventionalists evaluate the indication and facilitate the RDN procedure. Interventionalists require expertise in renal interventions and specific training in RDN procedures. Centres performing these procedures require the skills and resources to deal with potential complications. Future research is needed to address open questions and investigate the impact of BP-lowering with RDN on clinical outcomes and potential clinical indications beyond hypertension.
Topics: Humans; Adult; Renal Artery; Hypertension; Kidney; Blood Pressure; Antihypertensive Agents; Denervation; Treatment Outcome; Sympathectomy
PubMed: 36790101
DOI: 10.1093/eurheartj/ehad054