Background: We previously showed that administration of an Endocannabinoid receptor-1 (CB1) inverse agonist (Rimonabant) induced an increase in splanchnic nerve activity, and "browning" of mesenteric ...fat. Furthermore, we demonstrated that selective splanchnic denervation significantly reduces the response to Rimonabant, specifically on food intake. Hypothesis: we examined if the sensory/spinal branch of the splanchnic nerve mediates the effect on energy balance and food intake. Methods: (1) We explored the localization of peripheral CB1 within the sensory nerve endings of the luminal gut and the effects of CB1-inverse agonist in mouse models of spinal afferent denervation on two obesogenic diets. (2) we also explored whether gastric bypassinduced changes in gut microbiome mediate its energy regulating effects through CB1 -signaling via the spinal/sensory pathway. Results: We found that intestinal CB1 co-localizes mainly with CGRPexpressing cells (sensory neurons) and not epithelial, enteroendocrine, or any immune cell. We found more significant co-localization of CB1 to the sensory/spinal fibers (celiac ganglion and DRG) than vagal sensory fibers (nodose ganglion). Then, using a model of selective afferent splanchnic denervation we found that the effects of Rimonabant were attenuated only in denervated high-fat diet and not high-carb diet induced obese mice. Finally, transferring fecal material from RYGB and Sham -operated mice into naïf recipients induces a significant increase in afferent and efferent splanchnic nerve activity of RYGB-stool recipients compared to their controls. Finally, intestinal CB1 expression was significantly lower in RYGB-stool recipients compared to their controls. Conclusions: Gut microbiome communicate energy signals from the gut to the brain through sensory/spinal afferent neurons via a CB1-depenedent pathway.
Thumb carpometacarpal osteoarthritis (CMCJ OA) is a common problem. Joint denervation presents a number of theoretical advantages over more traditional surgical options; it is minimally invasive, it ...does not require a prosthesis or postoperative immobilisation, and does not preclude future surgery. It can be of particular benefit in patients who require good range of motion which other forms of surgery may compromise. Despite these potential advantages, selective denervation of the thumb CMCJ is not considered as part of the routine surgical armamentarium for the treatment of thumb base OA. The purpose of this study is to analyse the evidence for thumb CMCJ denervation; evaluating patient selection, surgical techniques, complications and outcomes. A systematic review was performed on all published literature relating to thumb CMCJ denervation. Nine studies were identified with 184 denervation procedures undertaken in 175 patients. The length of follow-up was available in eight studies (mean 36.5 months range 6–152 months). All authors reported improvement in pain and seven studies reported improvement in function. Eleven patients in total suffered persistent joint pain, ten of which proceeded to trapeziectomy and one patient underwent a revision denervation to address potentially missed dorsal sensory branches. The overall complication rate was 11.4% (0–27.5%) consisting of minor complications. This review highlights the paucity of high-quality data and the requirement for a multi-centre, randomised study with validated outcome measures to further define the role of denervation in the management of thumb base OA.
Hypertension is a primary contributor to cardiovascular disease, and the leading risk factor for loss of quality adjusted life years. Up to 50% of the cases of hypertension in the US remain ...uncontrolled. Additionally, 8-18% of the hypertensive population have resistant hypertension, uncontrolled pressure despite three different anti-hypertensive agents. Recently, catheter-based, percutaneous renal denervation emerged as a method for ablating renal sympathetic nerves for difficult to control hypertension. Initial randomized (non-sham) trials and registry analyses showed impressive benefit, but the first sham-controlled randomized controlled trial (RCT) using monopolar radiofrequency ablation showed limited benefit. With refinement of techniques to include multipolar radiofrequency, ultrasound denervation, and direct ethanol injection, RCTs demonstrated significant blood pressure improvement, leading to FDA approval of radiofrequency and ultrasound-based denervation technologies. In this review article, we summarize the major randomized sham-controlled trials and societal guidelines regarding the efficacy and safety of renal artery denervation for the treatment of uncontrolled hypertension.
Three recent renal denervation studies in both drug-naïve and drug-treated hypertensive patients demonstrated a significant reduction of ambulatory blood pressure compared with respective sham ...control groups. Improved trial design, selection of relevant patient cohorts, and optimized interventional procedures have likely contributed to these positive findings. However, substantial variability in the blood pressure response to renal denervation can still be observed and remains a challenging and important problem. The International Sympathetic Nervous System Summit was convened to bring together experts in both experimental and clinical medicine to discuss the current evidence base, novel developments in our understanding of neural interplay, procedural aspects, monitoring of technical success, and others. Identification of relevant trends in the field and initiation of tailored and combined experimental and clinical research efforts will help to address remaining questions and provide much-needed evidence to guide clinical use of renal denervation for hypertension treatment and other potential indications.
Deutschland gehört weltweit zu den Ländern, in denen die renale Denervation bei arterieller Hypertonie am energischsten vorangetrieben wird. Umso kräftiger sollte das Erdbeben sein, nachdem im Januar ...2014 bekannt wurde, dass die bisher größte randomisierte Studie zu diesem Verfahren ihren primären Wirksamkeitsendpunkt verfehlt hat. Wie geht es nun weiter?
Cover Image, Volume 49, Issue 4 Alhindi, Abrar; Shand, Megan; Smith, Hannah L. ...
Neuropathology and applied neurobiology,
August 2023, 2023-08-00, 20230801, Letnik:
49, Številka:
4
Journal Article
Recenzirano
Odprti dostop
The cover image is based on the Original Article Neuromuscular junction denervation and terminal Schwann cell loss in the hTDP‐43 overexpression mouse model of amyotrophic lateral sclerosis by Abrar ...Alhindi et al., https://doi.org/10.1111/nan.12925. Image Credit: Abrar Alhindi and Helena Chaytow.
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