Evaluation of the bilateral cardiac afferent distribution at the spinal and vagal ganglia by retrograde labeling

Caglar, Tuba Akgul; Durdu, Z.B.; Turhan, Mehmet Ugurcan; Günal, Mehmet Yalçın; Aydın, Mehmet; Öztürk, Gürkan; Çağavı, Esra

doi:10.1016/j.brainres.2020.147201

Cited by 9 publications

(8 citation statements)

References 39 publications

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“…Conventional dyes and tracers have the following characteristics: they tend to be nonspecific in that they label both vagal afferent and efferent neurons (Altschuler et al., 1989 ; Shapiro & Miselis, 1985 ); they exhibit variable diffusion in the target tissue (Hunter & Undem, 1999 ); they exhibit biased uptake, for example, the cholera toxin b subunit tracer preferentially labels myelinated afferents (Hermes, Colbert, & Aicher, 2014 ; Herrity, Rau, Petruska, Stirling, & Hubscher, 2014 ); and they are inefficiently transported along highly branched axons, for example, horseradish peroxidase based tracers inadequately label thin diameter axonal branches (Kubin, Kimura, & Davies, 1991 ). These factors may lead to differences in uptake of different tracers at sensory terminal endings in the same organ (Akgul Caglar et al., 2021 ; Saleeba, Dempsey, Le, Goodchild, & McMullan, 2019 ) and skew interpretations of results. Viral labeling also needs to be considered carefully with outcomes influenced by several factors, including tropism (Saleeba et al., 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Analysis of the distribution of vagal afferent projections from different peripheral organs to the nucleus of the solitary tract in rats

Bassi

Connelly

Butler

et al. 2022

J of Comparative Neurology

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Anatomical tracing studies examining the vagal system can conflate details of sensory afferent and motor efferent neurons. Here, we used a serotype of adeno-associated virus that transports retrogradely and exhibits selective tropism for vagal afferents, to map their soma location and central termination sites within the nucleus of the solitary tract (NTS). We examined the vagal sensory afferents innervating the trachea, duodenum, stomach, or heart, and in some animals, from two organs concurrently.We observed no obvious somatotopy in the somata distribution within the nodose ganglion. The central termination patterns of afferents from different organs within the NTS overlap substantially. Convergence of vagal afferent inputs from different organs onto single NTS neurons is observed. Abdominal and thoracic afferents terminate throughout the NTS, including in the rostral NTS, where the 7th cranial nerve inputs are known to synapse. To address whether the axonal labeling produced by viral transduction is so widespread because it fills axons traveling to their targets, and not just terminal fields, we labeled pre and postsynaptic elements of vagal afferents in the NTS . Vagal afferents form multiple putative synapses as they course through the NTS, with each vagal afferent neuron distributing sensory signals to multiple second-order NTS neurons. We observe little selectivity between vagal afferents from different visceral targets and NTS neurons with common neurochemical phenotypes, with afferents from different organs making close appositions with the same NTS neuron. We conclude that specific viscerosensory information is distributed widely within the NTS and that the coding of this input is probably determined by the intrinsic properties and projections of the second-order neuron.

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Section: Discussionmentioning

confidence: 99%

Analysis of the distribution of vagal afferent projections from different peripheral organs to the nucleus of the solitary tract in rats

Bassi

Connelly

Butler

et al. 2022

J of Comparative Neurology

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“…Single-site DRGS showed an effective afferent neuromodulation in the setting of pain relief (Franken et al, 2018;Piedade et al, 2019); therefore in this study, we chose to stimulate DRG at a single site at the left T2, which would also be a more clinically pragmatic approach. The T2-level selection was based on the fact that multiple cardiac afferent nerve fiber travels to thoracic spinal cords through the C6-T6 DRGs bilaterally, with the largest numbers to the T2-T4 (Hopkins and Armour, 1989), and the fact that cardiac afferents are distributed symmetrically between the left and right sides (Akgul Caglar et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Neuromodulation With Thoracic Dorsal Root Ganglion Stimulation Reduces Ventricular Arrhythmogenicity

et al. 2021

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Introduction: Sympathetic hyperactivity is strongly associated with ventricular arrhythmias and sudden cardiac death. Neuromodulation provides therapeutic options for ventricular arrhythmias by modulating cardiospinal reflexes and reducing sympathetic output at the level of the spinal cord. Dorsal root ganglion stimulation (DRGS) is a recent neuromodulatory approach; however, its role in reducing ventricular arrhythmias has not been evaluated. The aim of this study was to determine if DRGS can reduce cardiac sympathoexcitation and the indices for ventricular arrhythmogenicity induced by programmed ventricular extrastimulation. We evaluated the efficacy of thoracic DRGS at both low (20 Hz) and high (1 kHz) stimulation frequencies.Methods: Cardiac sympathoexcitation was induced in Yorkshire pigs (n = 8) with ventricular extrastimulation (S1/S2 pacing), before and after DRGS. A DRG-stimulating catheter was placed at the left T2 spinal level, and animals were randomized to receive low-frequency (20 Hz and 0.4 ms) or high-frequency (1 kHz and 0.03 ms) DRGS for 30 min. High-fidelity cardiac electrophysiological recordings were performed with an epicardial electrode array measuring the indices of ventricular arrhythmogenicity—activation recovery intervals (ARIs), electrical restitution curve (Smax), and Tpeak–Tend interval (Tp-Te interval).Results: Dorsal root ganglion stimulation, at both 20 Hz and 1 kHz, decreased S1/S2 pacing-induced ARI shortening (20 Hz DRGS −21±7 ms, Control −50±9 ms, P = 0.007; 1 kHz DRGS −13 ± 2 ms, Control −46 ± 8 ms, P = 0.001). DRGS also reduced arrhythmogenicity as measured by a decrease in Smax (20 Hz DRGS 0.5 ± 0.07, Control 0.7 ± 0.04, P = 0.006; 1 kHz DRGS 0.5 ± 0.04, Control 0.7 ± 0.03, P = 0.007), and a decrease in Tp-Te interval/QTc (20 Hz DRGS 2.7 ± 0.13, Control 3.3 ± 0.12, P = 0.001; 1 kHz DRGS 2.8 ± 0.08, Control; 3.1 ± 0.03, P = 0.007).Conclusions: In a porcine model, we show that thoracic DRGS decreased cardiac sympathoexcitation and indices associated with ventricular arrhythmogenicity during programmed ventricular extrastimulation. In addition, we demonstrate that both low-frequency and high-frequency DRGS can be effective neuromodulatory approaches for reducing cardiac excitability during sympathetic hyperactivity.

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“…Expression of Tuj-1 is primarily restricted to central and peripheral nervous system. Tuj-1 plays a critical role in proper axon guidance and maintenance, which is a pan-neuronal marker [ 26 , 27 ]. At this time point, mature neurons (labeled “NeuN”) and neural stem cells (labeled “Nanog”) were determined in the organoids ( Figure 1(d) ).…”

Section: Resultsmentioning

confidence: 99%

Human Cerebral Organoid Implantation Alleviated the Neurological Deficits of Traumatic Brain Injury in Mice

Bao

Fang

Zong

et al. 2021

Oxidative Medicine and Cellular Longevity

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Traumatic brain injury (TBI) causes a high rate of mortality and disability, and its treatment is still limited. Loss of neurons in damaged area is hardly rescued by relative molecular therapies. Based on its disease characteristics, we transplanted human embryonic stem cell- (hESC-) derived cerebral organoids in the brain lesions of controlled cortical impact- (CCI-) modeled severe combined immunodeficient (SCID) mice. Grafted organoids survived and differentiated in CCI-induced lesion pools in mouse cortical tissue. Implanted cerebral organoids differentiated into various types of neuronal cells, extended long projections, and showed spontaneous action, as indicated by electromyographic activity in the grafts. Induced vascularization and reduced glial scar were also found after organoid implantation, suggesting grafting could improve local situation and promote neural repair. More importantly, the CCI mice’s spatial learning and memory improved after organoid grafting. These findings suggest that cerebral organoid implanted in lesion sites differentiates into cortical neurons, forms long projections, and reverses deficits in spatial learning and memory, a potential therapeutic avenue for TBI.

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Evaluation of the bilateral cardiac afferent distribution at the spinal and vagal ganglia by retrograde labeling

Cited by 9 publications

References 39 publications

Analysis of the distribution of vagal afferent projections from different peripheral organs to the nucleus of the solitary tract in rats

Analysis of the distribution of vagal afferent projections from different peripheral organs to the nucleus of the solitary tract in rats

Neuromodulation With Thoracic Dorsal Root Ganglion Stimulation Reduces Ventricular Arrhythmogenicity

Human Cerebral Organoid Implantation Alleviated the Neurological Deficits of Traumatic Brain Injury in Mice

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