The superior cervical ganglia modulate ventilatory responses to hypoxia independently of pre-ganglionic drive from the cervical sympathetic chain

Superior cervical ganglia (SCG) post-ganglionic neurons receive pre-ganglionic drive via the cervical sympathetic chain (CSC). The SCG projects to structures like the carotid bodies (e.g., vasculature, chemosensitive glomus cells), upper airway (e.g., tongue, nasopharynx) and to parenchyma and cerebral arteries throughout the brain. We previously reported that a hypoxic gas challenge elicited an array of ventilatory responses in sham-operated (SHAM) freely-moving adult male C57BL6 mice and that responses were altered in mice with bilateral transection of the cervical sympathetic chain (CSCX). Since the CSC provides pre-ganglionic innervation to the SCG, we presumed that mice with superior cervical ganglionectomy (SCGX) would respond similarly to hypoxic gas challenge as CSCX mice. However, while SCGX mice had altered responses during hypoxic gas challenge that occurred in CSCX mice (e.g., more rapid occurrence of changes in frequency of breathing and minute ventilation), SCGX mice displayed numerous responses to hypoxic gas challenge that CSCX mice did not, including reduced total increases in frequency of breathing, minute ventilation, inspiratory and expiratory drives, peak inspiratory and expiratory flows, and appearance of non-eupneic breaths. In conclusion, hypoxic gas challenge may directly activate sub-populations of SCG cells, including sub-populations of post-ganglionic neurons and small intensely fluorescent (SIF) cells, independently of CSC drive, and that SCG drive to these structures dampens the initial occurrence of the hypoxic ventilatory response, while promoting the overall magnitude of the response. The multiple effects of SCGX may be due to loss of innervation to peripheral and central structures with differential roles in breathing control.

Peripheral nerve blocks in the cervical region: from anatomy to ultrasound-guided techniques

Cervical plexus nerve blocks have been employed in various head and neck operations. Both adequate anaesthesia and analgesia are attained in clinical practice. Nowadays, ultrasound imaging in regional anaesthesia is driven towards a certain objective that dictates high accuracy and safety during the implementation of peripheral nerve blocks. In the cervical region, ultrasound-guided nerve blocks have routinely been conducted only for the past few years and thus only a small number of publications pervade the current literature. Moreover, the sonoanatomy of the neck, the foundation stone of interventional techniques, is very challenging; multiple muscles and fascial layers compose a complex of compartments in a narrow anatomic region, in which local anaesthetics are injected. Therefore, this review intends to deliver new insights into ultrasound-guided peripheral nerve block techniques in the neck. The sonoanatomy of the cervical region, in addition to the cervical plexus, cervical ganglia, superior and recurrent laryngeal nerve blocks are comprehensively discussed.

Manipulation based on Fryette’s Laws increases heart rate variability and muscle flexibility in subjects with headache

Background: The sympathetic nervous system has a direct connection with the cervical spine, through the cervical ganglia, in the superior cervical ganglion; therefore the manipulation of the superior cervical spine could result on modifications of the heart rate variability (HRV). Objective: To evaluate the immediate effect of the manipulation based on the Fryette’s laws of the superior cervical spinal (SCS) on HRV and posterior chain flexibility (PCF) in subjects with headache. Methods/Design: Twelve volunteers of both genders (23.8 ± 2.8 years), who had complaints of headache, participated in the study. Before and immediately after the HRV assessment, PCF was measured with the assistance of Wells and Dillon’s Bench test. For this the volunteer remained seated with the spine erect, lower limbs extended and feet resting on the bench. Then it was requested maximum flexion of the trunk and measured with a ruler the achieved distance. The HRV was obtained by the cardiofrequencymeter Polar RS800cx and captured for continuous fifteen minutes with the volunteer resting in supine position. At five minutes of collection, with the volunteer in the same position, the SCS manipulation technique (Fryette’s Laws) was performed bilaterally. The HRV assessment was performed in the time domain by the RMSSD index of RR intervals (Matlab For Windows version 6.1) in two different moments: before and after the manipulation. Statistical analysis consisted of the Kolmogorov-Smirnov test and paired t-test for comparison of pre and post manipulation variables (p<0.05). Results: There was a significant increase (p = 0.004) in the RMSSD index after the manipulation (from 42.58 ± 24.52 ms before the manipulation to 51.25 ± 27.55 ms ten minutes after manipulation). The PCF also increased significantly (p = 0.03) after the SCS manipulation (from 17.65 ± 11.9 cm to 21.40 ± 13.8 cm). Conclusions: The manipulation of SCS increased the HRV through the increase of the RMSSD index indicating a predominance of parasympathetic activity, and improved the PCF of the studied volunteers, also reduced signs and symptoms of headache.

Vagosympathetic imbalance induced thyroiditis following subarachnoid hemorrhage: a preliminary study

Introduction: This preliminary study evaluates the possible responsibility of ischemia-induced vagosympathetic imbalances following subarachnoid hemorrhage (SAH), for the onset of autoimmune thyroiditis. Methods: Twenty-two rabbits were chosen from our former experimental animals, five of which were picked from healthy rabbits as control (nG-I=5). Sham group (nG-II=5) and animals with thyroid pathologies (nG-III=12) were also included after a one-month-long experimental SAH follow-up. Thyroid hormone levels were measured weekly, and animals were decapitated. Thyroid glands, superior cervical ganglia, and intracranial parts of vagal nerve sections obtained from our tissue archives were reexamined with routine/immunohistochemical methods. Thyroid hormone levels, hormone-filled total follicle volumes (TFVs) per cubic millimeter, degenerated neuron density (DND) of vagal nuclei and neuron density of superior cervical ganglia were measured and statistically compared. Results: The mean neuron density of both superior cervical ganglia was estimated as 8230±983/ mm3 in study group animals with severe thyroiditis, 7496±787/mm3 in the sham group and 6416±510/mm3 in animals with normal thyroid glands. In control group (group I), T3 was 107±11 μg/dL, T4: 1,43±0.32 μg/dL and TSH <0.5, while mean TFV was 43%/mm3 and DND of vagal nuclei was 3±1/mm3. In sham group (group II), T3 was 96±11 μg/dL, T4: 1.21±0.9 μg/ dL and TSH>0.5 while TFV was 38%/mm3 and DND of vagal nuclei was 13±4. In study group, T3 was 54±8 μg/dL, T4: 1,07±0.3 μg/dL and TSH >0.5, while TFV was 27%/mm3 and DND of vagal nuclei was 42±9/mm3. Conclusion: Sympathovagal imbalance characterized by relative sympathetic hyperactivity based on vagal insufficiency should be considered as a new causative agent for hypothyroidism.

Reperfusion Arrhythmias Increase after Superior Cervical Ganglionectomy Due to Conduction Disorders and Changes in Repolarization

Pharmacological concentrations of melatonin reduce reperfusion arrhythmias, but less is known about the antiarrhythmic protection of the physiological circadian rhythm of melatonin. Bilateral surgical removal of the superior cervical ganglia irreversibly suppresses melatonin rhythmicity. This study aimed to analyze the cardiac electrophysiological effects of the loss of melatonin circadian oscillation and the role played by myocardial melatonin membrane receptors, SERCA2A, TNFα, nitrotyrosine, TGFβ, KATP channels, and connexin 43. Three weeks after bilateral removal of the superior cervical ganglia or sham surgery, the hearts were isolated and submitted to ten minutes of regional ischemia followed by ten minutes of reperfusion. Arrhythmias, mainly ventricular tachycardia, increased during reperfusion in the ganglionectomy group. These hearts also suffered an epicardial electrical activation delay that increased during ischemia, action potential alternants, triggered activity, and dispersion of action potential duration. Hearts from ganglionectomized rats showed a reduction of the cardioprotective MT2 receptors, the MT1 receptors, and SERCA2A. Markers of nitroxidative stress (nitrotyrosine), inflammation (TNFα), and fibrosis (TGFβ and vimentin) did not change between groups. Connexin 43 lateralization and the pore-forming subunit (Kir6.1) of KATP channels increased in the experimental group. We conclude that the loss of the circadian rhythm of melatonin predisposes the heart to suffer cardiac arrhythmias, mainly ventricular tachycardia, due to conduction disorders and changes in repolarization.

Inhibition of vascular adventitial remodeling by netrin-1 in diabetic rats

Cardiovascular complications of type 2 diabetes mellitus (T2DM) are associated with vascular remodeling in the arteries. Perivascular sympathetic neurons release an abundance of trophic factors to regulate vascular function via a paracrine signaling. Netrin-1, a diffusible protein that can be secreted outside the cell, is one of common signals of ‘conversation’ between nerve and vessel. The present study investigated whether netrin-1 is a novel modulator of sympathetic neurons paracrine signaling and played a critical role in vascular adventitial remodeling under T2DM. Vascular adventitial remodeling was observed in adventitial fibroblasts (AFs) responding to netrin-1 deficiency in the supernatant from primary rat superior cervical ganglia (SCG) neurons, shown as AFs proliferation, migration, and collagen deposition. Conditioned medium from the high glucose (HG)-treated SCG neurons contributed to AFs remodeling, which was effectively alleviated by exogenous netrin-1 supplementation. Further, it was found that uncoordinated-5-B (Unc5b) was mainly expressed in AFs among netrin-1 specific receptors. Treatment of netrin-1 inhibited H2O2 production derived from NADPH oxidase 4 (NOX4) through the UNC5b/CAMP/PKA signal pathway in AFs remodeling. In vivo, aorta adventitial remodeling was accompanied with the downregulation of netrin-1 in the perivascular sympathetic nerve in T2DM rats. Such abnormalities were restored by netrin-1 intervention, which was associated with the inhibition of NOX4 expression in the aorta adventitia. In conclusion, netrin-1 is a novel modulator of sympathetic neurons paracrine signaling to maintain AFs function. Vascular adventitial remodeling was aggravated by sympathetic neurons paracrine signaling under hyperglycemia, which was ameliorated by netrin-1 treatment through the UNC5b/CAMP/PKA/NOX4 pathway.