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Autonomic Neuroscience : Basic &... Sep 2020Cardiac sympathetic blockade is a therapeutic approach for arrhythmias and heart failure and may be a beneficial effect of high thoracic epidural anesthesia. These... (Review)
Review
BACKGROUND
Cardiac sympathetic blockade is a therapeutic approach for arrhythmias and heart failure and may be a beneficial effect of high thoracic epidural anesthesia. These treatments require detailed knowledge of the spatial location and distribution of cardiac autonomic nerves, however, there are controversies on this subject in humans.
OBJECTIVE
To provide a systematic overview of current knowledge on human anatomy of the cardiac autonomic nervous system.
RESULTS
In contrast to the often claimed assumption that human preganglionic sympathetic cardiac neurons originate mainly from thoracic spinal segments T1-T4 or T5, there is ample evidence indicating involvement of cervical spinal segment C8 and thoracic spinal segments below T5. Whether cervical ganglia besides the stellate ganglion play a role in transmission of cardiac sympathetic signals is unclear. Similarly, there is debate on the origin of cardiac nerves from different thoracic ganglia. Most human studies report thoracic cardiac nerves emerging from the first to fourth thoracic paravertebral ganglia; others report contributions from the fifth, sixth and even the seventh thoracic ganglia. There is no agreement on the precise composition of nerve plexuses at the cardiac level. After years of debate, it is generally accepted that the vagal nerve contributes to ventricular innervation. Vagal distribution appears higher in atria, whereas adrenergic fibers exceed the number of vagal fibers in the ventricles.
CONCLUSION
Anatomy of the human cardiac autonomic nervous system is highly variable and likely extends beyond generally assumed boundaries. This information is relevant for thoracic epidural anesthesia and procedures targeting neuronal modulation of cardiac sympathetic innervation.
Topics: Adult; Animals; Autonomic Nervous System; Ganglia, Sympathetic; Heart; Humans
PubMed: 32497872
DOI: 10.1016/j.autneu.2020.102674 -
Nature Reviews. Gastroenterology &... Jun 2020The gastrointestinal tract is the only internal organ to have evolved with its own independent nervous system, known as the enteric nervous system (ENS). This Review... (Review)
Review
The gastrointestinal tract is the only internal organ to have evolved with its own independent nervous system, known as the enteric nervous system (ENS). This Review provides an update on advances that have been made in our understanding of how neurons within the ENS coordinate sensory and motor functions. Understanding this function is critical for determining how deficits in neurogenic motor patterns arise. Knowledge of how distension or chemical stimulation of the bowel evokes sensory responses in the ENS and central nervous system have progressed, including critical elements that underlie the mechanotransduction of distension-evoked colonic peristalsis. Contrary to original thought, evidence suggests that mucosal serotonin is not required for peristalsis or colonic migrating motor complexes, although it can modulate their characteristics. Chemosensory stimuli applied to the lumen can release substances from enteroendocrine cells, which could subsequently modulate ENS activity. Advances have been made in optogenetic technologies, such that specific neurochemical classes of enteric neurons can be stimulated. A major focus of this Review will be the latest advances in our understanding of how intrinsic sensory neurons in the ENS detect and respond to sensory stimuli and how these mechanisms differ from extrinsic sensory nerve endings in the gut that underlie the gut-brain axis.
Topics: Afferent Pathways; Autonomic Fibers, Preganglionic; Efferent Pathways; Enteric Nervous System; Enteroendocrine Cells; Gastrointestinal Motility; Humans; Mechanotransduction, Cellular; Myoelectric Complex, Migrating; Neural Pathways; Neurons; Neurotransmitter Agents; Sensation; Sensory Receptor Cells; Serotonin
PubMed: 32152479
DOI: 10.1038/s41575-020-0271-2 -
Chest Mar 2020
Topics: Administration, Inhalation; Amygdala; Animals; Arrhythmias, Cardiac; Autonomic Fibers, Preganglionic; Electronic Nicotine Delivery Systems; Humans; Medulla Oblongata; Nicotine; Nicotinic Agonists; Receptors, Nicotinic; Respiratory Center; Respiratory Insufficiency; Seizures; Vaping; alpha7 Nicotinic Acetylcholine Receptor
PubMed: 32145810
DOI: 10.1016/j.chest.2019.10.008 -
American Journal of Physiology. Heart... Apr 2020Inherent and acquired factors determine the integrated autonomic response to cardiovascular stressors. Excessive sympathoexcitation to ischemic stress is a major...
Inherent and acquired factors determine the integrated autonomic response to cardiovascular stressors. Excessive sympathoexcitation to ischemic stress is a major contributor to the potential for sudden cardiac death. To define fundamental aspects of cardiac-related autonomic neural network interactions within the thoracic cord, specifically as related to modulating sympathetic preganglionic (SPN) neural activity. Adult, anesthetized Yorkshire pigs ( = 10) were implanted with penetrating high-density microarrays (64 electrodes) at the T2 level of the thoracic spinal cord to record extracellular potentials concurrently from left-sided dorsal horn (DH) and SPN neurons. Electrical stimulation of the T2 paravertebral chain allowed for antidromic identification of SPNs located in the intermediolateral cell column (57 of total 1,760 recorded neurons). Cardiac stressors included epicardial touch, occlusion of great vessels to transiently alter preload/afterload, and transient occlusion of the left anterior descending coronary artery (LAD). Spatial/temporal assessment of network interactions was characterized by cross-correlation analysis. While some DH neurons responded solely to changes in preload/afterload (8.5 ± 1.9%) or ischemic stress (10.5 ± 3.9%), the majority of cardiovascular-related DH neurons were multimodal (30.2 ± 4.7%) with ischemia sensitivity being one of the modalities (26.1 ± 4.7%). The sympathoexcitation associated with transient LAD occlusion was associated with increased correlations from baseline within DH neurons (2.43 ± 0.61 to 7.30 ± 1.84%, = 0.04) and between SPN to DH neurons (1.32 ± 0.78 to 7.24 ± 1.84%, = 0.02). DH to SPN network correlations were reduced during great vessel occlusion. In conclusion, increased intrasegmental network coherence within the thoracic spinal cord contributes to myocardial ischemia-induced sympathoexcitation. In an in vivo pig model, we demonstrate using novel high-resolution neural electrode arrays that increased intrasegmental network coherence within the thoracic spinal cord contributes to myocardial ischemia-induced sympathoexcitation.
Topics: Animals; Autonomic Fibers, Preganglionic; Female; Heart; Male; Nerve Net; Spinal Cord Dorsal Horn; Stress, Physiological; Swine; Sympathetic Nervous System
PubMed: 32108524
DOI: 10.1152/ajpheart.00635.2019 -
Neurosurgery Sep 2020Preganglionic cervical root transection (PCRT) is the most severe type of brachial plexus injury. In some cases, surgical procedures must be postponed for ≥3 wk until...
BACKGROUND
Preganglionic cervical root transection (PCRT) is the most severe type of brachial plexus injury. In some cases, surgical procedures must be postponed for ≥3 wk until electromyographic confirmation. However, research works have previously shown that treating PCRT after a 3-wk delay fails to result in functional recovery.
OBJECTIVE
To assess whether the immunosuppressive drug sirolimus, by promoting neuroprotection in the acute phase of PCRT, could enable functional recovery in cases of delayed repair.
METHODS
First, rats received a left 6th to 8th cervical root transection, after which half were administered sirolimus for 1 wk. Markers of microglia, astrocytes, neurons, and autophagy were assessed at days 7 and 21. Second, animals with the same injury received nerve grafts, along with acidic fibroblast growth factor and fibrin glue, 3 wk postinjury. Sirolimus was administered to half of them for the first week. Mechanical sensation, grasping power, spinal cord morphology, functional neuron survival, nerve fiber regeneration, and somatosensory-evoked potentials (SSEPs) were assessed 1 and 23 wk postinjury.
RESULTS
Sirolimus was shown to attenuate microglial and astrocytic proliferation and enhance neuronal autophagy and survival; only rats treated with sirolimus underwent significant sensory and motor function recovery. In addition, rats who achieved functional recovery were shown to have abundant nerve fibers and neurons in the dorsal root entry zone, dorsal root ganglion, and ventral horn, as well as to have SSEPs reappearance.
CONCLUSION
Sirolimus-induced neuroprotection in the acute stage of PCRT enables functional recovery, even if surgical repair is performed after a 3-wk delay.
Topics: Animals; Axotomy; Brachial Plexus; Brachial Plexus Neuropathies; Female; Immunosuppressive Agents; Nerve Regeneration; Neuroprotection; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Recovery of Function; Sirolimus; Spinal Nerve Roots
PubMed: 31960049
DOI: 10.1093/neuros/nyz572 -
Frontiers in Cellular Neuroscience 2019Traumatic spinal cord injury (SCI) leads to disruption of sensory, motor and autonomic function, and triggers structural, physiological and biochemical changes that...
Traumatic spinal cord injury (SCI) leads to disruption of sensory, motor and autonomic function, and triggers structural, physiological and biochemical changes that cause reorganization of existing circuits that affect functional recovery. Propriospinal neurons (PN) appear to be very plastic within the inhibitory microenvironment of the injured spinal cord by forming compensatory circuits that aid in relaying information across the lesion site and, thus, are being investigated for their potential to promote locomotor recovery after experimental SCI. Yet the role of PN plasticity in autonomic dysfunction is not well characterized, notably, the disruption of supraspinal modulatory signals to spinal sympathetic neurons after SCI at the sixth thoracic spinal segment or above resulting in autonomic dysreflexia (AD). This condition is characterized by unmodulated sympathetic reflexes triggering sporadic hypertension associated with baroreflex mediated bradycardia in response to noxious yet unperceived stimuli below the injury to reduce blood pressure. AD is frequently triggered by pelvic visceral distension (bowel and bladder), and there are documented structural relationships between injury-induced sprouting of pelvic visceral afferent C-fibers. Their excitation of lumbosacral PN, in turn, sprout and relay noxious visceral sensory stimuli to rostral disinhibited thoracic sympathetic preganglionic neurons (SPN) that manifest hypertension. Herein, we review evidence for maladaptive plasticity of PN in neural circuits mediating heightened sympathetic reflexes after complete high thoracic SCI that manifest cardiovascular dysfunction, as well as contemporary research methodologies being employed to unveil the precise contribution of PN plasticity to the pathophysiology underlying AD development.
PubMed: 31780900
DOI: 10.3389/fncel.2019.00505 -
Comparative Biochemistry and... Feb 2020Using long-term, remote recordings of heart rate (f) on fully recovered, undisturbed lizards, we identified several components of heart rate variability (HRV) associated...
Using long-term, remote recordings of heart rate (f) on fully recovered, undisturbed lizards, we identified several components of heart rate variability (HRV) associated with respiratory sinus arrhythmia (RSA): 1.) A peak in the spectral representation of HRV at the frequency range of ventilation. 2.) These cardiorespiratory interactions were shown to be dependent on the parasympathetic arm of the autonomic nervous system. 3.) Vagal preganglionic neurons are located in discrete groups located in the dorsal motor nucleus of the vagus and also, in a ventro-lateral group, homologous to the nucleus ambiguus of mammals. 4.) Myelinated nerve fibers in the cardiac vagus enabling rapid communication between the central nervous system and the heart. Furthermore, the study of the progressive recovery of f in tegu following anesthesia and instrumentation revealed that 'resting' levels of mean f and reestablishment of HRV occurred over different time courses. Accordingly, we suggest that, when an experiment is designed to study a physiological variable reliant on autonomic modulation at its normal, resting level, then postsurgical reestablishment of HRV should be considered as the index of full recovery, rather than mean f.
Topics: Anesthesia; Animals; Autonomic Nervous System; Heart; Heart Rate; Lizards; Male; Models, Theoretical; Recovery of Function; Respiration; Vagus Nerve
PubMed: 31707060
DOI: 10.1016/j.cbpa.2019.110607 -
Experimental Neurology Jan 2020Spinal cord injury (SCI) can have profound effects on the autonomic and cardiovascular systems, notably with injuries above high-thoracic levels that result in the...
Spinal cord injury (SCI) can have profound effects on the autonomic and cardiovascular systems, notably with injuries above high-thoracic levels that result in the development of autonomic dysreflexia (AD) characterized by volatile hypertension in response to exaggerated sympathetic reflexes triggered by afferent stimulation below the injury level. Pathophysiological changes associated with the development of AD include sprouting of both nociceptive afferents and ascending propriospinal 'relay' neurons below the injury, as well as dynamic changes in synaptic inputs onto sympathetic preganglionic neurons. However, it remains uncertain whether synapse formation between sprouted c-fibers and propriospinal neurons contributes to the development of exaggerated sympathetic reflexes produced during AD. We previously reported that once daily treatment with the anti-epileptic and neuropathic pain medication, gabapentin (GBP), at low dosage (50 mg/kg) mitigates experimentally induced AD soon after injections, likely by impeding glutamatergic signaling. Since much higher doses of GBP are reported to block the formation of excitatory synapses, we hypothesized that continuous, high dosage GBP treatment after SCI might prevent the formation of aforementioned aberrant synapses and, accordingly, reduce the incidence and severity of AD. Adult female rats implanted with aortic telemetry probes for hemodynamic monitoring underwent T4-transection SCI and immediately received 100 mg/kg (i.p.) of GBP and then every six hours (400 mg/kg/day) for 4-weeks after injury. We assessed daily body weight, mean arterial pressure, heart rate, frequency of spontaneous AD, and hemodynamic changes during colorectal distension (CRD) to establish whether high dose GBP treatment prophylactically mitigates both AD and associated aberrant synaptic plasticity. This regimen significantly reduced both the absolute blood pressure reached during experimentally induced AD and the time required to return to baseline afterwards. Conversely, GBP prevented return to pre-injury body weights and paradoxically increased the frequency of spontaneously occurring AD. While there were significant decreases in the densities of excitatory and inhibitory pre-synaptic markers in the lumbosacral dorsal horn following injury alone, they were unaltered by continuous GBP treatment. This indicates distinct mechanisms of action for acute GBP to mitigate induced AD whereas chronic GBP increases non-induced AD frequencies. While high dose prophylactic GBP is not recommended to treat AD, acute low dose GBP may hold therapeutic value to mitigate evoked AD, notably during iatrogenic procedures under controlled clinical conditions.
Topics: Animals; Autonomic Dysreflexia; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists; Female; Gabapentin; Neuronal Plasticity; Rats; Rats, Wistar; Spinal Cord; Spinal Cord Injuries
PubMed: 31678138
DOI: 10.1016/j.expneurol.2019.113083 -
Neurology Aug 2019
Topics: Autonomic Dysreflexia; Autonomic Fibers, Preganglionic; Humans; Interneurons; Male; Spinal Cord; Spinal Cord Injuries; Sympathetic Nervous System
PubMed: 31308152
DOI: 10.1212/WNL.0000000000007973 -
Nature Neuroscience Aug 2019The effects of autonomic innervation of tumors on tumor growth remain unclear. Here we developed a series of genetic techniques to manipulate autonomic innervation in a...
The effects of autonomic innervation of tumors on tumor growth remain unclear. Here we developed a series of genetic techniques to manipulate autonomic innervation in a tumor- and fiber-type-specific manner in mice with human breast cancer xenografts and in rats with chemically induced breast tumors. Breast cancer growth and progression were accelerated following stimulation of sympathetic nerves in tumors, but were reduced following stimulation of parasympathetic nerves. Tumor-specific sympathetic denervation suppressed tumor growth and downregulated the expression of immune checkpoint molecules (programed death-1 (PD-1), programed death ligand-1 (PD-L1), and FOXP3) to a greater extent than with pharmacological α- or β-adrenergic receptor blockers. Genetically induced simulation of parasympathetic innervation of tumors decreased PD-1 and PD-L1 expression. In humans, a retrospective analysis of breast cancer specimens from 29 patients revealed that increased sympathetic and decreased parasympathetic nerve density in tumors were associated with poor clinical outcomes and correlated with higher expression of immune checkpoint molecules. These findings suggest that autonomic innervation of tumors regulates breast cancer progression.
Topics: Adrenergic Antagonists; Animals; Autonomic Fibers, Preganglionic; B7-H1 Antigen; Breast Neoplasms; Denervation; Disease Progression; Female; Forkhead Transcription Factors; Heterografts; Humans; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Parasympathetic Nervous System; Programmed Cell Death 1 Receptor; Rats; Retrospective Studies; Stress, Psychological; Sympathetic Nervous System
PubMed: 31285612
DOI: 10.1038/s41593-019-0430-3