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Journal of Cardiovascular Development... Nov 2022Cardiac denervation is a serious problem in a number of patients, including patients after heart transplantation. The status of the parasympathetic ganglia after...
Cardiac denervation is a serious problem in a number of patients, including patients after heart transplantation. The status of the parasympathetic ganglia after crossing the preganglionic fibers of the vagus nerve has not been enough studied. The aim of our study was to assess the effect of physical training on the morphological parameters of the parasympathetic atrial ganglia and autonomic regulation of heart rate after right- and left-sided vagotomy in rats. Morphometric characteristics of the right atrial ganglia were evaluated using an immunohistochemical method after a study that included a three-time assessment of heart rate variability. It was found that right-sided vagotomy leads to both an increase in the volume of ganglion and autonomic dysfunction. No significant change in the number of nerve cells was found in animals with false and left-sided vagotomy while maintaining preganglionic innervation after the physical training, whereas exercises led to a decrease in the volume of nerve tissue of rats with right-sided denervation. It was also found that in animals with preserved vagal innervation, the volume of atrial ganglion tissue correlates with overall heart rate variability and a normalized parasympathetic component. Therefore, a positive effect from regular physical activity on parasympathetic regulation can be expected only if preganglionic vagal influence is preserved.
PubMed: 36421926
DOI: 10.3390/jcdd9110391 -
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 -
The Egyptian Heart Journal : (EHJ) :... Sep 2022Acute cervical spinal trauma may lead to cardiac effects by influencing cardiac sympathetic preganglionic fibers. Some of these effects, which are vital, may occur in...
BACKGROUND
Acute cervical spinal trauma may lead to cardiac effects by influencing cardiac sympathetic preganglionic fibers. Some of these effects, which are vital, may occur in ECG.
CASE PRESENTATION
A 52-year-old female patient admitted to the emergency department with acute traumatic spondylolisthesis at C6-C7 level and paraplegia. Positive QRS complex, ST segment depressions and prolongation of QTc interval were observed on ECG according to sudden autonomic disruption because of sympathetic nerve compression. It was mentioned that changes in QRS complex axis was normal which was dependent to the ECG display format of Cabrera sequence used differently from the classical system. After surgical correction, evident ST depressions were recovered and QTc intervalwas narrowed but still prolonged in control ECG.
CONCLUSIONS
Autonomic dysfunction can lead to extraordinary electrocardiographic presentation including widespread ST depressions with prolonged QTc interval. However, when evaluating the changes in the ECG, attention should be paid to ECG display format to avoid errors in interpretation.
PubMed: 36057680
DOI: 10.1186/s43044-022-00301-w -
Anatomical Science International Sep 2015The route of fine fascicles of nerve fibers in the lingual nerve was clarified. Contemporary anatomy textbooks describe the lingual nerve as supplying sensory...
The route of fine fascicles of nerve fibers in the lingual nerve was clarified. Contemporary anatomy textbooks describe the lingual nerve as supplying sensory innervation to the mucous membrane of the presulcal part of the tongue, the floor and side wall of the mouth, and the mandibular gums. In addition to receiving the chorda tympani and a branch of the inferior alveolar nerve, the lingual nerve is connected to the submandibular ganglion by a few branches. It carries preganglionic fibers from the chorda tympani and postganglionic fibers from the submandibular ganglion to the submandibular and sublingual glands. The branch from the mylohyoid nerve is described as a sensory nerve. However, we observed that this branch was directly connected to the submandibular ganglion. Furthermore, the branch from the submandibular ganglion innervated thin membranous tissue that originated in the petrous part of the temporal bone and inserted into the lateral surface of the superior constrictor. These branches have not been described in the anatomy textbooks and literature. Therefore, we studied the morphological features of the lingual nerve and discovered the route of fine fascicles of nerve fibers in the lingual nerve. These findings will likely improve the neurological and physiological understanding of the function of the lingual nerve.
Topics: Cadaver; Female; Humans; Lingual Nerve; Male; Nerve Fibers
PubMed: 25467528
DOI: 10.1007/s12565-014-0267-5 -
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 -
Brain Stimulation 2021Electrical stimulation applied to individual organs, peripheral nerves, or specific brain regions has been used to treat a range of medical conditions. In cardiovascular...
BACKGROUND
Electrical stimulation applied to individual organs, peripheral nerves, or specific brain regions has been used to treat a range of medical conditions. In cardiovascular disease, autonomic dysfunction contributes to the disease progression and electrical stimulation of the vagus nerve has been pursued as a treatment for the purpose of restoring the autonomic balance. However, this approach lacks selectivity in activating function- and organ-specific vagal fibers and, despite promising results of many preclinical studies, has so far failed to translate into a clinical treatment of cardiovascular disease.
OBJECTIVE
Here we report a successful application of optogenetics for selective stimulation of vagal efferent activity in a large animal model (sheep).
METHODS AND RESULTS
Twelve weeks after viral transduction of a subset of vagal motoneurons, strong axonal membrane expression of the excitatory light-sensitive ion channel ChIEF was achieved in the efferent projections innervating thoracic organs and reaching beyond the level of the diaphragm. Blue laser or LED light (>10 mW mm; 1 ms pulses) applied to the cervical vagus triggered precisely timed, strong bursts of efferent activity with evoked action potentials propagating at speeds of ∼6 m s.
CONCLUSIONS
These findings demonstrate that in species with a large, multi-fascicled vagus nerve, it is possible to stimulate a specific sub-population of efferent fibers using light at a site remote from the vector delivery, marking an important step towards eventual clinical use of optogenetic technology for autonomic neuromodulation.
Topics: Animals; Mammals; Motor Neurons; Optogenetics; Rats; Sheep; Vagus Nerve; Vagus Nerve Stimulation
PubMed: 33217609
DOI: 10.1016/j.brs.2020.11.010 -
Journal of the Neurological Sciences Sep 2017The detailed pathophysiology of limb coldness in multiple system atrophy (MSA) is unknown.
BACKGROUND
The detailed pathophysiology of limb coldness in multiple system atrophy (MSA) is unknown.
METHODS
We evaluated cutaneous vasomotor neural function in 18 MSA patients with or without limb coldness, and in 20 healthy volunteers as controls. We measured resting skin sympathetic nerve activity (SSNA) and spontaneous changes of the sympathetic skin response (SSR) and skin blood flow (skin vasomotor reflex: SVR), as well as SVR and reflex changes of SSNA after electrical stimulation. The parameters investigated were the SSNA frequency at rest, amplitude of SSNA reflex bursts, absolute decrease and percent reduction of SVR, recovery time, and skin blood flow velocity.
RESULTS
Both the resting frequency of SSNA and the amplitude of SSNA reflex bursts were significantly lower in the MSA group than the control group (p<0.001 and p<0.05, respectively). There were no significant differences between the two groups with regard to the absolute decrease or percent reduction of SVR volume. The recovery time showed no significant difference between all MSA patients and control groups, but it was significantly prolonged in six MSA patients with limb coldness compared with that in the control group and that in MSA patients without limb coldness (p<0.01). The skin blood flow velocity was significantly slower in the MSA group than in the control group (p<0.001).
CONCLUSION
In MSA patients, limb coldness might occur due to impairments of the peripheral circulation based on prolongation of vasoconstriction and a decrease of skin blood flow velocity secondary to combined pre- and postganglionic skin vasomotor dysfunction.
Topics: Aged; Autonomic Fibers, Postganglionic; Autonomic Fibers, Preganglionic; Blood Flow Velocity; Electric Stimulation; Female; Humans; Laser-Doppler Flowmetry; Male; Middle Aged; Multiple System Atrophy; Reflex; Skin; Sympathetic Fibers, Postganglionic; Vascular Diseases; Vasoconstriction
PubMed: 28870566
DOI: 10.1016/j.jns.2017.07.018 -
Spinally projecting preproglucagon axons preferentially innervate sympathetic preganglionic neurons.Neuroscience Jan 2015Glucagon-like peptide-1 (GLP-1) affects central autonomic neurons, including those controlling the cardiovascular system, thermogenesis, and energy balance....
Glucagon-like peptide-1 (GLP-1) affects central autonomic neurons, including those controlling the cardiovascular system, thermogenesis, and energy balance. Preproglucagon (PPG) neurons, located mainly in the nucleus tractus solitarius (NTS) and medullary reticular formation, produce GLP-1. In transgenic mice expressing glucagon promoter-driven yellow fluorescent protein (YFP), these brainstem PPG neurons project to many central autonomic regions where GLP-1 receptors are expressed. The spinal cord also contains GLP-1 receptor mRNA but the distribution of spinal PPG axons is unknown. Here, we used two-color immunoperoxidase labeling to examine PPG innervation of spinal segments T1-S4 in YFP-PPG mice. Immunoreactivity for YFP identified spinal PPG axons and perikarya. We classified spinal neurons receiving PPG input by immunoreactivity for choline acetyltransferase (ChAT), nitric oxide synthase (NOS) and/or Fluorogold (FG) retrogradely transported from the peritoneal cavity. FG microinjected at T9 defined cell bodies that supplied spinal PPG innervation. The deep dorsal horn of lower lumbar cord contained YFP-immunoreactive neurons. Non-varicose, YFP-immunoreactive axons were prominent in the lateral funiculus, ventral white commissure and around the ventral median fissure. In T1-L2, varicose, YFP-containing axons closely apposed many ChAT-immunoreactive sympathetic preganglionic neurons (SPN) in the intermediolateral cell column (IML) and dorsal lamina X. In the sacral parasympathetic nucleus, about 10% of ChAT-immunoreactive preganglionic neurons received YFP appositions, as did occasional ChAT-positive motor neurons throughout the rostrocaudal extent of the ventral horn. YFP appositions also occurred on NOS-immunoreactive spinal interneurons and on spinal YFP-immunoreactive neurons. Injecting FG at T9 retrogradely labeled many YFP-PPG cell bodies in the medulla but none of the spinal YFP-immunoreactive neurons. These results show that brainstem PPG neurons innervate spinal autonomic and somatic motor neurons. The distributions of spinal PPG axons and spinal GLP-1 receptors correlate well. SPN receive the densest PPG innervation. Brainstem PPG neurons could directly modulate sympathetic outflow through their spinal inputs to SPN or interneurons.
Topics: Adrenergic Fibers; Animals; Axons; Bacterial Proteins; Choline O-Acetyltransferase; Female; Glucagon-Like Peptide-1 Receptor; Immunoenzyme Techniques; Interneurons; Luminescent Proteins; Male; Medulla Oblongata; Mice, Transgenic; Motor Neurons; Neuroanatomical Tract-Tracing Techniques; Nitric Oxide Synthase; Peritoneal Cavity; Posterior Horn Cells; Proglucagon; Sacrum; Stilbamidines; Thoracic Vertebrae
PubMed: 25450967
DOI: 10.1016/j.neuroscience.2014.10.043 -
Journal of Parkinson's Disease Apr 2016Loss of intermediolateral nucleus (IML) neurons is considered to play a major role in orthostatic hypotension (OH) of multiple system atrophy (MSA). In Parkinson disease...
BACKGROUND AND OBJECTIVE
Loss of intermediolateral nucleus (IML) neurons is considered to play a major role in orthostatic hypotension (OH) of multiple system atrophy (MSA). In Parkinson disease (PD) and dementia with Lewy bodies (DLB), autonomic phenomena such as OH are common and attributed to dysfunction of sympathetic, parasympathetic, and visceral autonomic neurons. However, apart from MSA, few reports have focused on the neuropathologic aspects in PD and DLB. Here we assessed IML degeneration as well as the fine myelinated fibers (FFs; maximum diameter less than 3 μm) considered to be preganglionic sympathetic nerve fibers derived from IML neurons in PD, DLB, MSA, and age-matched normal controls (NC).
METHODS
We counted IML neurons and measured the diameter and number of myelinated fibers of the ventral root at the level of the 12th thoracic segment.
RESULTS
Compared to NC, number of IML neurons and density of FF were significantly reduced in PD (53% and 67%), DLB (47% and 71%) and MSA (27% and 42%). Compared to combined group of PD and DLB without OH (OH-), IML neurons in combined group of PD and DLB with OH (OH+) were significantly reduced (77%). Compared to NC, FF densities in OH-, OH+ were significantly reduced (74% and 59%). The mean ratio of small to large myelinated fibers in OH+ (1.18), but not that in OH-(1.58), was significantly lower than that in NC (3.17).
CONCLUSIONS
We present neuropathological evidence that IML neurons and FFs in the ventral root are reduced in PD and DLB and that the reduction was more severe in the combined group of OH+ than in OH-.
Topics: Aged; Aged, 80 and over; Female; Humans; Hypotension, Orthostatic; Lewy Body Disease; Male; Nerve Fibers; Neurons; Parkinson Disease; Spinal Cord Lateral Horn; Spinal Nerve Roots
PubMed: 27061071
DOI: 10.3233/JPD-150773 -
Autonomic Neuroscience : Basic &... Mar 2018Immunohistochemistry is used widely to identify cholinergic neurons, but this approach has some limitations. To address these problems, investigators developed...
Immunohistochemistry is used widely to identify cholinergic neurons, but this approach has some limitations. To address these problems, investigators developed transgenic mice that express enhanced green fluorescent protein (GFP) directed by the promoter for choline acetyltransferase (ChAT), the acetylcholine synthetic enzyme. Although, it was reported that these mice express GFP in all cholinergic neurons and non-neuronal cholinergic cells, we could not detect GFP in cardiac cholinergic nerves in preliminary experiments. Our goals for this study were to confirm our initial observation and perform a qualitative screen of other representative autonomic structures for the presences of GFP in cholinergic innervation of effector tissues. We evaluated GFP fluorescence of intact, unfixed tissues and the cellular localization of GFP and vesicular acetylcholine transporter (VAChT), a specific cholinergic marker, in tissue sections and intestinal whole mounts. Our experiments identified two major tissues where cholinergic neurons and/or nerve fibers lacked GFP: 1) most cholinergic neurons of the intrinsic cardiac ganglia and all cholinergic nerve fibers in the heart and 2) most cholinergic nerve fibers innervating airway smooth muscle. Most cholinergic neurons in airway ganglia stained for GFP. Cholinergic systems in the bladder and intestines were fully delineated by GFP staining. GFP labeling of input to ganglia with long preganglionic projections (vagal) was sparse or weak, while that to ganglia with short preganglionic projections (spinal) was strong. Total absence of GFP might be due to splicing out of the GFP gene. Lack of GFP in nerve projections from GFP-positive cell bodies might reflect a transport deficiency.
Topics: Animals; Choline O-Acetyltransferase; Cholinergic Fibers; Cholinergic Neurons; Female; Ganglia, Sympathetic; Green Fluorescent Proteins; Male; Mice; Mice, Transgenic; Vesicular Acetylcholine Transport Proteins
PubMed: 29288022
DOI: 10.1016/j.autneu.2017.12.005