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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 -
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 -
Neurotrauma Reports 2022Spinal cord injury (SCI) significantly impacts many systems attributable to disrupted autonomic regulation of the body. Of these disruptions, excessive...
Spinal cord injury (SCI) significantly impacts many systems attributable to disrupted autonomic regulation of the body. Of these disruptions, excessive production/passage of urine (polyuria) has been understudied. Pre-clinical animal studies investigating SCI-induced polyuria have been carried out in T8-T10 spinal-level contusive injuries, which directly impacts both supraspinal sympathetic inputs to the spinal circuitry mediating kidney function as well as local networks including pre-ganglionic sympathetic fibers to the kidney. The current study utilizes a higher-level (T3) contusion to narrow the potential source(s) of damage that induce(s) polyuria. Metabolic cage 24-h urine collections demonstrated that, starting 1 week post-SCI and lasting chronically through 6 weeks post-SCI, T3 contused adult male rats had a significant increase in void volume relative to pre-injury and surgical sham controls. Subsequent examination of previously identified biomarkers revealed levels reflecting the presence of polyuria. For example, urine atrial natriuretic peptide levels were significantly increased at 6 weeks post-SCI compared to baseline, and serum arginine vasopressin (AVP) levels were significantly decreased. Further, there was a significant decrease post-injury relative to shams in the number of AVP-labeled cells within the suprachiasmatic nucleus, a hypothalamic region responsible for significant disruptions of circadian rhythmicity post-SCI, including loss of the diurnal variation of AVP production, which clinical studies have identified as contributing to the emergence of nocturia after SCI. Together, the current results demonstrate that SCI-induced polyuria is present after a T3-level SCI, indicating that damage of descending supraspinal circuitries precipitates dysfunction of homeostatic mechanisms involved in salt and water balance.
PubMed: 35558732
DOI: 10.1089/neur.2022.0014 -
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 -
Autonomic Neuroscience : Basic &... Sep 2020The central adrenergic and noradrenergic neurotransmitter systems diffusively affect the operation of the spinal neural network and dynamically gauge central sympathetic...
The central adrenergic and noradrenergic neurotransmitter systems diffusively affect the operation of the spinal neural network and dynamically gauge central sympathetic outflow. Using in vitro splanchnic nerve-thoracic spinal cord preparations as an experimental model, this study examined the intraspinal α-adrenoceptor-meidated modulation of sympathetic firing behaviors. Several sympathetic single-fiber activities were simultaneously recorded. Application of phenylephrine (Phe, an α-adrenoceptor agonist) increased, decreased or did not affect spontaneous firing. A log-log plot of the change ratios of the average firing rates (AFR) versus their basal AFR displays a linear data distribution. Thus, the heterogeneity in α-adrenoceptor-mediated responses is well described by a power law function. Phe-induced power-law firing modulation (plFM) was sensitive to prazosin (Prz, an α-adrenoceptor antagonist). Heparin (Hep, a competitive IP receptor blocker) and chelerythrine (Che, a protein kinase C inhibitor) also caused plFM. Phe-induced plFM persisted in the presence of Hep; however, it was occluded by Che pretreatment. Pair-wise analysis of single-fiber activities revealed synchronous sympathetic discharges. Application of Phe, Hep or Che suppressed synchronous discharges in fiber pairs with apparent correlated firing (ACF) and induced or potentiated synchronous discharges in those without or with minimal ACF. Thus, the basal activities of the sympathetic preganglionic neurons participate in determining the responses mediated by the activation of α-adrenoceptors. This deterministic factor, which is intrinsic to spinal neural networks, helps the supraspinal adrenergic and noradrenergic systems differentially control their widely distributed neural targets.
Topics: Adrenergic alpha-1 Receptor Antagonists; Animals; Animals, Newborn; Electrophysiological Phenomena; Heparin; Inositol 1,4,5-Trisphosphate Receptors; Nerve Net; Prazosin; Protein Kinase C; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, alpha-1; Spinal Cord; Sympathetic Nervous System
PubMed: 32502943
DOI: 10.1016/j.autneu.2020.102688 -
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 -
International Journal of Cardiology Oct 2019Insular cortex (IC) ischemic strokes are associated with increased risk of cardiac arrhythmias. We have previously hypothesized that the anatomical substrate for...
BACKGROUND
Insular cortex (IC) ischemic strokes are associated with increased risk of cardiac arrhythmias. We have previously hypothesized that the anatomical substrate for post-stroke neurogenic arrhythmias comprises stroke-induced left atrium (LA) coronary microvascular endothelial dysfunction (CMED), and myocardial inflammatory infiltration (MII) leading to myocardial fibrosis. We investigated whether selectively induced IC ischemic stroke in rats results in histopathological changes in the LA.
METHODS
Insular ischemic stroke was induced in 6-month old male Wistar rats via unilateral stereotaxic injection of endothelin-1 into the left or right IC. The control group consisted of rats injected with saline. We histologically examined the LA 28 days after stroke for CMED, MII, and fibrosis. We performed linear regression analyses to assess correlation between the 3 histopathological outcomes. We compared these findings in the distal LA and the LA-pulmonary vein border (LA-PV border), a region of rich autonomic innervation.
RESULTS
Right and left IC stroke led to CMED, MII, and fibrosis in the LA. MII was significantly correlated with CMED and fibrosis. The LA-PV border had significantly greater MII and fibrosis than the distal LA. There were no differences in coronary microvascular and myocardial changes between left and right IC strokes.
CONCLUSIONS
Left and right insular ischemic strokes resulted in CMED, MII, and fibrosis, the pathological hallmark of arrhythmogenic LA tissue. Since these changes were greater within the LA-PV border than in the distal LA tissue, the role of preganglionic fibers at the ganglionated plexi as part of neurogenic arrhythmogenesis warrants further investigation.
Topics: Animals; Atrial Function, Left; Brain Ischemia; Cerebral Cortex; Endothelium, Vascular; Fibrosis; Male; Microvessels; Myocarditis; Myocardium; Rats; Rats, Wistar; Stroke
PubMed: 31196685
DOI: 10.1016/j.ijcard.2019.06.004