Humans ; Locomotion ; Mesencephalon ; Midbrain Reticular Formation ; Parkinson Disease

Central hypoventilation syndrome is a rare and fatal condition resulting from various central nervous system disorders that is characterized by a failure of automatic breathing. We report a case of central hypoventilation syndrome following posterior circulation stroke whose pulmonary function was improved by respiratory rehabilitation. A 59-year-old woman with a history of hemorrhagic stroke of the bilateral cerebellum was hospitalized due to pneumonia. A portable ventilator was applied via tracheostomy, recurrent episodes of apnea and hypercapnia impeded weaning. A respiratory rehabilitation program including chest wall range of motion exercise, air stacking exercise, neuromuscular electrical stimulation (NMES) on abdominal muscles, upper extremity ergometer, locomotor training, high-frequency chest wall oscillator, mechanical insufflation, and exsufflation was employed, as spirometry showed a severe restrictive pattern. A spontaneous breathing trial was started, and a portable ventilator was applied for 8 hours, only during nighttime, to prevent sudden apneic event. After 4 weeks of treatment, follow-up spirometry showed much improved respiratory parameters. This case suggests that respiratory rehabilitation can improve pulmonary function parameters and quality of life in central hypoventilation syndrome.
Abdominal Muscles ; Apnea ; Central Nervous System Diseases ; Cerebellum ; Electric Stimulation ; Female ; Follow-Up Studies ; Humans ; Hypercapnia ; Hypoventilation ; Insufflation ; Middle Aged ; Pneumonia ; Quality of Life ; Range of Motion, Articular ; Rehabilitation ; Respiration ; Respiratory Center ; Spirometry ; Stroke ; Thoracic Wall ; Tracheostomy ; Upper Extremity ; Ventilators, Mechanical ; Weaning

Formalin-inactivated respiratory syncytial virus (RSV) vaccination causes vaccine-enhanced disease (VED) after RSV infection. It is considered that vaccine platforms enabling endogenous synthesis of RSV immunogens would induce favorable immune responses than non-replicating subunit vaccines in avoiding VED. Here, we investigated the immunogenicity, protection, and disease in mice after vaccination with RSV fusion protein (F) encoding plasmid DNA (F-DNA) or virus-like particles presenting RSV F (F-VLP). F-DNA vaccination induced CD8 T cells and RSV neutralizing Abs, whereas F-VLP elicited higher levels of IgG2a isotype and neutralizing Abs, and germinal center B cells, contributing to protection by controlling lung viral loads after RSV challenge. However, mice that were immunized with F-DNA displayed weight loss and pulmonary histopathology, and induced F specific CD8 T cell responses and recruitment of monocytes and plasmacytoid dendritic cells into the lungs. These innate immune parameters, RSV disease, and pulmonary histopathology were lower in mice that were immunized with F-VLP after challenge. This study provides important insight into developing effective and safe RSV vaccines.
Animals ; B-Lymphocytes ; Dendritic Cells ; DNA ; Germinal Center ; Immunoglobulin G ; Lung ; Mice ; Monocytes ; Plasmids ; Respiratory Syncytial Virus Vaccines ; Respiratory Syncytial Viruses ; T-Lymphocytes ; Vaccination ; Vaccines, Subunit ; Viral Load ; Weight Loss

Premature birth is a leading cause of infant mortality which is often attributed to irregular breathing and apnea of prematurity. A common treatment for apnea is caffeine to stimulate the brain's respiratory center. However, caffeine's long term effect on infant development is not fully comprehended. We hypothesized that noninvasive localized body stimulation regularizes breathing pattern. We investigated the impact of electrical or mechanical stimulation on breathing in mice. After the mice were ventilated for 28 s to induce apnea, mice were taken off the ventilator while receiving mechanical, electrical, or no stimulation in a randomized order. Both stimuli targeted the diaphragm area through a custom-built belt with vibrating motors or adhesive electrodes. After each apnea cycle, the time to take the first breath (T) was recorded. The electrical stimulation given at 4.5, 8.3, 16.7 V (pulse rate = 3 Hz, pulse width = 120 μs) showed no reduction in T. Electrical stimulation at pulse rates of 10 or 20 Hz (16.7 V, pulse width 260 μs) showed a detrimental effect increasing T by ~ 7% compared to control values (p = 0.005, p = 0.038 respectively). High and medium intensity mechanical stimulations significantly reduced T by 11.74 (p<10⁻¹³) and by 17.08% (p<10⁻⁸), respectively. Further reducing the amplitude of vibrations did not affect T. When the probe was attached to the ankles, only the high intensity vibrations resulted in a decrease in T (p<10⁻¹³). Mechanical vibrations, applied at various intensities and locations, could be used to treat irregular breathing and apnea in infants.
Adhesives ; Animals ; Ankle ; Apnea* ; Caffeine ; Child ; Child Development ; Diaphragm ; Electric Stimulation* ; Electrodes ; Heart Rate ; Humans ; Infant ; Infant Mortality ; Mice* ; Premature Birth ; Respiration ; Respiratory Center ; Ventilators, Mechanical ; Vibration

The relationship between the vestibular system and the autonomic nervous system has been well studied in the context of the maintenance of homeostasis to the changing internal and external milieus. The perturbations of the autonomic indexes to the vestibular stimuli have been demonstrated in animal studies. In addition, the fluctuation of the blood pressure and the heart rate with other autonomic symptoms such as nausea, vomiting, and pallor are common manifestations in the wide range of vestibular disorders. At the same time, the disorders of the autonomic nervous system can cause dizziness and vertigo in some group of patients. In the anatomical point of view, the relationship between autonomic and vestibular systems is evident. The afferent signals from each system converge to the nucleus of solitary tract to be integrated in medullary reticular formation and the each pathway from the vestibular and autonomic nervous system is interconnected from medulla to cerebral cortex. In this paper, the reported evidence demonstrating the relationship between autonomic derangement and vestibular disorders is reviewed and the further clinical implications are discussed.
Animals ; Autonomic Nervous System ; Autonomic Nervous System Diseases ; Blood Pressure ; Cerebral Cortex ; Dizziness ; Heart Rate ; Homeostasis ; Humans ; Nausea ; Pallor ; Reticular Formation ; Solitary Nucleus ; Vertigo ; Vomiting

The characteristic features of Alzheimer's disease (AD) are the appearance of extracellular amyloid-beta (Aβ) plaques and neurofibrillary tangles in the intracellular environment, neuronal death and the loss of synapses, all of which contribute to cognitive decline in a progressive manner. A number of hypotheses have been advanced to explain AD. Abnormal tau phosphorylation may contribute to the formation of abnormal neurofibrillary structures. Many different structures are susceptible to AD, including the reticular formation, the nuclei in the brain stem (e.g., raphe nucleus), thalamus, hypothalamus, locus ceruleus, amygdala, substantia nigra, striatum, and claustrum. Excitotoxicity results from continuous, low-level activation of N-methyl-D-aspartate (NMDA) receptors. Premature synaptotoxicity, changes in neurotransmitter expression, neurophils loss, accumulation of amyloid β-protein deposits (amyloid/senile plaques), and neuronal loss and brain atrophy are all associated with stages of AD progression. Several recent studies have examined the relationship between Aβ and NMDA receptors. Aβ-induced spine loss is associated with a decrease in glutamate receptors and is dependent upon the calcium-dependent phosphatase calcineurin, which has also been linked to long-term depression.
Alzheimer Disease* ; Amygdala ; Amyloid ; Animals, Genetically Modified ; Atrophy ; Basal Ganglia ; Brain Stem ; Brain* ; Calcineurin ; Depression ; Hypothalamus ; Locus Coeruleus ; N-Methylaspartate* ; Neurofibrillary Tangles ; Neurons ; Neurotransmitter Agents ; Pathology* ; Phosphorylation ; Receptors, Glutamate ; Receptors, N-Methyl-D-Aspartate* ; Reticular Formation ; Risk Factors* ; Spine ; Substantia Nigra ; Synapses ; tau Proteins* ; Thalamus

The use of alcohol is associated with the development and worsening of sleep disorder. Alcohol is generally known to have a sedative effect, but it has an arousal or sedative effect depending on the timing and drinking dose and directly affects REM sleep physiology. Alcohol acts on the central nervous system (CNS) to interfere with the sleep-wake cycle and to affect sleep-related hormone secretion. In addition, the ingestion of alcohol pre-sleep is associated with deterioration and development of sleep related breathing disorders (SBD). The increase in resistance of the upper respiratory tract and the decrease in sensitivity of the CNS respiratory center and the respiratory muscles are major mechanisms of alcohol-induced SBD, and result in snoring or apnea in healthy men or aggravating apnea in patients with OSA. Sleep-related restless leg syndrome and circadian rhythm disorders are common in alcohol use disorder patients. This review provides an assessment of scientific studies that investigated on the impact of alcohol ingestion on nocturnal sleep physiology and sleep disorders.
Alcohols ; Apnea ; Arousal ; Central Nervous System ; Chronobiology Disorders ; Drinking ; Eating ; Humans ; Hypnotics and Sedatives ; Male ; Physiology ; Respiration ; Respiratory Center ; Respiratory Muscles ; Respiratory System ; Restless Legs Syndrome ; Sleep Apnea Syndromes ; Sleep Wake Disorders* ; Sleep, REM ; Snoring

BACKGROUND: Recent studies have shown that the nontuberculosis mycobacterium (NTM) recovery rate in clinical cultures has increased within Korea. However, another study conducted by a secondary hospital within Daegu reported different results. Therefore, the purpose of this study is to understand and evaluate the microbiological distribution and clinical features of NTM in Daegu. METHODS: A retrospective study was conducted on 11,672 respiratory specimens undergoing acid fast bacilli (AFB) culture from 6,685 subjects who visited Yeungnam University Respiratory Center from January 2012 to December 2013. RESULTS: Of the 11,672 specimens undergoing AFB culture, 1,310 specimens (11.2%) showed positive results. Of these specimens, NTM was recovered from 587 specimens, showing a recovery rate of 44.8%. Identification test for NTM was performed on 191 subjects; the results were as follows: M. avium-intracellulare complex (MAC) 123 (64.4%), M. abscessus 20 (10.5%), M. kansasii 12 (6.3%), and 33 other NTM germ strains. Of the 382 subjects with NTM, 167 were diagnosed with pulmonary NTM disease (43.7%), however virulence differed depending on NTM strain. Multivariate analysis showed that nodular bronchiectasis, the nodules, and finding consistent with cavity under imaging study were statistically significant for triggering pulmonary NTM disease. AFB culture showing MAC and M. abscessus was statistically significant as well. Positive predictive value for NTM polymerase chain reaction (NTM-PCR) was 88.6%. CONCLUSION: Results for NTM recovery rate within the Daegu area were similar to those for the Seoul metropolitan area. We can assume that NTM infection is increasing in our community, therefore AFB-positive subjects (1) should undergo NTM-PCR, (2) should have their culture results checked for differentiation of mycobacterium tuberculosis complex (MTB) from NTM, and (3) undergo NTM identification test to confirm its type. Administration of treatment with the above results should be helpful in improving the patients' prognosis.
Bronchiectasis ; Daegu* ; Korea ; Lung Diseases ; Multivariate Analysis ; Mycobacterium ; Mycobacterium tuberculosis ; Nontuberculous Mycobacteria* ; Polymerase Chain Reaction ; Prognosis ; Respiratory Center ; Retrospective Studies ; Seoul ; Tertiary Care Centers* ; Virulence

Substantial evidence has suggested that deep brain stimulation of the cuneiform nucleus has become a remarkable treatment option for intractable pain, but the possible mechanism is poorly understood. Using a melanocortin-4 receptor (MC4R)-green fluorescent protein (GFP) reporter knockin mouse, we showed that a large number of MC4R-GFP-positive neurons were expressed in the cuneiform nucleus. Immunofluorescence revealed that approximately 40%-50% of MC4R-GFP-positive neurons expressed mu opioid receptors, indicating that they were opioidergic signaling. Our findings support the hypothesis that MC4R expression in the cuneiform nucleus is involved in the modulation of opioidergic signaling.
Animals ; Gene Expression Regulation ; Gene Knock-In Techniques ; Genes, Reporter ; Green Fluorescent Proteins ; genetics ; metabolism ; Mice ; Mice, Transgenic ; Microtomy ; Midbrain Reticular Formation ; cytology ; metabolism ; Neurons ; cytology ; metabolism ; Receptor, Melanocortin, Type 4 ; genetics ; metabolism ; Receptors, Opioid, mu ; genetics ; metabolism ; Recombinant Fusion Proteins ; genetics ; metabolism ; Signal Transduction

The brain stem consists of medulla oblongta, pons and midbrain. It is sited in posterior cranial fossa. It contains numerous intrinsic neuron cell bodies and their processes, some of which are the brain stem homologues of spinal neuronal groups. These include the sites of termination and cells of origin of axons that enter or leave the brain stem through the cranial nerves. Cranial nerves provide sensory, motor and autonomic innervations of structures that are mostly in the head and neck. The reticular formation is an extensive network of neurons that extends throughout the length of brain stem and is continuous rostrally to diencephalon and caudally to its spinal counterpart. Clinically, damage to the brain stem is often devastating and life threatening. This is because it is a structurally and functionally compact region. Therefore, it is important to build basic knowledge about neuroanatomy of brain stem.
Axons ; Brain Stem* ; Cranial Fossa, Posterior ; Cranial Nerves ; Diencephalon ; Head ; Mesencephalon ; Neck ; Neuroanatomy* ; Neurons ; Pons ; Reticular Formation