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Respiratory Physiology & Neurobiology Dec 2017The modulation of cough by microinjections of codeine in 3 medullary regions, the solitary tract nucleus rostral to the obex (rNTS), caudal to the obex (cNTS) and the...
The modulation of cough by microinjections of codeine in 3 medullary regions, the solitary tract nucleus rostral to the obex (rNTS), caudal to the obex (cNTS) and the lateral tegmental field (FTL) was studied. Experiments were performed on 27 anesthetized spontaneously breathing cats. Electromyograms (EMG) were recorded from the sternal diaphragm and expiratory muscles (transversus abdominis and/or obliquus externus; ABD). Repetitive coughing was elicited by mechanical stimulation of the intrathoracic airways. Bilateral microinjections of codeine (3.3 or 33mM, 54±16nl per injection) in the cNTS had no effect on cough, while those in the rNTS and in the FTL reduced coughing. Bilateral microinjections into the rNTS (3.3mM codeine, 34±1 nl per injection) reduced the number of cough responses by 24% (P<0.05), amplitudes of diaphragm EMG by 19% (P<0.01), of ABD EMG by 49% (P<0.001) and of expiratory esophageal pressure by 56% (P<0.001). Bilateral microinjections into the FTL (33mM codeine, 33±3 nl per injection) induced reductions in cough expiratory as well as inspiratory EMG amplitudes (ABD by 60% and diaphragm by 34%; P<0.01) and esophageal pressure amplitudes (expiratory by 55% and inspiratory by 26%; P<0.001 and 0.01, respectively). Microinjections of vehicle did not significantly alter coughing. Breathing was not affected by microinjections of codeine. These results suggest that: 1) codeine acts within the rNTS and the FTL to reduce cough in the cat, 2) the neuronal circuits in these target areas have unequal sensitivity to codeine and/or they have differential effects on spatiotemporal control of cough, 3) the cNTS has a limited role in the cough suppression induced by codeine in cats.
Topics: Abdominal Muscles; Animals; Antitussive Agents; Blood Pressure; Cats; Codeine; Cough; Diaphragm; Disease Models, Animal; Dose-Response Relationship, Drug; Electromyography; Female; Male; Medulla Oblongata; Microinjections; Respiratory Muscles
PubMed: 28778649
DOI: 10.1016/j.resp.2017.07.011 -
Anesthesiology Feb 2010Spinal transection or selective delivery of volatile anesthetics to the spinal cord reduces minimum alveolar concentration (MAC), whereas precollicular decerebration...
BACKGROUND
Spinal transection or selective delivery of volatile anesthetics to the spinal cord reduces minimum alveolar concentration (MAC), whereas precollicular decerebration does not. The authors sought to determine which brainstem regions influence anesthetic requirements and movement responses with isoflurane.
METHODS
Movement (biceps femoris electromyogram) and MAC were measured in adult rats before and after decerebration at the precollicular, mid-collicular, pontine or medullary level, or decerebellation. Additional experiments assessed the effects of lidocaine inactivation of the mesencephalic locomotor region on MAC and the effects of isoflurane on nociceptive neuronal responses in this region.
RESULTS
Transections placed at the level of the mid-colliculus, rostral pons, and pontomedullary junction significantly reduced MAC by approximately 10, 40, and 45%, respectively. MAC was decreased 9% after mid-medullary transections that were placed caudal to the nucleus raphe magnus but rostral to the dorsal reticular nucleus; however, only weak, single movements occurred. Caudal medullary transections at the obex decreased MAC by 60%. Bilateral inactivation of the mesencephalic locomotor region with lidocaine caused a reversible, 32% decrease in MAC and reduced the number and amplitude of movements at sub-MAC isoflurane concentrations. Neuronal responses of mesencephalic locomotor region neurons to supramaximal noxious tail clamp were reduced by 87% by 1.2 MAC isoflurane.
CONCLUSIONS
The authors conclude that the mesencephalic locomotor region influences anesthetic requirements and promotes repetitive movement with sub-MAC isoflurane by facilitating ventral spinal locomotor circuits, where anesthetics seem to exert their key immobilizing effects. However, net brainstem influences on MAC seem to result from interaction among descending nociceptive and locomotor modulatory pathways.
Topics: Anesthesia; Anesthetics, Inhalation; Anesthetics, Local; Animals; Brain Stem; Electromyography; Isoflurane; Lidocaine; Locomotion; Male; Microinjections; Movement; Neural Pathways; Neurons; Physical Stimulation; Pulmonary Alveoli; Rats; Rats, Sprague-Dawley
PubMed: 20098133
DOI: 10.1097/ALN.0b013e3181c81319 -
Veterinary Research Jun 2020In a study originally designed to find potential risk factors for bovine spongiform encephalopathy (BSE) we examined tissues from 403 Holstein Frisian cattle in total....
In a study originally designed to find potential risk factors for bovine spongiform encephalopathy (BSE) we examined tissues from 403 Holstein Frisian cattle in total. These included 20 BSE cattle and their 236 birth- and feeding cohort animals plus 32 offspring, 103 age, breed and district-matched control cattle and further twelve cattle with neurological signs. In addition to the obex, we examined the celiac ganglion, cervical cranial ganglion, trigeminal ganglion and proximal ganglion of the vagus nerve using histological techniques. Unexpectedly, we found a high number of neurofibroma, a benign peripheral nerve sheath tumor consisting of Schwann cells, fibroblasts and perineural cells. The neurofibroma were present only in the celiac ganglion and found during histologic examination. With a frequency of 9.91% in BSE cattle and their cohorts (case animals) and 9.09% in the age, breed and district matched control animals there seems to be no correlation between the occurrence of BSE and neurofibroma. Benign peripheral nerve sheath tumors have been described more often in cattle than in other domestic animals. Usually, they are incidental macroscopic findings in the thoracic ganglia during meat inspection. To our knowledge, there are no previous systematic histologic studies including bovine celiac ganglia at all. The high incidence of celiac ganglia neurofibroma may play a role in the frequently occurring abomasal displacements in Holstein Frisian cattle as the tumors might cause a gastrointestinal motility disorder. At present a genetic predisposition for these neoplasms cannot be ruled out.
Topics: Animals; Cattle; Cattle Diseases; Cohort Studies; Female; Ganglia, Sympathetic; Germany; Incidence; Male; Neurofibroma; Risk Factors
PubMed: 32552868
DOI: 10.1186/s13567-020-00800-1 -
Brain Research Nov 2009The anterior ethmoidal nerve (AEN) innervates the nasal passages and external nares, and serves as the afferent limb of the nasopharyngeal and diving responses. However,...
Unmyelinated fibers of the anterior ethmoidal nerve in the rat co-localize with neurons in the medullary dorsal horn and ventrolateral medulla activated by nasal stimulation.
The anterior ethmoidal nerve (AEN) innervates the nasal passages and external nares, and serves as the afferent limb of the nasopharyngeal and diving responses. However, although 65% of the AEN is composed of unmyelinated fibers, it has not been determined whether this afferent signal is carried by unmyelinated or myelinated fibers. We used the transganglionic tracers WGA-HRP, IB4-HRP, and CTB-HRP to trace the central projections of the AEN of the rat. Interpretation of the labeling patterns suggests that AEN unmyelinated fibers project primarily to the ventral tip of the ipsilateral medullary dorsal horn (MDH) at the level of the area postrema. Other unmyelinated projections were to the ventral paratrigeminal nucleus and ventrolateral medulla, specifically the Bötzinger and RVLM/C1 regions. Myelinated AEN fibers projected to the ventral paratrigeminal and mesencephalic trigeminal nuclei. Stimulating the nasal passages of urethane-anesthetized rats with ammonia vapors produced the nasopharyngeal response that included apnea, bradycardia and an increase in arterial blood pressure. Central projections of the AEN co-localized with neurons within both MDH and RVLM/C1 that were activated by nasal stimulation. Within the ventral MDH the density of AEN terminal projections positively correlated with the rostral-caudal location of activated neurons, especially at and just caudal to the obex. We conclude that unmyelinated AEN terminal projections are involved in the activation of neurons in the MDH and ventrolateral medulla that participate in the nasopharyngeal response in the rat. We also found that IB4-HRP was a much less robust tracer than WGA-HRP.
Topics: Analysis of Variance; Animals; Blood Pressure; Fluorescent Antibody Technique; Heart Rate; Image Processing, Computer-Assisted; Male; Medulla Oblongata; Microscopy, Fluorescence; Nasal Cavity; Nasopharynx; Nerve Fibers, Unmyelinated; Neural Pathways; Neuronal Tract-Tracers; Neurons; Odorants; Proto-Oncogene Proteins c-fos; Rats; Signal Processing, Computer-Assisted; Smell; Trigeminal Ganglion
PubMed: 19732757
DOI: 10.1016/j.brainres.2009.08.077 -
The Journal of Veterinary Medical... Nov 2021There has been no report on Chronic wasting disease (CWD) cases in Japan to date; however, there is concern about the geographic spread of CWD. To clarify the CWD status...
There has been no report on Chronic wasting disease (CWD) cases in Japan to date; however, there is concern about the geographic spread of CWD. To clarify the CWD status in Japan, we conducted CWD monitoring using real-time quaking-induced conversion (RT-QuIC) assay which can detect the low level of CWD prions. A total of 690 obex samples collected from sika deer and Reeves's muntjac in Hokkaido and Honshu was tested for CWD prions. No CWD-positive cases were found, suggesting that CWD is nonexistent in Japan. Our results also indicate that RT-QuIC assay is useful for continuous monitoring of CWD. Furthermore, nucleotide sequence analysis of the PrP gene revealed sika deer in Japan harbor CWD susceptible allele.
Topics: Animals; Biological Assay; Deer; Japan; Prions; Wasting Disease, Chronic
PubMed: 34556606
DOI: 10.1292/jvms.21-0368 -
The Journal of Veterinary Medical... May 2019A captured Japanese wild boar (Sus scrofa leucomystax) fetus was dicephalic. The fetus had two heads, but one body from the cranial neck region. Computed tomography...
A captured Japanese wild boar (Sus scrofa leucomystax) fetus was dicephalic. The fetus had two heads, but one body from the cranial neck region. Computed tomography imaging revealed that the two crania merged at the occipital bone, and the vertebral bodies between the atlas and the seventh thoracic vertebra were deformed. The fetus was found to have two tongues and laryngopharynges, but its esophagus and trachea were not duplicated. Each head contained a cerebrum and cerebellum, but the brains merged at the obex of the medulla oblongata, and the cervical spinal cord had duplicated ventral clefts. The heart was composed of three atria and four ventricles. This is the first report of a dicephalus with cardiac malformation in a wild boar.
Topics: Animals; Fetus; Heart Defects, Congenital; Japan; Sus scrofa; Tomography, X-Ray Computed; Twins, Conjoined
PubMed: 30853669
DOI: 10.1292/jvms.18-0765 -
Veterinary Microbiology Oct 2014Sheep scrapie is a transmissible spongiform encephalopathy (TSE), progressive and fatal neurodegenerative diseases of the central nervous system (CNS) linked to the...
Sheep scrapie is a transmissible spongiform encephalopathy (TSE), progressive and fatal neurodegenerative diseases of the central nervous system (CNS) linked to the accumulation of misfolded prion protein, PrP(Sc). New Zealand Cheviot sheep, homozygous for the VRQ genotype of the PRNP gene are most susceptible with an incubation period of 193 days with SSBP/1 scrapie. However, the earliest time point that PrP(Sc) can be detected in the CNS is 125 days (D125). The aim of this study was to quantify changes to the transcriptome of the thalamus and obex (medulla) at times immediately before (D75) and after (D125) PrP(Sc) was detected. Affymetrix gene arrays were used to quantify gene expression in the thalamus and Illumina DGE-tag profiling for obex. Ingenuity Pathway Analysis was used to help describe the biological processes of scrapie pathology. Neurological disease and Cancer were common Bio Functions in each tissue at D75; inflammation and cell death were major processes at D125. Several neurological receptors were significantly increased at D75 (e.g. CHRNA6, GRM1, HCN2), which might be clues to the molecular basis of psychiatric changes associated with TSEs. No genes were significantly differentially expressed at both D75 and D125 and there was no progression of events from earlier to later time points. This implies that there is no simple linear progression of pathological or molecular events. There seems to be a step-change between D75 and D125, correlating with the detection of PrP(Sc), resulting in the involvement of different pathological processes in later TSE disease.
Topics: Animals; Brain; Disease Progression; Gene Expression Profiling; Genotype; Microarray Analysis; New Zealand; PrPSc Proteins; Scrapie; Sheep, Domestic; Time Factors; Transcriptome
PubMed: 25183238
DOI: 10.1016/j.vetmic.2014.07.026 -
Veterinary Research Feb 2011Scrapie in sheep and goats has been known for more than 250 years and belongs nowadays to the so-called prion diseases that also include e.g. bovine spongiform...
Scrapie in sheep and goats has been known for more than 250 years and belongs nowadays to the so-called prion diseases that also include e.g. bovine spongiform encephalopathy in cattle (BSE) and Creutzfeldt-Jakob disease in humans. According to the prion hypothesis, the pathological isoform (PrPSc) of the cellular prion protein (PrPc) comprises the essential, if not exclusive, component of the transmissible agent. Currently, two types of scrapie disease are known--classical and atypical/Nor98 scrapie. In the present study we examine 24 cases of classical and 25 cases of atypical/Nor98 scrapie with the sensitive PET blot method and validate the results with conventional immunohistochemistry. The sequential detection of PrPSc aggregates in the CNS of classical scrapie sheep implies that after neuroinvasion a spread from spinal cord and obex to the cerebellum, diencephalon and frontal cortex via the rostral brainstem takes place. We categorize the spread of PrPSc into four stages: the CNS entry stage, the brainstem stage, the cruciate sulcus stage and finally the basal ganglia stage. Such a sequential development of PrPSc was not detectable upon analysis of the present atypical/Nor98 scrapie cases. PrPSc distribution in one case of atypical/Nor98 scrapie in a presumably early disease phase suggests that the spread of PrPSc aggregates starts in the di- or telencephalon. In addition to the spontaneous generation of PrPSc, an uptake of the infectious agent into the brain, that bypasses the brainstem and starts its accumulation in the thalamus, needs to be taken into consideration for atypical/Nor98 scrapie.
Topics: Animals; Blotting, Western; Brain; Germany; Immunoassay; Immunohistochemistry; Lymph Nodes; Norway; Palatine Tonsil; Paraffin Embedding; PrPSc Proteins; Scrapie; Sensitivity and Specificity; Sheep; Spinal Cord
PubMed: 21324114
DOI: 10.1186/1297-9716-42-32 -
Veterinary Research Oct 2016Scrapie and bovine spongiform encephalopathy (BSE) are transmissible spongiform encephalopathies (TSE's) affecting sheep and goats. Susceptibility of goats to scrapie is...
Scrapie and bovine spongiform encephalopathy (BSE) are transmissible spongiform encephalopathies (TSE's) affecting sheep and goats. Susceptibility of goats to scrapie is influenced by polymorphisms of the prion protein gene (PRNP) of the host. Five polymorphisms are associated with reduced susceptibility to TSE's. In the study presented here caprine samples from a scrapie eradication program on Cyprus were genotyped and further characterized using BioRad TeSeE rapid test, histological, immunohistochemical and biochemical methods. In total 42 goats from 20 flocks were necropsied from which 25 goats showed a positive result in the rapid test, a spongiform encephalopathy and an accumulation of pathological prion protein (PrP) in the obex. PrP deposits were demonstrated in the placenta, peripheral nervous and lymphoreticular system. Two animals showed PrP-accumulations in peripheral tissues only. By discriminatory immunoblots a scrapie infection could be confirmed for all cases. Nevertheless, slight deviations in the glycosylation pattern might indicate the presence of different scrapie strains. Furthermore scrapie samples from goats in the current study demonstrated less long term resistance to proteinase K than ovine or caprine BSE control samples. Reduced scrapie susceptibility according to the PRNP genotype was demonstrated (Fishers Exact test, p < 0.05) for the goats with at least one polymorphism (p = 0.023) at the six codons examined and in particular for those with polymorphisms at codon 146 (p = 0.016). This work characterizes scrapie in goats having implications for breeding and surveillance strategies.
Topics: Animals; Cyprus; Female; Goat Diseases; Goats; Prion Diseases; Prion Proteins
PubMed: 27716411
DOI: 10.1186/s13567-016-0379-0 -
AJNR. American Journal of Neuroradiology Nov 2012IIH is a syndrome of elevated intracranial pressure without hydrocephalus, mass, or identifiable cause. Diagnosis is made by clinical presentation, intracranial pressure...
BACKGROUND AND PURPOSE
IIH is a syndrome of elevated intracranial pressure without hydrocephalus, mass, or identifiable cause. Diagnosis is made by clinical presentation, intracranial pressure measurement, and supportive imaging findings. A subset of patients with IIH may have tonsillar ectopia, meeting the criteria for Chiari malformation type I but not responding to surgical decompression for Chiari I. The purpose of this study was to determine the incidence and morphology of cerebellar tonsillar ectopia in patients with IIH.
MATERIALS AND METHODS
Forty-three patients with clinically confirmed IIH and 44 age-matched controls were included. Two neuroradiologists with CAQs reviewed sagittal T1-weighted MRI in a blinded fashion and measured cerebellar tonsil and obex positions relative to the foramen magnum and prepontine cistern width at the level of the midpons.
RESULTS
Nine of 43 patients with IIH and 1/44 controls had cerebellar tonsillar ectopia of ≥5 mm. Five of 9 of patients with IIH with ectopia of ≥5 mm also had a "peglike" tonsil configuration. Patients with IIH had a significantly lower tonsillar position (2.1 ± 2.8 mm) than age-matched controls (0.7 ±1.9 mm, P < .05). The obex position was significantly lower in patients with IIH versus controls (-7.9 mm [above the FM] versus -9.4 mm [above the FM], P < .05). The prepontine width was not significantly different between the groups.
CONCLUSIONS
Cerebellar tonsil position in patients with IIH was significantly lower than that in age-matched controls, often times peglike, mimicking Chiari I. A significantly lower obex position suggests an inferiorly displaced brain stem and cerebellum. When tonsillar ectopia of >5 mm is identified, imaging and clinical consideration of IIH are warranted to avoid misdiagnosis as Chiari I.
Topics: Adolescent; Adult; Arnold-Chiari Malformation; Diagnosis, Differential; Georgia; Humans; Incidence; Magnetic Resonance Imaging; Middle Aged; Pseudotumor Cerebri; Reproducibility of Results; Sensitivity and Specificity; Young Adult
PubMed: 22723059
DOI: 10.3174/ajnr.A3068