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Prion 2015Prion proteins (PrP(C)) are cell membrane glycoproteins that can be found in many cell types, but specially in neurons. Many studies have suggested PrP(C)'s...
Prion proteins (PrP(C)) are cell membrane glycoproteins that can be found in many cell types, but specially in neurons. Many studies have suggested PrP(C)'s participation in metal transport and cellular protection against stress in the central nervous system (CNS). On the other hand PrP(Sc), the misfolded isoform of PrP(C) and the pathogenic agent in transmissible spongiform encephalopathies (TSE), has been associated with brain metal dyshomeostasis in prion diseases. Thus, changes in metal concentration associated with protein misfolding and aggregation have been reported for human and animal prion diseases, as well as for other neurodegenerative disorders, such as Parkinson's and Alzheimer's disease. The use of metal concentrations in tissues as surrogate markers for early detection of TSEs has been suggested. Studies on the accumulation of metals in free-ranging white-tailed deer have not been conducted. This study established concentrations of copper, iron, manganese, and magnesium in 2 diagnostic tissues used for CWD testing (obex and retropharyngeal lymph nodes (RLN)). We compared these concentrations between tissues and in relation to CWD status. We established reference intervals (RIs) for these metals and explored their ability to discriminate between CWD-positive and CWD-negative animals. Our results indicate that independent of CWD status, white-tailed deer accumulate higher concentrations of Fe, Mn and Mg in RLN than in obex. White-tailed deer infected with CWD accumulated significantly lower concentrations of Mn and Fe than CWD-negative deer. These patterns differed from other species infected with prion diseases. Overlapping values between CWD positive and negative groups indicate that evaluation of these metals in obex and RLN may not be appropriate as a diagnostic tool for CWD infection in white-tailed deer. Because the CWD-negative deer were included in constructing the RIs, high specificities were expected and should be interpreted with caution. Due to the low sensitivity derived from the RIs, we do not recommend using metal concentrations for disease discrimination.
Topics: Animals; Deer; Illinois; Lymph Nodes; Metals; Models, Biological; Sensitivity and Specificity; Wasting Disease, Chronic
PubMed: 25695915
DOI: 10.1080/19336896.2015.1019194 -
Journal of Neurosurgery Mar 2022Although evidence and descriptions of the central canal (CC) along the medulla oblongata and the spinal cord have been provided by several anatomical and radiological...
OBJECTIVE
Although evidence and descriptions of the central canal (CC) along the medulla oblongata and the spinal cord have been provided by several anatomical and radiological studies, a clear picture and assessment of the opening of the CC, or apertura canalis centralis (ACC), into the fourth ventricle is lacking, due to its submillimetric size and hidden position in the calamus scriptorius.
METHODS
The authors reviewed all of their cases in which patients underwent ventricular transaqueductal flexible endoscopic procedures and selected 44 cases in which an inspection of the region of the calamus scriptorius had been performed and was suitable for study inclusion. Patients were divided into different groups, based on the presence or absence of a chronic pathological process involving the fourth ventricle. In each case, the visual appearance of the opening of the CC of the ACC was classified as no evidence (A0), indirect evidence (A1), or clear evidence (A2). Morphometric measurements were inferred from surrounding structures and the size of surgical tools visible in the field.
RESULTS
The opening of the CC could be clearly observed in all cases (A1 4.5%, A2 95.5%). In normal cases, a lanceolate shape along the median sulcus was most frequently found, with an average size of 600 × 250 µm that became rounded and smaller in size in cases of hydrocephalus. The distance between the caudal margin of the ACC and the obex was about 1.8 mm in normal cases, 2.1 mm in cases of obstructive hydrocephalus, and 1 mm in cases of normal pressure hydrocephalus. The two wings of the area postrema, variable in size and shape, were sited just caudal to the opening.
CONCLUSIONS
A flexible scope inserted through the cerebral aqueduct can approach the hidden calamus scriptorius like a pen fits into an inkpot. With this privileged viewpoint, the authors provide for the first time, to their knowledge, a clear and novel vision of the opening of the CC in the fourth ventricle, along with the precise location of this tiny structure compared to other anatomical landmarks in the inferior triangle.
Topics: Cerebral Aqueduct; Fourth Ventricle; Humans; Hydrocephalus; Hydrocephalus, Normal Pressure; Medulla Oblongata; Neuroendoscopy; Ventriculostomy
PubMed: 34388726
DOI: 10.3171/2020.12.JNS203649 -
Journal of Veterinary Diagnostic... Jul 2015The purpose of our study was to describe the progressive accumulation of the abnormal conformer of the prion protein (PrP(CWD)) and spongiform degeneration in a single...
Progressive accumulation of the abnormal conformer of the prion protein and spongiform encephalopathy in the obex of nonsymptomatic and symptomatic Rocky Mountain elk (Cervus elaphus nelsoni) with chronic wasting disease.
The purpose of our study was to describe the progressive accumulation of the abnormal conformer of the prion protein (PrP(CWD)) and spongiform degeneration in a single section of brain stem in Rocky Mountain elk (Cervus elaphus nelsoni) with chronic wasting disease (CWD). A section of obex from 85 CWD-positive elk was scored using the presence and abundance of PrP(CWD) immunoreactivity and spongiform degeneration in 10 nuclear regions and the presence and abundance of PrP(CWD) in 10 axonal tracts, the subependymal area of the fourth ventricle, and the thin subpial astrocytic layer (glial limitans). Data was placed in a formula to generate an overall obex score. Data suggests that PrP(CWD) immunoreactivity and spongiform degeneration has a unique and relatively consistent pattern of progression throughout a section of obex. This scoring technique utilizing a single section of obex may prove useful in future work for estimating the presence and abundance of PrP(CWD) in peripheral tissues and the nervous system in elk with CWD.
Topics: Animals; Brain; Deer; Prion Diseases; Prions; Protein Conformation; Protein Isoforms; Wasting Disease, Chronic
PubMed: 26185123
DOI: 10.1177/1040638715593368 -
Brain Pathology (Zurich, Switzerland) Jan 2021Sudden unexpected death in epilepsy (SUDEP) is mechanistically complex and one probable cause is seizure-related respiratory dysfunction. Medullary respiratory...
Sudden unexpected death in epilepsy (SUDEP) is mechanistically complex and one probable cause is seizure-related respiratory dysfunction. Medullary respiratory regulatory nuclei include the pre-Bötzinger complex (pre-BötC) in the ventrolateral medulla (VLM), the medullary raphé nuclei (MR) and nucleus of solitary tract in the dorsomedial medulla (DMM). The region of the VLM also contains intermingled tyrosine hydroxylase (TH) catecholaminergic neurones which directly project to the pre-BötC and regulate breathing under hypoxic conditions and our aim was to evaluate these neurones in SUDEP cases. In post-mortem cases from three groups [SUDEP (18), epilepsy controls (8) and non-epilepsy controls (16)] serial sections of medulla (obex + 2 to + 13 mm) were immunolabeled for TH. Three regions of interest (ROI) were outlined (VLM, DMM and MR) and TH-immunoreactive (TH-IR) neurones were evaluated using automated detection for overall labeling index (neurones and processes) and neuronal densities and compared between groups and relative to obex level. C-fos immunoreactivity was also semi-quantitatively evaluated in these regions. We found no significant difference in the density of TH-IR neurones or labeling index between the groups in all regions. Significantly more TH-IR neurones were present in the DMM region than VLM in non-epilepsy cases only (P < 0.01). Regional variations in TH-IR neurones with obex level were seen in all groups except SUDEP. We also identified occasional TH neurones in the MR region in all groups. There was significantly less c-fos labeling in the VLM and MR in SUDEP than non-epilepsy controls but no difference with epilepsy controls. In conclusion, in this series we found no evidence for alteration of total medullary TH-IR neuronal numbers in SUDEP but noted some differences in their relative distribution in the medulla and c-fos neurones compared to control groups which may be relevant to the mechanism of death.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Infant; Male; Medulla Oblongata; Middle Aged; Neurons; Sudden Unexpected Death in Epilepsy; Tyrosine 3-Monooxygenase; Young Adult
PubMed: 32852867
DOI: 10.1111/bpa.12891 -
Child's Nervous System : ChNS :... Oct 2015Modern understanding of the relation between the mutated cancer stem cell and its site of origin and of its interaction with the tissue environment is enhancing the... (Review)
Review
INTRODUCTION
Modern understanding of the relation between the mutated cancer stem cell and its site of origin and of its interaction with the tissue environment is enhancing the importance of developmental anatomy in the diagnostic assessment of posterior fossa tumors in children. The aim of this review is to show how MR imaging can improve on the exact identification of the tumors in the brainstem and in the vicinity of the fourth ventricle in children, using both structural imaging data and a precise topographical assessment guided by the developmental anatomy.
RESULTS
The development of the hindbrain results from complex processes of brainstem segmentation, ventro-dorsal patterning, multiple germinative zones, and diverse migration pathways of the neural progenitors. Depending on their origin in the brainstem, gliomas may be infiltrative or not, as well as overwhelmingly malignant (pons), or mostly benign (cervicomedullary, medullo-pontine tegmental, gliomas of the cerebellar peduncles). In the vicinity of the fourth ventricles, the prognosis of the medulloblastomas (MB) correlates the molecular subtyping as well as the site of origin: WNT MB develop from the Wnt-expressing lower rhombic lip and have a good prognosis; SHH MB develop from the Shh-modulated cerebellar cortex with an intermediate prognosis (dependent on age); recurrences are local mostly. The poor prognosis group 3 MB is radiologically heterogeneous: some tumors present classic features but are juxtaventricular (rather than intraventricular); others have highly malignant features with a small principal tumor and an early dissemination. Group 4 MB has classic features, but characteristically usually does not enhance; dissemination is common. Although there is as yet no clear molecular subgrouping of the ependymomas, their sites of origin and their development can be clearly categorized, as most develop in an exophytic way from the ventricular surface of the medulla in clearly specific locations: the obex region with expansion in the cistern magna, or the lateral recess region with expansion in the CPA and prepontine cisterns (cerebellar ependymomas, and still more intra-brainstem ependymomas are rare). Finally, almost all cerebellar gliomas are pilocytic astrocytomas.
CONCLUSIONS
A developmental and anatomic approach to the posterior fossa tumors in children (together with diffusion imaging data) provides a reliable pre-surgical identification of the tumor and of its aggressiveness.
Topics: Child; Cranial Fossa, Posterior; Diagnostic Imaging; Ependymoma; Glioma; Humans; Infratentorial Neoplasms; Medulloblastoma
PubMed: 26351220
DOI: 10.1007/s00381-015-2834-z -
Frontiers in Neuroanatomy 2022Despite recent improvements in diffusion-weighted imaging, spinal cord tractography is not used in routine clinical practice because of difficulties in reconstructing...
Despite recent improvements in diffusion-weighted imaging, spinal cord tractography is not used in routine clinical practice because of difficulties in reconstructing tractograms, with a pertinent tri-dimensional-rendering, in a long post-processing time. We propose a new full tractography approach to the cervical spinal cord without extensive manual filtering or multiple regions of interest seeding that could help neurosurgeons manage various spinal cord disorders. Four healthy volunteers and two patients with either cervical intramedullary tumors or spinal cord injuries were included. Diffusion-weighted images of the cervical spinal cord were acquired using a Philips 3 Tesla machine, 32 diffusion directions, 1,000 s/mm -value, 2 × 2 × 2 mm voxel size, reduced field-of-view (ZOOM), with two opposing phase-encoding directions. Distortion corrections were then achieved using the FSL software package, and tracking of the full cervical spinal cord was performed using the DSI Studio software (quantitative anisotropy-based deterministic algorithm). A unique region of avoidance was used to exclude everything that is not of the nervous system. Fiber tracking parameters used adaptative fractional anisotropy from 0.015 to 0.045, fiber length from 10 to 1,000 mm, and angular threshold of 90°. In all participants, a full cervical cord tractography was performed from the medulla to the C7 spine level. On a ventral view, the junction between the medulla and spinal cord was identified with its pyramidal bulging, and by an invagination corresponding to the median ventral sulcus. On a dorsal view, the fourth ventricle-superior, middle, and inferior cerebellar peduncles-was seen, as well as its floor and the obex; and gracile and cuneate tracts were recognized on each side of the dorsal median sulcus. In the case of the intramedullary tumor or spinal cord injury, the spinal tracts were seen to be displaced, and this helped to adjust the neurosurgical strategy. This new full tractography approach simplifies the tractography pipeline and provides a reliable 3D-rendering of the spinal cord that could help to adjust the neurosurgical strategy.
PubMed: 36237419
DOI: 10.3389/fnana.2022.993464 -
Brain : a Journal of Neurology Jun 2018Sudden unexpected death in epilepsy (SUDEP) is a leading cause of premature death in patients with epilepsy. One hypothesis proposes that sudden death is mediated by...
Sudden unexpected death in epilepsy (SUDEP) is a leading cause of premature death in patients with epilepsy. One hypothesis proposes that sudden death is mediated by post-ictal central respiratory depression, which could relate to underlying pathology in key respiratory nuclei and/or their neuromodulators. Our aim was to investigate neuronal populations in the ventrolateral medulla (which includes the putative human pre-Bötzinger complex) and the medullary raphe. Forty brainstems were studied comprising four groups: 14 SUDEP, six epilepsy controls, seven Dravet syndrome cases and 13 non-epilepsy controls. Serial sections through the medulla (from obex 1 to 10 mm) were stained for Nissl, somatostatin, neurokinin 1 receptor (for pre-Bötzinger complex neurons) and galanin, tryptophan hydroxylase and serotonin transporter (neuromodulatory systems). Using stereology total neuronal number and densities, with respect to obex level, were measured. Whole slide scanning image analysis was used to quantify immunolabelling indices as well as co-localization between markers. Significant findings included reduction in somatostatin neurons and neurokinin 1 receptor labelling in the ventrolateral medulla in sudden death in epilepsy compared to controls (P < 0.05). Galanin and tryptophan hydroxylase labelling was also reduced in sudden death cases and more significantly in the ventrolateral medulla region than the raphe (P < 0.005 and P < 0.05). With serotonin transporter, reduction in labelling in cases of sudden death in epilepsy was noted only in the raphe (P ≤ 0.01); however, co-localization with tryptophan hydroxylase was significantly reduced in the ventrolateral medulla. Epilepsy controls and cases with Dravet syndrome showed less significant alterations with differences from non-epilepsy controls noted only for somatostatin in the ventrolateral medulla (P < 0.05). Variations in labelling with respect to obex level were noted of potential relevance to the rostro-caudal organization of respiratory nuclear groups, including tryptophan hydroxylase, where the greatest statistical difference noted between all epilepsy cases and controls was at obex 9-10 mm (P = 0.034), the putative level of the pre-Bötzinger complex. Furthermore, there was evidence for variation with duration of epilepsy for somatostatin and neurokinin 1 receptor. Our findings suggest alteration to neuronal populations in the medulla in SUDEP with evidence for greater reduction in neuromodulatory neuropeptidergic and mono-aminergic systems, including for galanin, and serotonin. Other nuclei need to be investigated to evaluate if this is part of more widespread brainstem pathology. Our findings could be a result of previous seizures and may represent a pathological risk factor for SUDEP through impaired respiratory homeostasis during a seizure.
Topics: Adolescent; Adult; Autopsy; Death, Sudden; Epilepsy; Female; Humans; Magnetic Resonance Imaging; Male; Medulla Oblongata; Membrane Proteins; Middle Aged; Nerve Tissue Proteins; Raphe Nuclei; Retrospective Studies; Severity of Illness Index; Young Adult
PubMed: 29608654
DOI: 10.1093/brain/awy078 -
Frontiers in Neuroanatomy 2021The human brainstem harbors neuronal aggregates that ensure the maintenance of several vital functions. It also acts as a major relay structure for the neuronal...
The human brainstem harbors neuronal aggregates that ensure the maintenance of several vital functions. It also acts as a major relay structure for the neuronal information that travels between the cerebral cortex, the cerebellum and the spinal cord. As such, this relatively small portion of the human brain houses a multitude of ascending and descending fibers that course among numerous nuclei whose exact boundaries are still uncertain. Such a large number of nuclei and fiber tracts confined to a relatively small and compact brain region imposes upon the brainstem a highly complex cytoarchitectonic organization that still needs to be deciphered. The present work provides a topographic atlas of the human brainstem composed of 45 anatomical plates, each containing a pair of adjacent sections stained with Cresyl Violet and Luxol Fast Blue to help delineating brainstem nuclei and fiber tracts, respectively. The plates, which cover the entire midbrain, pons and medulla oblongata, are composed of equally-spaced sections referenced and aligned parallel to the ponto-mesencephalic junction rather than the fastigium or the obex. This topographic landmark is particularly suitable for neurosurgical interventions aiming at specific nuclei of the mesencephalic tegmentum. In complement, we provide 8 anatomical plates containing adjacent sections stained for choline acetyltransferase and Luxol Fast Blue, taken through the midbrain and the pons. This open access atlas of the human brainstem is intended to assist neuroanatomists, neurosurgeons and neuropathologists in their work.
PubMed: 34483849
DOI: 10.3389/fnana.2021.627656 -
Journal of Veterinary Diagnostic... Jul 2019is a small subshrub that is distributed throughout Brazil and is responsible for lysosomal storage disease and occasional reproductive problems in cattle, goats,...
is a small subshrub that is distributed throughout Brazil and is responsible for lysosomal storage disease and occasional reproductive problems in cattle, goats, equids, sheep, and deer. We describe herein the clinical, epidemiologic, and pathologic features of hydrallantois in 3 cows naturally poisoned by in Rio Grande do Sul State, Brazil. Clinically, all cows had marked abdominal distension and mild ataxia. After natural death or euthanasia, autopsies revealed that the abdominal distension in all 3 cases was caused by severe enlargement of the uterus, which contained 100-120 L of translucent fluid within the allantois, in addition to adventitial placentation. Microscopic evaluation of the placenta revealed marked diffuse edema, sometimes with a myxomatous appearance. Neurons in the cerebellum and obex were swollen, with mild-to-moderate cytoplasmic granular vacuolation. Histochemical examination with lectins ConA, WGA, and sWGA revealed mild-to-marked staining in the cytoplasm of neurons of the cerebellum and medulla at the level of the obex, indicating the occurrence of α-mannosidosis.
Topics: Allantois; Animals; Brain Diseases; Brazil; Cattle; Cattle Diseases; Female; Malvaceae; Plant Poisoning
PubMed: 31122163
DOI: 10.1177/1040638719850610 -
Frontiers in Neuroanatomy 2024Hox genes govern rostro-caudal identity along the developing spinal cord, which has a well-defined division of function between dorsal (sensory) and ventral (motor)...
INTRODUCTION
Hox genes govern rostro-caudal identity along the developing spinal cord, which has a well-defined division of function between dorsal (sensory) and ventral (motor) halves. Here we exploit developmental Hoxb8 expression, normally restricted to the dorsal cord below the obex, to genetically label spinal cord-to-brain ("spinofugal") axons.
METHODS
We crossed two targeted (knock-in) and two non-targeted recombinase-expressing lines (Hoxb8-IRES-Cre and Hoxb8-T2AFlpO; Hoxb8-Cre and Hoxb8-FlpO, respectively) with appropriate tdtomato-expressing reporter strains. Serial sectioning, confocal and superresolution microscopy, as well as light-sheet imaging was used to reveal robust labeling of ascending axons and their terminals in expected and unexpected regions.
RESULTS
This strategy provides unprecedented anatomical detail of ascending spinal tracts anterior to the brainstem, and reveals a previously undescribed decussating tract in the ventral hypothalamus (the spinofugal hypothalamic decussating tract, or shxt). The absence of Hoxb8-suppressing elements led to multiple instances of ectopic reporter expression in Hoxb8-Cre mice (retinal ganglion and vomeronasal axons, anterior thalamic nuclei and their projections to the anterior cingulate and retrosplenial cortices and subiculum, and a population of astrocytes at the cephalic flexure) and Hoxb8-FlpO mice (Cajal-Retzius cells of the dentate gyrus, and mesenchymal cells of the choroid plexus). While targeted transgenic lines were similar in terms of known spinofugal projections, Hoxb8-IRES-Cre reporters had an additional projection to the core of the facial motor nucleus, and more abundant Hoxb8-lineage microglia scattered throughout the brain than Hoxb8-T2A-FlpO (or any other) mice, suggesting dysregulated Hoxb8-driven reporter expression in one or both lines.
DISCUSSION
This work complements structural and connectivity atlases of the mouse central nervous system, and provides a platform upon which their reactions to injury or disease can be studied. Ectopic Hoxb8-driven recombinase expression may also be a useful tool to study structure and function of other cell populations in non-targeted lines.
PubMed: 38817241
DOI: 10.3389/fnana.2024.1400015