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Heliyon Mar 2024Maintaining the integrity of brain barriers is critical for a healthy central nervous system. While extensive research has focused on the blood-brain barrier (BBB) of...
Maintaining the integrity of brain barriers is critical for a healthy central nervous system. While extensive research has focused on the blood-brain barrier (BBB) of the brain vasculature and blood-cerebrospinal fluid barrier (BCSFB) of the choroid plexus, the barriers formed by the meninges have not received as much attention. These membranes create a barrier between the brain and cerebrospinal fluid (CSF), as well as between CSF and blood. Recent studies have revealed that this barrier has been implicated in the development of neurological and immunological disorders. In order to gain a deeper comprehension of the functioning and significance of the meningeal barriers, sophisticated models of these barriers, need to be created. The aim of this paper is to investigate the characteristics of commercially available primary leptomeningeal cells (LMCs) that form the meningeal barriers, in a cultured environment, including their morphology, proteomics, and barrier properties, and to determine whether passaging of these cells affects their behaviour in comparison to their state. The results indicate that higher passage numbers significantly alter the morphology and protein localisation and expression of the LMCs. Furthermore, the primary cell culture co-stained for S100A6 and E-cadherin suggesting it is a co-culture of both pial and arachnoid cells. Additionally, cultured LMCs showed an increase in vimentin and cytokeratin expression and a lack of junctional proteins localisation on the cell membrane, which could suggest loss of epithelial properties due to culture, preventing barrier formation. This study shows that the LMCs may be a co-culture of pial and arachnoid cells, that the optimal LMC passage range is between passages two and five for experimentation and that the primary human LMCs form a weak barrier when in culture.
PubMed: 38434413
DOI: 10.1016/j.heliyon.2024.e26744 -
Scientific Reports Mar 2024Ethical animal use follows the 3R's: Replacement, Reduction and Refinement. Here, we present the use of simultaneous jugular vein and cisterna magna catheterization via...
Ethical animal use follows the 3R's: Replacement, Reduction and Refinement. Here, we present the use of simultaneous jugular vein and cisterna magna catheterization via a port system in rats for repeated fluid sampling for 14 consecutive days without loss of catheter patency. This technique allows repeated intra-animal sampling without anesthesia and, if used with pooling samples from a cohort of animals, replaces the need for terminal collections for sufficient sample volumes.
Topics: Humans; Rats; Animals; Cisterna Magna; Catheterization; Anesthesia; Specimen Handling; Catheters; Cerebrospinal Fluid
PubMed: 38431711
DOI: 10.1038/s41598-024-55666-6 -
Fluids and Barriers of the CNS Feb 2024Impaired cerebrospinal fluid (CSF) dynamics is involved in the pathophysiology of neurodegenerative diseases of the central nervous system and the optic nerve (ON),...
BACKGROUND
Impaired cerebrospinal fluid (CSF) dynamics is involved in the pathophysiology of neurodegenerative diseases of the central nervous system and the optic nerve (ON), including Alzheimer's and Parkinson's disease, as well as frontotemporal dementia. The smallness and intricate architecture of the optic nerve subarachnoid space (ONSAS) hamper accurate measurements of CSF dynamics in this space, and effects of geometrical changes due to pathophysiological processes remain unclear. The aim of this study is to investigate CSF dynamics and its response to structural alterations of the ONSAS, from first principles, with supercomputers.
METHODS
Large-scale in-silico investigations were performed by means of computational fluid dynamics (CFD) analysis. High-order direct numerical simulations (DNS) have been carried out on ONSAS geometry at a resolution of 1.625 μm/pixel. Morphological changes on the ONSAS microstructure have been examined in relation to CSF pressure gradient (CSFPG) and wall strain rate, a quantitative proxy for mass transfer of solutes.
RESULTS
A physiological flow speed of 0.5 mm/s is achieved by imposing a hydrostatic pressure gradient of 0.37-0.67 Pa/mm across the ONSAS structure. At constant volumetric rate, the relationship between pressure gradient and CSF-accessible volume is well captured by an exponential curve. The ONSAS microstructure exhibits superior mass transfer compared to other geometrical shapes considered. An ONSAS featuring no microstructure displays a threefold smaller surface area, and a 17-fold decrease in mass transfer rate. Moreover, ONSAS trabeculae seem key players in mass transfer.
CONCLUSIONS
The present analysis suggests that a pressure drop of 0.1-0.2 mmHg over 4 cm is sufficient to steadily drive CSF through the entire subarachnoid space. Despite low hydraulic resistance, great heterogeneity in flow speeds puts certain areas of the ONSAS at risk of stagnation. Alterations of the ONSAS architecture aimed at mimicking pathological conditions highlight direct relationships between CSF volume and drainage capability. Compared to the morphological manipulations considered herein, the original ONSAS architecture seems optimized towards providing maximum mass transfer across a wide range of pressure gradients and volumetric rates, with emphasis on trabecular structures. This might shed light on pathophysiological processes leading to damage associated with insufficient CSF flow in patients with optic nerve compartment syndrome.
Topics: Humans; Hydrodynamics; Intraocular Pressure; Optic Nerve; Subarachnoid Space; Cerebrospinal Fluid Pressure; Cerebrospinal Fluid
PubMed: 38419077
DOI: 10.1186/s12987-024-00518-8 -
Cureus Jan 2024Recently, there has been a rise in reports of posterior reversible encephalopathy syndrome (PRES), which is an uncommon neurologic illness. The precise cause of PRES...
Recently, there has been a rise in reports of posterior reversible encephalopathy syndrome (PRES), which is an uncommon neurologic illness. The precise cause of PRES syndrome is yet unknown, but there are certain illnesses that have been associated with it. Furthermore, because of advances in imaging methods and growing awareness, the connection between PRES and pre-eclampsia/eclampsia is becoming increasingly recognised. Pre-eclampsia/eclampsia by itself poses distinct perioperative difficulties; in addition, PRES makes anesthesia administration more difficult. Regretfully, there is a lack of knowledge regarding the anesthetic treatment provided to the extremely sick and medically complex patients, and it is uncertain whether the chosen anesthetic might exacerbate neurologic problems. Here, we discuss the implications for the anesthetic management of PRES presentations.
PubMed: 38414675
DOI: 10.7759/cureus.53079 -
International Journal of Surgery Case... Mar 2024Intracranial glioependymal cysts are an uncommon type of neuroepithelial cyst and are encountered much less frequently than arachnoid cysts. These cysts primarily...
INTRODUCTION AND IMPORTANCE
Intracranial glioependymal cysts are an uncommon type of neuroepithelial cyst and are encountered much less frequently than arachnoid cysts. These cysts primarily manifest within the parenchyma of the brain, although exceedingly rare instances have been reported in the lateral ventricles.
CASE PRESENTATION
We present a highly unusual case of a glioependymal cyst in a 7-year-old girl. The glioependymal cyst was located in the midline in the suprasellar region and extended to the upper clivus region. Its only manifestation was precocious puberty. We performed endoscopic fenestration of the cyst, leading to a return of hormonal levels to normal and a slight reduction in cyst size.
CLINICAL DISCUSSION
A comprehensive search of the Medline database revealed only a few documented cases of glioependymal cysts (fewer than 30 cases). Remarkably, the majority (if not all) were located laterally rather than in the midline of the brain. Endoscopic fenestration and biopsy are effective and confirm the diagnosis.
CONCLUSION
This instance of a rare glioependymal cyst located in the midline, spanning the suprasellar and retrosellar regions, is an uncommon occurrence. Its sole presentation was precocious puberty. The successful management of this condition was achieved through an endoscopic approach, leading to the normalization of endocrine abnormalities.
PubMed: 38387370
DOI: 10.1016/j.ijscr.2024.109360 -
Child's Nervous System : ChNS :... May 2024Pulsatile CSF flow patterns include flow through the ventricles to the subarachnoid space and cisterns and from the infra- to the supratentorial subarachnoid space. In...
OBJECTIVE
Pulsatile CSF flow patterns include flow through the ventricles to the subarachnoid space and cisterns and from the infra- to the supratentorial subarachnoid space. In this study, we demonstrate how an obstruction at the level of the prepontine space may lead to obstructive hydrocephalus with specific radiological characteristics, as well as the implications for treatment options.
METHODS
We retrospectively collected data of patients who underwent surgery between February 2010 and December 2022 for hydrocephalus secondary to a suspected prepontine block. One additional patient diagnosed with prepontine block who did not undergo surgery was also included. We excluded patients with a background of previous unrelated neurosurgical procedures or CNS infections.
RESULTS
Six children and two adults were included. Three presented with hydrocephalus on imaging, without any other underlying pathology. Five had a suprasellar arachnoid cyst, with its lower border abating the pons and occluding the spinal subarachnoid space (SAS). All cases had an open aqueduct on T2 sagittal sequences, as well as an infracerebellar or retrocerebellar CSF collection. In most cases, a horizontal web was identified in the prepontine region. Seven cases were treated with an endoscopic fenestration. One patient subsequently underwent a shunt surgery. All the operated children reached normal developmental milestones after surgery.
CONCLUSIONS
This paper describes a rather small series of cases where clear obstruction was observed at the level of the prepontine subarachnoid space. We believe this anatomical subtlety adds to a better understanding of CSF pathways and the role of ETV in treating hydrocephalus, focusing on a small subgroup of patients without a clear obstruction.
Topics: Child; Adult; Humans; Retrospective Studies; Treatment Outcome; Hydrocephalus; Cerebral Ventricles; Cerebral Aqueduct; Ventriculostomy
PubMed: 38376529
DOI: 10.1007/s00381-024-06323-w -
Fluids and Barriers of the CNS Feb 2024Peri-sinus structures such as arachnoid granulations (AG) and the parasagittal dural (PSD) space have gained much recent attention as sites of cerebral spinal fluid...
BACKGROUND
Peri-sinus structures such as arachnoid granulations (AG) and the parasagittal dural (PSD) space have gained much recent attention as sites of cerebral spinal fluid (CSF) egress and neuroimmune surveillance. Neurofluid circulation dysfunction may manifest as morphological changes in these structures, however, automated quantification of these structures is not possible and rather characterization often requires exogenous contrast agents and manual delineation.
METHODS
We propose a deep learning architecture to automatically delineate the peri-sinus space (e.g., PSD and intravenous AG structures) using two cascaded 3D fully convolutional neural networks applied to submillimeter 3D T-weighted non-contrasted MRI images, which can be routinely acquired on all major MRI scanner vendors. The method was evaluated through comparison with gold-standard manual tracing from a neuroradiologist (n = 80; age range = 11-83 years) and subsequently applied in healthy participants (n = 1,872; age range = 5-100 years), using data from the Human Connectome Project, to provide exemplar metrics across the lifespan. Dice-Sørensen and a generalized linear model was used to assess PSD and AG changes across the human lifespan using quadratic restricted splines, incorporating age and sex as covariates.
RESULTS
Findings demonstrate that the PSD and AG volumes can be segmented using T-weighted MRI with a Dice-Sørensen coefficient and accuracy of 80.7 and 74.6, respectively. Across the lifespan, we observed that total PSD volume increases with age with a linear interaction of gender and age equal to 0.9 cm per year (p < 0.001). Similar trends were observed in the frontal and parietal, but not occipital, PSD. An increase in AG volume was observed in the third to sixth decades of life, with a linear effect of age equal to 0.64 mm per year (p < 0.001) for total AG volume and 0.54 mm (p < 0.001) for maximum AG volume.
CONCLUSIONS
A tool that can be applied to quantify PSD and AG volumes from commonly acquired T-weighted MRI scans is reported and exemplar volumetric ranges of these structures are provided, which should provide an exemplar for studies of neurofluid circulation dysfunction. Software and training data are made freely available online ( https://github.com/hettk/spesis ).
Topics: Adult; Humans; Child; Adolescent; Young Adult; Middle Aged; Aged; Aged, 80 and over; Child, Preschool; Longevity; Deep Learning; Magnetic Resonance Imaging; Neural Networks, Computer; Magnetic Resonance Spectroscopy; Image Processing, Computer-Assisted
PubMed: 38350930
DOI: 10.1186/s12987-024-00516-w -
Molecular Genetics & Genomic Medicine Feb 2024Intellectual disability (ID) refers to a childhood-onset neurodevelopmental disorder with a prevalence of approximately 1%-3%.
BACKGROUND
Intellectual disability (ID) refers to a childhood-onset neurodevelopmental disorder with a prevalence of approximately 1%-3%.
METHODS
We performed whole exome sequencing for the patient with ID. And the splicing variant we found was validated by minigene assay.
RESULTS
Here, we report a boy with ID caused by a variant of CNKSR2. His neurological examination revealed hypsarrhythmia via electroencephalography and a right temporal polar arachnoid cyst via brain magnetic resonance imaging. A novel splicing variant in the CNKSR2 gene (NM_014927.5, c.1657+1G>A) was discovered by exome sequencing. The variant caused a 166 bp intron retention between exons 14 and 15, which was validated by a minigene assay. The variant was not reported in public databases such as gnomAD and the Exome Aggregation Consortium.
CONCLUSIONS
The variant was predicted to be damaging to correct the translation of the CNKRS2 protein and was classified as likely pathogenic according to the ACMG guidelines.
Topics: Male; Child; Humans; Developmental Disabilities; Mental Retardation, X-Linked; Intellectual Disability; RNA Splicing; Neurodevelopmental Disorders; Adaptor Proteins, Signal Transducing
PubMed: 38337158
DOI: 10.1002/mgg3.2389 -
PloS One 2024Atlanto-axial instability is a common disease that affects toy-breed dogs. Most cases of atlanto-axial instability are congenital. Furthermore, patients with...
Atlanto-axial instability is a common disease that affects toy-breed dogs. Most cases of atlanto-axial instability are congenital. Furthermore, patients with atlanto-axial instability are predisposed to other concurrent diseases. Therefore, this study aimed to retrospectively determine the presence of concurrent diseases in cases with atlanto-axial instability using imaging data and analyze the relationship between clinical parameters and the incidence of complex malformations. The clinical data and imaging findings of 41 toy-breed dogs diagnosed with atlanto-axial instability were analyzed using their medical records and imaging data. Occipital dysplasia (17/27), atlanto-occipital overlapping (22/34), dens dysplasia (27/41), Chiari-like malformation (8/34), syringomyelia (5/34), lateral ventricular enlargement (20/36), and intracranial arachnoid cyst (5/35) were observed in patients with atlanto-axial instability. The body weight of the patients in the groups with atlanto-occipital overlapping and lateral ventricular enlargement was lower than that of those in the groups without these diseases (1.78 ± 0.71 vs 2.71 ± 1.15 kg, P = 0.0269, 1.60 ± 0.40 vs 2.75 ± 1.08 kg, P = 0.001, respectively). Furthermore, when the correlation between the total number of concurrent diseases and the age at onset and body weight was examined, it became clear that lower body weight was associated with the incidence of a greater number of concurrent diseases. Thus, the findings of this study suggest that toy-breed dogs are more likely to present with complex malformations and should be evaluated carefully with additional examinations and treatment methods.
Topics: Humans; Dogs; Animals; Retrospective Studies; Dog Diseases; Syringomyelia; Physical Examination; Body Weight; Atlanto-Axial Joint
PubMed: 38324604
DOI: 10.1371/journal.pone.0293363