Choroid Plexus Of Lateral Ventricle Research Articles

Investigating the Impact of Hydrocephalus on Epiplexus Cells of the Choroid Plexus

Hydrocephalus is characterized by accumulation of cerebrospinal fluid (CSF) in the brain, resulting from over-production, under-absorption, or blockage of the flow of CSF. Current treatments are limited to surgically placed shunts that often require follow-up procedures. The goal of this research group is to understand the mechanisms of hydrocephalus with the aim of finding effective pharmacological treatments. The animal model used exhibits a mutation in the transmembrane 67 (Tmem67) gene. Homozygous recessive animals present with ventriculomegaly at birth and severe hydrocephalus by postnatal day 15 (P15). Experiments in this study compare tissue obtained from wildtype animals and homozygous mutant animals. The choroid plexus (CP) is the main producer of CSF, making it a target structure in hydrocephalus research. It is a branched tissue that includes a stroma with fenestrated capillaries, wrapped by a tightly regulated barrier epithelium. Choroid plexus epithelial cells (CPe) are multiciliated cells that strictly regulate the osmotic balance of CSF. Epiplexus cells are poorly understood immune cells localized on the apical (CSF-facing) side of the CPe. These cells are believed to share functional characteristics with microglia and macrophages. Microglia are the innate immune cells of the central nervous system; a specialized type of glial cell that interact with neurons, and aid in the structure and immunosurveillance of the brain. Macrophages originate from monocytes and reside in most tissues of the body, responding to cellular signals of injury and infection. Macrophages can be found free-roaming in tissues or associated to epithelial cells, known as border-associated macrophages (BAMs). Due to their association with the CPe, epiplexus cells are considered BAMs. Beyond their apparent similarities to other immune cells, little else is known about the properties and functions of epiplexus cells or their interaction with the CPe or CSF, nor if they play a role in the development of hydrocephalus. This study furthers the understanding of epiplexus cells, specifically how they impact, or are impacted by hydrocephalus. Rat pups (P15) were terminally anesthetized, perfused with 1x PBS, and fixed with 4% PFA. In the lateral ventricle CP, we have visualized CPe-associated cells with morphology consistent with epiplexus cells. These cells are labeled with microglial/macrophage/epiplexus cell markers: allograft inflammatory factor1/ionized calcium-binding adaptor molecule 1 (Iba1), macrosialin (CD68), and mannose receptor type C-1 lectin (CD206). Iba1 is thought to play a role in restructuring the actin cytoskeleton in cells of monocyte lineage (macrophages and microglia), resulting in morphological differences across levels of activation. CD68 is a transmembrane protein commonly expressed in macrophages and monocytes, supposedly related to the oxidized low-density lipoprotein (OxLDL) pathway, which is involved in exacerbating oxidative stress. CD206 is a transmembrane protein that may aid in the roles of detecting pathogens, removing proteins, and sending waste through lymphatic system. Confocal analysis combining cell morphology and immunohistochemical labeling will be used to quantify CPe-associated epiplexus cells in wildtype and hydrocephalic animals. The results will be substantiated using quantitative real-time PCR. Funding: United States Department of Defense Congressionally Directed Medical Research Program Award; Hydrocephalus Association. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Deep learning segmentation of the choroid plexus from structural magnetic resonance imaging (MRI): validation and normative ranges across the adult lifespan

BackgroundThe choroid plexus functions as the blood-cerebrospinal fluid (CSF) barrier, plays an important role in CSF production and circulation, and has gained increased attention in light of the recent elucidation of CSF circulation dysfunction in neurodegenerative conditions. However, methods for routinely quantifying choroid plexus volume are suboptimal and require technical improvements and validation. Here, we propose three deep learning models that can segment the choroid plexus from commonly-acquired anatomical MRI data and report performance metrics and changes across the adult lifespan.MethodsFully convolutional neural networks were trained from 3D T1-weighted, 3D T2-weighted, and 2D T2-weighted FLAIR MRI using gold-standard manual segmentations in control and neurodegenerative participants across the lifespan (n = 50; age = 21–85 years). Dice coefficients, 95% Hausdorff distances, and area-under-curve (AUCs) were calculated for each model and compared to segmentations from FreeSurfer using two-tailed Wilcoxon tests (significance criteria: p < 0.05 after false discovery rate multiple comparisons correction). Metrics were regressed against lateral ventricular volume using generalized linear models to assess model performance for varying levels of atrophy. Finally, models were applied to an expanded cohort of adult controls (n = 98; age = 21–89 years) to provide an exemplar of choroid plexus volumetry values across the lifespan.ResultsDeep learning results yielded Dice coefficient = 0.72, Hausdorff distance = 1.97 mm, AUC = 0.87 for T1-weighted MRI, Dice coefficient = 0.72, Hausdorff distance = 2.22 mm, AUC = 0.87 for T2-weighted MRI, and Dice coefficient = 0.74, Hausdorff distance = 1.69 mm, AUC = 0.87 for T2-weighted FLAIR MRI; values did not differ significantly between MRI sequences and were statistically improved compared to current commercially-available algorithms (p < 0.001). The intraclass coefficients were 0.95, 0.95, and 0.96 between T1-weighted and T2-weighted FLAIR, T1-weighted and T2-weighted, and T2-weighted and T2-weighted FLAIR models, respectively. Mean lateral ventricle choroid plexus volume across all participants was 3.20 ± 1.4 cm3; a significant, positive relationship (R2 = 0.54-0.60) was observed between participant age and choroid plexus volume for all MRI sequences (p < 0.001).ConclusionsFindings support comparable performance in choroid plexus delineation between standard, clinically available, non-contrasted anatomical MRI sequences. The software embedding the evaluated models is freely available online and should provide a useful tool for the growing number of studies that desire to quantitatively evaluate choroid plexus structure and function (https://github.com/hettk/chp_seg).

Manual Segmentation of the Human Choroid Plexus Using Brain MRI.

The choroid plexus has been implicated in neurodevelopment and a range of brain disorders. Evidence demonstrates that the choroid plexus is critical for brain maturation, immune/ inflammatory regulation, and behavioral/cognitive functioning. However, current automated neuroimaging segmentation tools are poor at accurately and reliably segmenting the lateral ventricle choroid plexus. Furthermore, there is no existing tool that segments the choroid plexus located in the third and fourth ventricles of the brain. Thus, a protocol delineating how to segment the choroid plexus in the lateral, third, and fourth ventricle is needed to increase the reliability and replicability of studies examining the choroid plexus in neurodevelopmental and brain disorders. This protocol provides detailed steps to create separately labeled files in 3D Slicer for the choroid plexus based on DICOM or NIFTI images. The choroid plexus will be manually segmented using the axial, sagittal, and coronal planes of T1w images making sure to exclude voxels from gray or white matter structures bordering the ventricles. Windowing will be adjusted to assist in the localization of the choroid plexus and its anatomical boundaries. Methods for assessing accuracy and reliability will be demonstrated as part of this protocol. Gold standard segmentation of the choroid plexus using manual delineations can be used to develop better and more reliable automated segmentation tools that can be openly shared to elucidate changes in the choroid plexus across the lifespan and within various brain disorders.

Elmukashfi’s Protocol for Hippocampal Volumetry; 2022

There is a relation between many neuropsychiatric disorders and reduction in hippocampal volume. So, a protocol for researches in this area is highly needed. Study aimed to design and validate a protocol for hippocampal volumetry to facilitate manual segmentation of hippocampus region. It was a comparative study, carried at Diagnostic Imaging Clinic at Elmoalem Hospital; where 65 Sudanese individuals were surveyed in period (December 2021 –April 2022). Data was collected through master sheet for sociodemographic information, 3D magnetic resonance imaging for measuring hippocampus volume, and imaging acquisition. Software for measurements 3D slicer version (4.11) was used, where hippocampus is mapped by delineating its boundaries. Protocol was composed of mapping hippocampus. Mapping hippocampus: identify sagittal view, lateral fissure, temporal horn of lateral ventricle, hippocampus region, temporal and occipital horn of lateral ventricle, choroid plexus of lateral ventricle. Among these slides hippocampus has been delineated. Statistical Computing: Data was analyzed using SPSS version 23. Reliability test was performed by obtaining Cronbach’s alpha. Protocol considered reliable if value of Cronbach’s alpha is close to (+1). P-value ≤ 0.05 was considered statistically significant. Validation of Protocol: Calculation of hippocampus volume is valid as total volume correlates strongly with both right and left measurements (correlation coefficient 0.76 and 0.87 respectively and p-value &lt;0.001). Reliability test was 0.85; which was close to (+1). Conclusion and recommendation: This protocol represents a valid, reliable, and applicable method for measuring hippocampal volume. It could be a step to develop an international standard protocol for hippocampal volumetry.

Is P‐glycoprotein functionally active at the Blood‐CSF Barrier?

The brain is protected from circulating metabolites and xenobiotics by two major barriers: the blood‐brain barrier (BBB) and the blood‐cerebrospinal fluid (CSF) barrier (BCSFB). The drug efflux transporter P‐glycoprotein (P‐gp) is known to be expressed luminally at the BBB where it limits the entry of circulating drugs and toxins into the brain. The BCSFB, formed by the choroid plexus epithelial cells, similarly expresses membrane transporters to mediate solute efflux or influx into the CSF. There are conflicting findings on P‐gp activity at the BCSFB, and limited studies of P‐gp localization posit the transporter is expressed apically or subapically, implying a paradoxical function to mediate a blood‐to‐CSF transport of xenobiotics and endobiotics. The objective of this study is to clarify the localization and function of P‐gp at the BCSFB utilizing a quantitative fluorescence microscopy approach. Calcein‐AM, commonly used to evaluate P‐gp‐mediated efflux, is a permeable, non‐fluorescent P‐gp substrate that is converted by intracellular esterases into calcein, a fluorescent and impermeable compound. Time‐dependent uptake of 250 nM calcein‐AM was performed in lateral ventricle choroid plexus isolated from adult FVB mice, and confocal imaging was utilized to observe the accumulation of calcein formed in the choroid plexus epithelial cells. Image segmentation was performed using ImageJ to individually quantify choroid plexus cell and blood capillary accumulation of calcein. Coincubation with 2 µM elacridar, a potent P‐gp inhibitor, increased accumulation of calcein in the choroid plexus cells by 5.7‐fold and increased blood capillary accumulation by 11.2‐fold, indicating inhibition of apical efflux transport. Our data suggests that that P‐gp is indeed functionally active at the apical, CSF‐facing membrane of the BCSFB. As CSF drug concentrations are frequently used as a surrogate measure of CNS drug exposure, elucidating the functional role of P‐gp at the BCSFB is critical for understanding the interplay of BBB and BCSFB transporters and their impact on CNS pharmacokinetics and pharmacodynamics.

Frequency, shape, and estimated volume of intracranial physiologic calcification in different age groups investigated by brain computed tomography scan: a retrospective study.

Intracranial calcification is referred to calcification of parenchyma and vascular structures in brain which can be physiologic or pathologic. This study was conducted with the purpose of investigating the frequency, location, pattern, dimensions and estimated volume of intracranial physiologic calcification (IPC) by computer tomography in different age groups. In this cross-sectional retrospective study, brain computed tomography scans of 216 patients were analyzed in 9 age groups each containing 24 patients from 2 to 89 years old. Data were analyzed by SPSS software using one way analysis of variance (ANOVA, post hoc Tukey), chi square, and linear regression tests (P≤0.05 was considered significant). Rate of calcification in different areas were as follows: pineal gland (75.0%), habenula (36.4%), pineohabenula (15.0%), right lateral ventricle choroid plexus (RCP) (67.7%), left lateral ventricle choroid plexus (LCP) (62.7%), falx cerebri (26.8%), petroclinoid ligament (13.2%), tentorium cerebelli (6.8%), third ventricle choroid plexus (0.9%), fourth ventricle choroid plexus (2.7%), basal ganglia (0.9%). A significant correlation exists between the presence of calcification in pineal, habenula, RCP, and LCP (P≤0.001). Nodular shape of calcification was dominant (47.9%). Estimated volume of pineal calcification showed increased levels in group 8 (70–79 years old) compared to group 2 (10–19 years old) (P≤0.05). Since the accurate description of radiologic appearance of IPCs (location, shape, and size) accompanied with age and clinical manifestation is of great importance in diagnosis and distinguishing from pathologic calcification—for example in patients with melatonin dysregulation or schizophrenic patients—this study was required.

Modification of gene expression and soluble factor secretion in the lateral ventricle choroid plexus: Analysis of the impacts on the neocortical development

The choroid plexus (ChP) is the center of soluble factor secretion into the cerebrospinal fluid in the central nervous system. It is known that various signaling factors secreted from the ChP are involved in the regulation of brain development and homeostasis. Intriguingly, the size of the ChP was prominently expanded in the brains of primates, including humans, suggesting that the expansion of the ChP contributed to mammalian brain evolution, leading to the acquisition of higher intelligence and cognitive functions. To address this hypothesis, we established transgenic (Tg) systems using regulatory elements that direct expression of candidate genes in the ChP. Overexpression of sonic hedgehog (Shh) in the developing ChP led to the expansion of the ChP with greater arborization. Shh produced in the ChP caused an increase in neural stem cells (NSCs) in the neocortical region, leading to the expansion of ventricles, ventricular zone and neocortical surface area, and neocortical surface folding. These findings suggest that the activation of Shh signaling via its enhanced secretion from the developing ChP contributed to the evolution of the neocortex. Furthermore, we found that Shh produced in the ChP enhanced NSC proliferation in the postnatal Tg brain, demonstrating that our Tg system can be used to estimate the effects of candidate factors secreted from the ChP on various aspects of brain morphogenesis and functions.

Immunohistochemical Characterization of Hepatic Nuclear Factor 4 Alpha Expression in the Choroid Plexus of the lateral and 4th ventricles of adult Male Rat Brain

The choroid plexus (CP) is present in brain ventricles. It is responsible for cerebrospinal fluid (CSF) secretion and various vital functions. Special proteins present in choroidal epithelium play important roles in CSF production and energy metabolism.This study aims to compare between the lateral and fourth ventricles CPs using hepatocyte nuclear factor 4 alpha (HNF4α), metabolism marker, to evaluate the functional activity of this tissue in the two regions.Ten adult male albino rats were used to study the histological features of the CPs and to study the functional activity by quantitative immunohistochemical labeling with HNF4α marker.The CP of the fourth ventricle had more functional activity than the CP of the lateral ventricle. A quantitative assessment of HNF4α using Aperio ImageScope Software Analysis showed that the lateral ventricle CP mean positivity 0.264 ± 0.083 pixel/micron² while the fourth ventricle CP have mean positivity 0.297 ± 0.043 pixel/micron². The immunohistochemical expression of marker in the fourth ventricle CP were significantly, P ≤ 0.05 higher than those in the lateral ventricle at P ≤ 0.05. Immunohistochemical detection of metabolism marker went along with findings of other histological and biochemical studies to define the CP as a highly dynamic structure with regional variations forming a continuum of one entity tissue capable of functional adaptation according to body needs.

Radiological imaging of choroid plexus tumors: Systematic approach toward diagnosing a choroid plexus tumor

Choroid plexus tumors (CPTs) are rare intraventricular tumors comprising approximately 1% of all brain tumors. The common locations are the lateral ventricle (most common location in children), the third and fourth ventricles (most common location in adults), and cerebellopontine angle. Here, we present the case of a 10-month-old child with complaints of fever (99.6F), abnormal eye movements, and bilateral papilledema. Ultrasound cranium of the child revealed a well-defined hyperechoic lesion adjacent to the trigone and occipital horn of the right lateral ventricle. No vascularity could be appreciated on color Doppler. Non-contrast computed tomography of the brain showed a well-defined lobulated mass lesion epicentered at the choroid plexus of the right lateral ventricle which was hyperdense relative to the brain parenchyma with specks of calcification. Contrast-enhanced magnetic resonance imaging showed a solid intensely enhancing lobulated mass lesion with frond-like morphology originating from the choroid plexus of the occipital horn of the right lateral ventricle. Surgical excision of the CPT was done under aseptic conditions. We try to reinforce the ultrasound (USG), CT, and MRI findings of a CPT which ultimately came out to be a choroid plexus papilloma (CPP) on histopathological examination.

Development of the mammalian cortical hem and its derivatives: the choroid plexus, Cajal-Retzius cells and hippocampus.

The dorsal medial region of the developing mammalian telencephalon plays a central role in the patterning of the adjacent brain regions. This review describes the development of this specialized region of the vertebrate brain, called the cortical hem, and the formation of the various cells and structures it gives rise to, including the choroid plexus, Cajal-Retzius cells and the hippocampus. We highlight the ontogenic processes that create these different forebrain derivatives from their shared embryonic origin and discuss the key signalling pathways and molecules that influence the patterning of the cortical hem. These include BMP, Wnt, FGF and Shh signalling pathways acting with Homeobox factors to carve the medial telencephalon into district progenitor regions, which in turn give rise to the choroid plexus, dentate gyrus and hippocampus. We then link the formation of the lateral ventricle choroid plexus with embryonic and postnatal neurogenesis in the hippocampus.

Migrating Lateral Ventricle Choroid Plexus Cyst into the Fourth Ventricle Causing Acute Hydrocephalus

AbstractChoroid plexus cysts consist of abnormal folds of the choroid plexus that typically resolve prior to birth. Rarely, these cysts persist and may cause outflow obstruction of cerebrospinal fluid. In this article, we presented a 5-month-old male child patient who presented with lethargy, vomiting, and a bulging anterior fontanelle. Magnetic resonance imaging showed one large choroid plexus cyst had migrated from the right lateral ventricle through the third ventricle and cerebral aqueduct into the fourth ventricle causing outflow obstruction. The cyst was attached to the lateral ventricle choroid plexus by a pedicle. The cyst was endoscopically retrieved from the fourth ventricle intact and then fenestrated and coagulated along with several other smaller cysts. Histologic examination confirmed the mass was a choroid plexus cyst. The patient did well after surgery and did not require any cerebrospinal fluid diversion. Nine months after surgery, the patient continued to thrive with no neurological deficits. This case is the first we have found in the literature of a lateral ventricular choroid plexus cyst migrating into the fourth ventricle and the youngest of any migrating choroid plexus cyst. Only three other cases of a migrating choroid plexus cyst have been documented and those only migrated into the third ventricle. New imaging advances are making these cysts easier to identify, but may still be missed on routine sequences. High clinical suspicion for these cysts is necessary for correct treatment of this possible cause of hydrocephalus.

Delayed clearance of cerebrospinal fluid tracer from choroid plexus in idiopathic normal pressure hydrocephalus

Impaired clearance of amyloid-β from choroid plexus is one proposed mechanism behind amyloid deposition in Alzheimer's disease. The present study examined whether clearance from choroid plexus of a cerebrospinal fluid tracer, serving as a surrogate marker of a metabolic waste product, is altered in idiopathic normal pressure hydrocephalus (iNPH), one sub-type of dementia. In a prospective observational study of close to healthy individuals (reference cohort; REF) and individuals with iNPH, we performed standardized T1-weighted magnetic resonance imaging scans before and through 24 h after intrathecal administration of a cerebrospinal fluid tracer (the magnetic resonance imaging contrast agent gadobutrol). Changes in normalized T1 signal within the choroid plexus and cerebrospinal fluid of lateral ventricles were quantified using FreeSurfer. The normalized T1 signal increased to maximum within choroid plexus and cerebrospinal fluid of lateral ventricles 6–9 h after intrathecal gadobutrol in both the REF and iNPH cohorts (enrichment phase). Peak difference in normalized T1 signals between REF and iNPH individuals occurred after 24 h (clearance phase). The results gave evidence for gadobutrol resorption from cerebrospinal fluid by choroid plexus, but with delay in iNPH patients. Whether choroid plexus has a role in iNPH pathogenesis in terms of delayed clearance of amyloid-β remains to be shown.

Intraventricular Hemorrhage Induces Rapid Calcium Signaling and Transcriptional Changes in the Developing Choroid Plexus

Abstract INTRODUCTION Intraventricular hemorrhage (IVH) leads to acute hydrocephalus in a subset of preterm infants by unclear mechanisms that potentially include increased cerebrospinal fluid (CSF) production by the choroid plexus (ChP), based on recent work in adult rats (Karimy et al., 2017). The earliest physiologic changes in ChP epithelial cells likely involve calcium signaling, which is a known cellular messenger in other secretory epithelial cell populations. The following experiments utilize rapid calcium imaging to evaluate how calcium signaling is regulated in embryonic ChP explants, and additionally determine specific transcriptional alterations in Vivo. METHODS 1) Calcium imaging of embryonic explants: Lateral ventricle ChP is dissected at embryonic day 14.5 (E14.5) from a conditional transgenic mouse line (FoxJ1-Cre; Gcamp6f). The ChP explants are kept viable with artificial CSF, exposed to focal blood injections, and imaged for calcium responses using epifluorescence and two-photon imaging. 2) Transcriptional analysis in a model of preterm IVH: Quantitative RT-PCR is performed on acutely dissected ChP at 24 and 48 hr, following in utero injection of age-matched blood in the lateral ventricles of individual embryos (E14.5 pregnant CD1 mice). RESULTS Upon exposure to age-matched E14.5 plasma, nearly all ChP epithelial cells rapidly release highly concentrated intracellular calcium followed by a mosaic pattern of recurrent calcium release. Using different conditions of calcium blockade, we identify endoplasmic reticulum storage as the primary source of intracellular calcium release. Expression of NKCC1 (the predominant apical ion co-transporter in the ChP) rises by 24 hr, suggesting increased ChP ion permeability, consistent with prior reports of a CSF hypersecretion phenotype. CONCLUSION IVH causes immediate intracellular calcium release by the ChP epithelia, followed by increased NKCC1 transcription within 24 hr. Together, these data suggest a rapid and dynamic embryonic ChP responsiveness to hemorrhage and contributes to our understanding of IVH-induced hydrocephalus pathophysiology.

Choroid plexus-derived miR-204 regulates the number of quiescent neural stem cells in the adult brain.

Regulation of adult neural stem cell (NSC) number is critical for lifelong neurogenesis. Here, we identified a post-transcriptional control mechanism, centered around the microRNA 204 (miR-204), to control the maintenance of quiescent (q)NSCs. miR-204 regulates a spectrum of transcripts involved in cell cycle regulation, neuronal migration, and differentiation in qNSCs. Importantly, inhibition of miR-204 function reduced the number of qNSCs in the subependymal zone (SEZ) by inducing pre-mature activation and differentiation of NSCs without changing their neurogenic potential. Strikingly, we identified the choroid plexus of the mouse lateral ventricle as the major source of miR-204 that is released into the cerebrospinal fluid to control number of NSCs within the SEZ. Taken together, our results describe a novel mechanism to maintain adult somatic stem cells by a niche-specific miRNA repressing activation and differentiation of stem cells.

Choroid plexus glutathione peroxidases are instrumental in protecting the brain fluid environment from hydroperoxides during postnatal development.

Hydrogen peroxide, released at low physiological concentration, is involved in different cell signaling pathways during brain development. When released at supraphysiological concentrations in brain fluids following an inflammatory, hypoxic, or toxic stress, it can initiate lipid peroxidation, protein, and nucleic acid damage and contribute to long-term neurological impairment associated with perinatal diseases. We found high glutathione peroxidase and glutathione reductase enzymatic activities in both lateral and fourth ventricle choroid plexus tissue isolated from developing rats, in comparison to the cerebral cortex and liver. Consistent with these, a high protein expression of glutathione peroxidases 1 and 4 was observed in choroid plexus epithelial cells, which form the blood-cerebrospinal fluid barrier. Live choroid plexuses isolated from newborn rats were highly efficient in detoxifying H2O2 from mock cerebrospinal fluid, illustrating the capacity of the choroid plexuses to control H2O2 concentration in the ventricular system of the brain. We used a differentiated cellular model of the blood-cerebrospinal fluid barrier coupled to kinetic and inhibition analyses to show that glutathione peroxidases are more potent than catalase to detoxify extracellular H2O2 at concentrations up to 250 µM. The choroidal cells also formed an enzymatic barrier preventing blood-borne hydroperoxides to reach the cerebrospinal fluid. These data point out the choroid plexuses as key structures in the control of hydroperoxide levels in the cerebral fluid environment during development, at a time when the protective glial cell network is still immature. Glutathione peroxidases are the main effectors of this choroidal hydroperoxide inactivation.

Mice Expressing Myc in Neural Precursors Develop Choroid Plexus and Ciliary Body Tumors

Choroid plexus tumors and ciliary body medulloepithelioma are predominantly pediatric neoplasms. Progress in understanding the pathogenesis of these tumors has been hindered by their rarity and lack of models that faithfully recapitulate the disease. Here, we find that endogenous Myc proto-oncogene protein is down-regulated in the forebrain neuroepithelium, whose neural plate border domains give rise to the anterior choroid plexus and ciliary body. To uncover the consequences of persistent Myc expression, MYC expression was forced in multipotent neural precursors (nestin-Cre:Myc), which produced fully penetrant models of choroid plexus carcinoma and ciliary body medulloepithelioma. Nestin-mediated MYC expression in the epithelial cells of choroid plexus leads to the regionalized formation of choroid plexus carcinoma in the posterior domain of the lateral ventricle choroid plexus and the fourth ventricle choroid plexus that is accompanied by loss of multiple cilia, up-regulation of protein biosynthetic machinery, and hydrocephalus. Parallel MYC expression in the ciliary body leads also to up-regulation of protein biosynthetic machinery. Additionally, Myc expression in human choroid plexus tumors increases with aggressiveness of disease. Collectively, our findings expose a select vulnerability of the neuroepithelial lineage to postnatal tumorigenesis and provide a new mouse model for investigating the pathogenesis of these rare pediatric neoplasms.

Prenatal Diagnosis of Choroid Plexus Cyst: What Next?

Fetal choroid plexus cysts (CPC) are often detected on prenatal ultrasounds and pose a need to formulate protocol for management and counseling. A total of 1024 unselected cases between gestational ages 11 and 20 weeks were sonologically screened for CPC in 1-year period. On ultrasound, CPC are seen as sonolucent spaces in the echogenic choroid plexus of lateral ventricles of brain measuring at least 2-3 mm in diameter. Those diagnosed with CPC were subjected to thorough anomaly scan. Prenatal karyotype was offered in cases of associated anomalies. The incidence of CPC is 1% (10/1024) in this study. Associated anomalies were found in 20% (2/10) of cases, which were offered invasive testing for fetal karyotype. All the cases with isolated CPC had good outcome. Isolated CPC with low-risk biochemical screening for aneuploidies are now considered normal variants rather than a pathology, need no invasive testing and carry a good prognosis. CPC associated with other anomalies warrant invasive testing and are more likely to be associated with Trisomy 18.

Thyroxine (T4) Transfer from Blood to Cerebrospinal Fluid in Sheep Isolated Perfused Choroid Plexus: Role of Multidrug Resistance-Associated Proteins and Organic Anion Transporting Polypeptides.

Thyroxine (T4) enters the brain either directly across the blood–brain barrier (BBB) or indirectly via the choroid plexus (CP), which forms the blood–cerebrospinal fluid barrier (B-CSF-B). In this study, using isolated perfused CP of the sheep by single-circulation paired tracer and steady-state techniques, T4 transport mechanisms from blood into lateral ventricle CP has been characterized as the first step in the transfer across the B-CSF-B. After removal of sheep brain, the CPs were perfused with 125I-T4 and 14C-mannitol. Unlabeled T4 was applied during single tracer technique to assess the mode of maximum uptake (Umax) and the net uptake (Unet) on the blood side of the CP. On the other hand, in order to characterize T4 protein transporters, steady-state extraction of 125I-T4 was measured in presence of different inhibitors such as probenecid, verapamil, BCH, or indomethacin. Increasing the concentration of unlabeled-T4 resulted in a significant reduction in Umax%, which was reflected by a complete inhibition of T4 uptake into CP. In fact, the obtained Unet% decreased as the concentration of unlabeled-T4 increased. The addition of probenecid caused a significant inhibition of T4 transport, in comparison to control, reflecting the presence of a carrier mediated process at the basolateral side of the CP and the involvement of multidrug resistance-associated proteins (MRPs: MRP1 and MRP4) and organic anion transporting polypeptides (Oatp1, Oatp2, and Oatp14). Moreover, verapamil, the P-glycoprotein (P-gp) substrate, resulted in ~34% decrease in the net extraction of T4, indicating that MDR1 contributes to T4 entry into CSF. Finally, inhibition in the net extraction of T4 caused by BCH or indomethacin suggests, respectively, a role for amino acid “L” system and MRP1/Oatp1 in mediating T4 transfer. The presence of a carrier-mediated transport mechanism for cellular uptake on the basolateral membrane of the CP, mainly P-gp and Oatp2, would account for the efficient T4 transport from blood to CSF. The current study highlights a carrier-mediated transport mechanism for T4 movement from blood to brain at the basolateral side of B-CSF-B/CP, as an alternative route to BBB.

A Rare Case of Pericallosal-Interhemispheric Lipoma

We are reporting a case of interhemispheric-pericallosal lipoma, associated with bilateral small lateral ventricle choroid plexuses and third ventricle lipoma as well as partial agenesis of splenium of corpus callosum. Presentation in our case does not correspond to existing classification of pericallosal lipoma and as it is very rare, we are presenting it as a case report. Intracranial lipoma itself is a very rare anomaly and account for 0.06% to 0.46%. It represents a group of developmental abnormality of brain parenchyma that occur during embryogenesis, and it is located more frequently (about 50%) in the pericallosal cistern and may extend into one or both lateral ventricles. Pericallosal lipoma can also be associated with varying degree of callosal anomalies.

Age-Dependent Niche Signals from the Choroid Plexus Regulate Adult Neural Stem Cells

Specialized niches support the lifelong maintenance and function of tissue-specific stem cells. Adult neural stem cells in the ventricular-subventricular zone (V-SVZ) contact the cerebrospinal fluid (CSF), which flows through the lateral ventricles. A largely ignored component of the V-SVZ stem cell niche is the lateral ventricle choroid plexus (LVCP), a primary producer of CSF. Here we show that the LVCP, in addition to performing important homeostatic support functions, secretes factors that promote colony formation and proliferation of purified quiescent and activated V-SVZ stem cells and transit-amplifying cells. The functional effect of the LVCP secretome changes throughout the lifespan, with activated neural stem cells being especially sensitive to age-related changes. Transcriptome analysis identified multiple factors that recruit colony formation and highlights novel facets of LVCP function. Thus, the LVCP is a key niche compartment that translates physiological changes into molecular signals directly affecting neural stem cell behavior.