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International Journal of Molecular... Jun 2016Aquaporin-11 (AQP11) is an intracellular aquaporin expressed in various tissues, including brain tissues in mammals. While AQP11-deficient mice have developed fatal...
Aquaporin-11 (AQP11) is an intracellular aquaporin expressed in various tissues, including brain tissues in mammals. While AQP11-deficient mice have developed fatal polycystic kidneys at one month old, the role of AQP11 in the brain was not well appreciated. In this study, we examined the AQP11 expression in the mouse brain and the brain phenotype of AQP11-deficient mice. AQP11 messenger ribonucleic acid (mRNA) and protein were expressed in the brain, but much less than in the thymus and kidney. Immunostaining showed that AQP11 was localized at the epithelium of the choroid plexus and at the endothelium of the brain capillary, suggesting that AQP11 may be involved in water transport at the choroid plexus and blood-brain barrier (BBB) in the brain. The expression of AQP4, another brain AQP expressed at the BBB, was decreased by half in AQP11-deficient mice, thereby suggesting the presence of the interaction between AQP11 and AQP4. The brain of AQP11-deficient mice, however, did not show any morphological abnormalities and the function of the BBB was intact. Our findings provide a novel insight into a water transport mechanism mediated by AQPs in the brain, which may lead to a new therapy for brain edema.
Topics: Animals; Aquaporins; Blood-Brain Barrier; Brain; Gene Expression; Gene Expression Regulation, Developmental; Male; Mice; Mice, Knockout; Permeability; Protein Transport; RNA, Messenger
PubMed: 27258268
DOI: 10.3390/ijms17060861 -
Fluids and Barriers of the CNS Jan 2024CSF has long been accepted to circulate throughout the subarachnoid space, which lies between the arachnoid and pia maters of the meninges. How the CSF interacts with...
Postnatal meningeal CSF transport is primarily mediated by the arachnoid and pia maters and is not altered after intraventricular hemorrhage-posthemorrhagic hydrocephalus.
BACKGROUND
CSF has long been accepted to circulate throughout the subarachnoid space, which lies between the arachnoid and pia maters of the meninges. How the CSF interacts with the cellular components of the developing postnatal meninges including the dura, arachnoid, and pia of both the meninges at the surface of the brain and the intracranial meninges, prior to its eventual efflux from the cranium and spine, is less understood. Here, we characterize small and large CSF solute distribution patterns along the intracranial and surface meninges in neonatal rodents and compare our findings to meningeal CSF solute distribution in a rodent model of intraventricular hemorrhage-posthemorrhagic hydrocephalus. We also examine CSF solute interactions with the tela choroidea and its pial invaginations into the choroid plexuses of the lateral, third, and fourth ventricles.
METHODS
1.9-nm gold nanoparticles, 15-nm gold nanoparticles, or 3 kDa Red Dextran Tetramethylrhodamine constituted in aCSF were infused into the right lateral ventricle of P7 rats to track CSF circulation. 10 min post-1.9-nm gold nanoparticle and Red Dextran Tetramethylrhodamine injection and 4 h post-15-nm gold nanoparticle injection, animals were sacrificed and brains harvested for histologic analysis to identify CSF tracer localization in the cranial and spine meninges and choroid plexus. Spinal dura and leptomeninges (arachnoid and pia) wholemounts were also evaluated.
RESULTS
There was significantly less CSF tracer distribution in the dura compared to the arachnoid and pia maters in neonatal rodents. Both small and large CSF tracers were transported intracranially to the arachnoid and pia mater of the perimesencephalic cisterns and tela choroidea, but not the falx cerebri. CSF tracers followed a similar distribution pattern in the spinal meninges. In the choroid plexus, there was large CSF tracer distribution in the apical surface of epithelial cells, and small CSF tracer along the basolateral surface. There were no significant differences in tracer intensity in the intracranial meninges of control vs. intraventricular hemorrhage-posthemorrhagic hydrocephalus (PHH) rodents, indicating preserved meningeal transport in the setting of PHH.
CONCLUSIONS
Differential CSF tracer handling by the meninges suggests that there are distinct roles for CSF handling between the arachnoid-pia and dura maters in the developing brain. Similarly, differences in apical vs. luminal choroid plexus CSF handling may provide insight into particle-size dependent CSF transport at the CSF-choroid plexus border.
Topics: Animals; Rats; Pia Mater; Gold; Metal Nanoparticles; Meninges; Arachnoid; Hydrocephalus; Cerebral Hemorrhage
PubMed: 38191402
DOI: 10.1186/s12987-023-00503-7 -
Anatomical Record (Hoboken, N.J. : 2007) Dec 2022Unlike the usual peripheral nerve, the optic nerve accompanies a thick "dural sheath," a thin "sheath of pia mater" (SPM), and multiple "septa," which divides the nerve...
Unlike the usual peripheral nerve, the optic nerve accompanies a thick "dural sheath," a thin "sheath of pia mater" (SPM), and multiple "septa," which divides the nerve fibers into fascicles. We collected specimens from 25 adult cadavers and 15 fetuses and revisited the histological architecture of the optic and oculomotor nerves. In the optic chiasma, the meningeal layer of the dura joins the pia to form a thick SPM, and the periosteum of the sphenoid is continuous with the dural sheath at the orbital exit of the bony optic canal. The septa appeared as a cluster of irregularly arrayed fibrous plates in the intracranial course near the chiasma. Thus, the septa were not derived from either the SPM or the dural sheath. In the orbit, the central artery of the retina accompanies collagenous fibers from the dural sheath and the SPM to provide the vascular sheath in the optic nerve. These connective tissue configurations were the same between adult and fetal specimens. At the optic disk, the dural sheath and SPM merged with the sclera, whereas the septa appeared to end at the lamina cribrosa. However, in fetuses without lamina cribrosa, the septa extend into the nerve fiber layer of the retina. The SPM and septa showed strong elastin immunoreactivity, in contrast to the absence of reactivity in the sheaths of the oculomotor nerve. Each S100 protein-positive Schwann sheath of the oculomotor nerve was surrounded by collagenous endoneurium. Glial fibrillary acidic protein-positive astrocytes showed a linear arrangement along the septa.
Topics: Adult; Humans; Optic Nerve; Optic Disk; Connective Tissue; Cadaver; Fetus
PubMed: 35358354
DOI: 10.1002/ar.24925 -
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 -
Acta Neurologica Belgica Feb 2021Spinal adhesive arachnoiditis is a rare pathology involving pia mater of the spinal cord and nerve roots. It can potentially lead to disability-many patients end up... (Review)
Review
Spinal adhesive arachnoiditis is a rare pathology involving pia mater of the spinal cord and nerve roots. It can potentially lead to disability-many patients end up wheelchair-bound due to subsequent paraparesis. It is an infrequent but possible cause of lower extremities weakness in patients with a history of spinal surgery, epidural anaesthesia, myelography or spinal tumors. Three patients, one male and two females, admitted to our unit due to paraparesis presented at least one of the above mentioned risk factors. Each of them had a severe course of illness-progressive paresis of lower extremities. All above cases were diagnosed with spinal adhesive arachnoiditis confirmed with Magnetic Resonance Imaging (MRI) scan-the most sensitive and specific diagnostic tool. Despite conservative treatment and intensive rehabilitation none of the presented patients preserved the ability to mobilise independently. Considering spinal adhesive arachnoiditis in patients with paraparesis and history of typical risk factors should be included in clinical diagnostic procedure.
Topics: Adult; Arachnoiditis; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Muscle Weakness; Thoracic Vertebrae; Tissue Adhesions
PubMed: 32833147
DOI: 10.1007/s13760-020-01431-1 -
Annals of Neurology Mar 2018Cortical spreading depression (CSD) has long been implicated in migraine attacks with aura. The process by which CSD, a cortical event that occurs within the blood-brain...
OBJECTIVE
Cortical spreading depression (CSD) has long been implicated in migraine attacks with aura. The process by which CSD, a cortical event that occurs within the blood-brain barrier (BBB), results in nociceptor activation outside the BBB is likely mediated by multiple molecules and cells. The objective of this study was to determine whether CSD activates immune cells inside the BBB (pia), outside the BBB (dura), or in both, and if so, when.
METHODS
Investigating cellular events in the meninges shortly after CSD, we used in vivo two-photon imaging to identify changes in macrophages and dendritic cells (DCs) that reside in the pia, arachnoid, and dura and their anatomical relationship to TRPV1 axons.
RESULTS
We found that activated meningeal macrophages retract their processes and become circular, and that activated meningeal DCs stop migrating. We found that CSD activates pial macrophages instantaneously, pial, subarachnoid, and dural DCs 6-12 minutes later, and dural macrophages 20 minutes later. Dural macrophages and DCs can appear in close proximity to TRPV1-positive axons.
INTERPRETATION
The findings suggest that activation of pial macrophages may be more relevant to cases where aura and migraine begin simultaneously, that activation of dural macrophages may be more relevant to cases where headache begins 20 to 30 minutes after aura, and that activation of dural macrophages may be mediated by activation of migratory DCs in the subarachnoid space and dura. The anatomical relationship between TRPV1-positive meningeal nociceptors, and dural macrophages and DCs supports a role for these immune cells in the modulation of head pain. Ann Neurol 2018;83:508-521.
Topics: Animals; Cortical Spreading Depression; Dendritic Cells; Dura Mater; Female; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Pia Mater; TRPV Cation Channels
PubMed: 29394508
DOI: 10.1002/ana.25169 -
Cancer Reports (Hoboken, N.J.) Aug 2022Prostate cancer is the most prevalent cancer in men. However, leptomeningeal involvement by prostate carcinoma is a rare event.
BACKGROUND
Prostate cancer is the most prevalent cancer in men. However, leptomeningeal involvement by prostate carcinoma is a rare event.
CASE
Here, we report a 69-year-old patient with castration-resistant metastatic prostate cancer who presented with headache and ataxia. Brain MRI revealed a huge invasive interaxial mass at right occipital lobe with diffuse thickening and enhancement of meninges, the arachnoid, and the pia mater, and he was diagnosed with leptomeningeal carcinomatosis. The patient received whole brain radiotherapy.
CONCLUSION
Despite the fact that brain and leptomeningeal metastases are not very common in patients with prostate cancer, signs and symptoms of nervous system disorders should be assessed carefully, and consideration of such unusual metastases must be considered.
Topics: Aged; Arachnoid; Humans; Magnetic Resonance Imaging; Male; Meningeal Carcinomatosis; Pia Mater; Prostatic Neoplasms
PubMed: 34089302
DOI: 10.1002/cnr2.1463 -
Yonsei Medical Journal Oct 2003A relatively rare condition of ossified chronic subdural hematoma (SDH) mimicking cerebral stroke is presented. A 67-year-old man presented with headache, dysphasia, and...
A relatively rare condition of ossified chronic subdural hematoma (SDH) mimicking cerebral stroke is presented. A 67-year-old man presented with headache, dysphasia, and left-sided hemiparesis. Routine skull x-ray showed a huge calcification extending from the frontal to the parietal regions in the right side. CT and MRI scan revealed a huge ossified SDH covering the right hemisphere. Right frontoparietal craniotomy was performed and the ossified SDH was completely removed. Severe adhesion was noticed between the pia mater and the inner surface of the ossified mass. The subdural mass had ossified hard outer and inner rims and a soft central part. The postoperative course was uneventful and 3 months after the operation, the patient was neurologically intact. The authors report the successful treatment of a patient with a huge ossified SDH covering the right hemisphere. Careful dissection and total removal are needed in such symptomatic cases to avoid cortical injury and to improve results.
Topics: Aged; Hematoma, Subdural, Chronic; Humans; Magnetic Resonance Imaging; Male; Ossification, Heterotopic; Tomography, X-Ray Computed
PubMed: 14584111
DOI: 10.3349/ymj.2003.44.5.915 -
JCI Insight Oct 2019Intrathecal (IT) delivery and pharmacology of antisense oligonucleotides (ASOs) for the CNS have been successfully developed to treat spinal muscular atrophy. However,...
Intrathecal (IT) delivery and pharmacology of antisense oligonucleotides (ASOs) for the CNS have been successfully developed to treat spinal muscular atrophy. However, ASO pharmacokinetic (PK) and pharmacodynamic (PD) properties remain poorly understood in the IT compartment. We applied multimodal imaging techniques to elucidate the IT PK and PD of unlabeled, radioactively labeled, or fluorescently labeled ASOs targeting ubiquitously expressed or neuron-specific RNAs. Following lumbar IT bolus injection in rats, all ASOs spread rostrally along the neuraxis, adhered to meninges, and were partially cleared to peripheral lymph nodes and kidneys. Rapid association with the pia and arterial walls preceded passage of ASOs across the glia limitans, along arterial intramural basement membranes, and along white-matter axonal bundles. Several neuronal and glial cell types accumulated ASOs over time, with evidence of probable glial accumulation preceding neuronal uptake. IT doses of anti-GluR1 and anti-Gabra1 ASOs markedly reduced the mRNA and protein levels of their respective neurotransmitter receptor protein targets by 2 weeks and anti-Gabra1 ASOs also reduced binding of the GABAA receptor PET ligand 18F-flumazenil in the brain over 4 weeks. Our multimodal imaging approaches elucidate multiple transport routes underlying the CNS distribution, clearance, and efficacy of IT-dosed ASOs.
Topics: Animals; Arteries; Brain; Flumazenil; GABA-A Receptor Antagonists; Gene Knockdown Techniques; Humans; Injections, Spinal; Intravital Microscopy; Male; Molecular Targeted Therapy; Muscular Atrophy, Spinal; Neuroglia; Neurons; Oligonucleotides, Antisense; Pia Mater; RNA, Messenger; Rats; Receptors, AMPA; Receptors, GABA-A; Single Photon Emission Computed Tomography Computed Tomography; Spatio-Temporal Analysis; Thionucleotides; Tissue Distribution
PubMed: 31619586
DOI: 10.1172/jci.insight.129240 -
Surgical Neurology International 2020Perivascular spaces are interstitial fluid-filled regions located deep to the pia mater. They play roles in lymphatic drainage and the central nervous system...
BACKGROUND
Perivascular spaces are interstitial fluid-filled regions located deep to the pia mater. They play roles in lymphatic drainage and the central nervous system immunological function. When they enlarge, they are referred to as giant tumefactive perivascular spaces. Often misdiagnosed as cystic neoplasms, they require a high degree of clinical suspicion and key radiological features to be accurately diagnosed. We describe an interesting case in which a man presented with worsening headache, subsequently found on neuroimaging to have this phenomenon.
CASE DESCRIPTION
A 32-year-old man with low testosterone presented to the ER for worsening headache, blurred vision, and photophobia. Computed tomography of the brain showed hydrocephalus with follow-up magnetic resonance imaging revealing several enlarged cystic spaces within the brain, concerning for neoplasm. He ultimately left against medical advice before the further evaluation was done. He followed up with a neurosurgeon as an outpatient, where further review showed characteristic features indicative of giant tumefactive perivascular spaces, thus avoiding the need for unnecessary biopsy and potential surgery.
CONCLUSION
Often misdiagnosed as cystic neoplasms, giant tumefactive perivascular spaces are benign processes that can have a broad presentation with the most common finding being a headache. Key radiologic features, including smooth margins, isointensity to cerebrospinal fluid, and lack of postcontrast enhancement, are crucial to diagnosis, preventing unnecessary surgery with increased morbidity.
PubMed: 32754362
DOI: 10.25259/SNI_532_2019