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Journal of Anatomy Mar 2024In humans and most mammals, there is a notch-like portal, the foramen of Luschka (or lateral foramen), which connects the lumen of the fourth ventricle with the subdural...
In humans and most mammals, there is a notch-like portal, the foramen of Luschka (or lateral foramen), which connects the lumen of the fourth ventricle with the subdural space. Gross dissection, light and scanning electron microscopy, and μCT analysis revealed the presence of a foramen of Luschka in the American alligator (Alligator mississippiensis). In this species, the foramen of Luschka is a notch in the dorsolateral wall of the pons immediately caudal to the peduncular base of the cerebellum, near the rostral end of the telovelar membrane over the fourth ventricle. At the foramen of Luschka there was a transition from a superficial pia mater lining to a deep ependymal lining. There was continuity between the lumen of the fourth ventricle and the subdural space, via the foramen of Luschka. This anatomical continuity was further demonstrated by injecting Evans blue into the lateral ventricle which led to extravasation through the foramen of Luschka and pooling of the dye on the lateral surface of the brain. Simultaneous subdural and intraventricular recordings of cerebrospinal fluid (CSF) pressures revealed a stable agreement between the two pressures at rest. Perturbation of the system allowed for static and dynamic differences to develop, which could indicate varying flow patterns of CSF through the foramen of Luschka.
Topics: Animals; Humans; Alligators and Crocodiles; Subdural Space; Cerebellum; Fourth Ventricle; Ependyma; Mammals
PubMed: 37965891
DOI: 10.1111/joa.13972 -
Cureus Sep 2023Leptomeningeal carcinomatosis (LC) is an uncommon sequelae of metastatic cancer affecting the pia and arachnoid mater. It has been postulated that recent improvements...
Leptomeningeal carcinomatosis (LC) is an uncommon sequelae of metastatic cancer affecting the pia and arachnoid mater. It has been postulated that recent improvements in cancer patient survival time have increased the frequency of LC and other rare metastatic conditions that patients previously would not have lived long enough to experience. LC carries a universally poor prognosis with a mean survival of between two to four months if treated; however, the recent increase in incidence has allowed for further research into the condition and potential treatments. Options for administering chemotherapy have been limited in the past, but recent developments in surgical chemotherapeutic ports have allowed for intrathecal delivery of drugs like methotrexate without systemic exposure. In fact, innovative delivery systems undergoing clinical trials can deliver these drugs in a metronomic fashion to limit the leukoencephalopathy complications of methotrexate. Primary breast cancer is the most common source of metastatic leptomeningeal lesions, and such a lesion was observed by the authors in the cadaver of a 70-year-old Caucasian female with unspecified breast cancer in a medical school anatomic laboratory. The cause of death was listed as "complication of malignant neoplasm of unspecified site of unspecified female breast." Through this case report, we seek to develop our understanding of this rare metastatic phenomenon and highlight the importance of student cadaveric dissection.
PubMed: 37790014
DOI: 10.7759/cureus.44533 -
ACS Applied Electronic Materials Sep 2023Printed circuit boards (PCBs) physically support and connect electronic components to the implementation of complex circuits. The most widespread insulating substrate...
Printed circuit boards (PCBs) physically support and connect electronic components to the implementation of complex circuits. The most widespread insulating substrate that also acts as a mechanical support in PCBs is commercially known as FR4, and it is a glass-fiber-reinforced epoxy resin laminate. FR4 has exceptional dielectric, mechanical, and thermal properties. However, it was designed without considering sustainability and end-of-life aspects, heavily contributing to the accumulation of electronic waste in the environment. Thus, greener alternatives that can be reprocessed, reused, biodegraded, or composted at the end of their function are needed. This work presents the development and characterization of a PCB substrate based on poly(lactic acid) and cotton fabric, a compostable alternative to the conventional FR4. The substrate has been developed by compression molding, a process compatible with the polymer industry. We demonstrate that conductive silver ink can be additively printed on the substrate's surface, as its morphology and wettability are similar to those of FR4. For example, the compostable PCB's water contact angle is 72°, close to FR4's contact angle of 64°. The developed substrate can be thermoformed to curved surfaces at low temperatures while preserving the conductivity of the silver tracks. The green substrate has a dielectric constant comparable to that of the standard FR4, showing a value of 5.6 and 4.6 at 10 and 100 kHz, respectively, which is close to the constant value of 4.6 of FR4. The substrate is suitable for microdrilling, a fundamental process for integrating electronic components to the PCB. We implemented a proof-of-principle circuit to control the blinking of LEDs on top of the PCB, comprising resistors, capacitors, LEDs, and a dual in-line package circuit timer. The developed PCB substrate represents a sustainable alternative to standard FR4 and could contribute to the reduction of the overwhelming load of electronic waste in landfills.
PubMed: 37779887
DOI: 10.1021/acsaelm.3c00799 -
Neuron Dec 2023Leptomeninges, consisting of the pia mater and arachnoid, form a connective tissue investment and barrier enclosure of the brain. The exact nature of leptomeningeal...
Leptomeninges, consisting of the pia mater and arachnoid, form a connective tissue investment and barrier enclosure of the brain. The exact nature of leptomeningeal cells has long been debated. In this study, we identify five molecularly distinct fibroblast-like transcriptomes in cerebral leptomeninges; link them to anatomically distinct cell types of the pia, inner arachnoid, outer arachnoid barrier, and dural border layer; and contrast them to a sixth fibroblast-like transcriptome present in the choroid plexus and median eminence. Newly identified transcriptional markers enabled molecular characterization of cell types responsible for adherence of arachnoid layers to one another and for the arachnoid barrier. These markers also proved useful in identifying the molecular features of leptomeningeal development, injury, and repair that were preserved or changed after traumatic brain injury. Together, the findings highlight the value of identifying fibroblast transcriptional subsets and their cellular locations toward advancing the understanding of leptomeningeal physiology and pathology.
Topics: Mice; Animals; Meninges; Arachnoid; Pia Mater; Choroid Plexus; Brain
PubMed: 37776854
DOI: 10.1016/j.neuron.2023.09.002 -
Cells Sep 2023Immune cells play a critical role in promoting neuroinflammation and the development of neuropathic pain. However, some subsets of immune cells are essential for pain...
Immune cells play a critical role in promoting neuroinflammation and the development of neuropathic pain. However, some subsets of immune cells are essential for pain resolution. Among them are regulatory T cells (Tregs), a specialised subpopulation of T cells that limit excessive immune responses and preserve immune homeostasis. In this study, we utilised intrathecal adoptive transfer of activated Tregs in male and female mice after peripheral nerve injury to investigate Treg migration and whether Treg-mediated suppression of pain behaviours is associated with changes in peripheral immune cell populations in lymphoid and meningeal tissues and spinal microglial and astrocyte reactivity and phenotypes. Treatment with Tregs suppressed mechanical pain hypersensitivity and improved changes in exploratory behaviours after chronic constriction injury (CCI) of the sciatic nerve in both male and female mice. The injected Treg cells were detected in the choroid plexus and the pia mater and in peripheral lymphoid organs in both male and female recipient mice. Nonetheless, Treg treatment resulted in differential changes in meningeal and lymph node immune cell profiles in male and female mice. Moreover, in male mice, adoptive transfer of Tregs ameliorated the CCI-induced increase in microglia reactivity and inflammatory phenotypic shift, increasing M2-like phenotypic markers and attenuating astrocyte reactivity and neurotoxic astrocytes. Contrastingly, in CCI female mice, Treg injection increased astrocyte reactivity and neuroprotective astrocytes. These findings show that the adoptive transfer of Tregs modulates meningeal and peripheral immunity, as well as spinal glial populations, and alleviates neuropathic pain, potentially through different mechanisms in males and females.
Topics: Mice; Male; Female; Animals; T-Lymphocytes, Regulatory; Hyperalgesia; Neuralgia; Spinal Cord; Meninges
PubMed: 37759539
DOI: 10.3390/cells12182317 -
Nature Communications Sep 2023Meninges cover the surface of the brain and spinal cord and contribute to protection and immune surveillance of the central nervous system (CNS). How the meningeal...
Meninges cover the surface of the brain and spinal cord and contribute to protection and immune surveillance of the central nervous system (CNS). How the meningeal layers establish CNS compartments with different accessibility to immune cells and immune mediators is, however, not well understood. Here, using 2-photon imaging in female transgenic reporter mice, we describe VE-cadherin at intercellular junctions of arachnoid and pia mater cells that form the leptomeninges and border the subarachnoid space (SAS) filled with cerebrospinal fluid (CSF). VE-cadherin expression also marked a layer of Prox1 cells located within the arachnoid beneath and separate from E-cadherin arachnoid barrier cells. In vivo imaging of the spinal cord and brain in female VE-cadherin-GFP reporter mice allowed for direct observation of accessibility of CSF derived tracers and T cells into the SAS bordered by the arachnoid and pia mater during health and neuroinflammation, and detection of volume changes of the SAS during CNS pathology. Together, the findings identified VE-cadherin as an informative landmark for in vivo imaging of the leptomeninges that can be used to visualize the borders of the SAS and thus potential barrier properties of the leptomeninges in controlling access of immune mediators and immune cells into the CNS during health and neuroinflammation.
Topics: Female; Animals; Mice; Pia Mater; Neuroinflammatory Diseases; Central Nervous System; Arachnoid; Cadherins; Inflammation; Mice, Transgenic
PubMed: 37730744
DOI: 10.1038/s41467-023-41580-4 -
Oncology Letters Oct 2023Central nervous system (CNS) malignant melanomas are rare tumors of the CNS that are thought to arise from aberrant changes in melanocytes of the neural crest or...
Central nervous system (CNS) malignant melanomas are rare tumors of the CNS that are thought to arise from aberrant changes in melanocytes of the neural crest or melanocytic elements of the pia mater during early embryonic development. As a rare type of CNS malignant melanoma, only a few cases of primary malignant melanoma in the spinal canal have been reported thus far. The majority of these studies have reported on the diagnosis, radiographic features and gross total resection of primary spinal canal malignant melanoma; however, the prognosis and ideal treatment of patients with residual tumors remain elusive. The current study presented the rare case of a patient with primary malignant melanoma originating from the thoracic spinal canal, without any history of irradiation exposure and with an incompletely resected tumor. Disease-free survival of >2.5 years was observed in this patient who was treated with concurrent chemoradiotherapy followed by adjuvant chemotherapy with temozolomide and bevacizumab.
PubMed: 37664668
DOI: 10.3892/ol.2023.14020 -
BioRxiv : the Preprint Server For... Aug 2023The recent characterization of the glymphatic system and meningeal lymphatics has re-emphasized the role of the meninges in facilitating CSF transport and clearance....
BACKGROUND
The recent characterization of the glymphatic system and meningeal lymphatics has re-emphasized the role of the meninges in facilitating CSF transport and clearance. Here, we characterize small and large CSF solute distribution patterns along the intracranial and surface meninges in neonatal rodents and compare our findings to a rodent model of intraventricular hemorrhage-posthemorrhagic hydrocephalus. We also examine CSF 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 minutes post-1.9-nm gold nanoparticle and Red Dextran Tetramethylrhodamine injection and 4 hours 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 performed.
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 dura mater of 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 leptomeninges 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.
PubMed: 37645776
DOI: 10.1101/2023.08.10.552826