The growth and developmental of the myodural bridge and its associated structures in the human fetus.

Myodural bridge (MDB) is a dense connective tissue between suboccipital muscle and dura mater. However, there are few reports on the development and maturation of the human MDB. This study aims to explore the developmental relationship between suboccipital muscle and MDB. 30 head and neck specimens from human fetuses (F) ranging from the 12th to 41st week (W) were made into histological sections. The F12W sections showed evidence that the dura mater dominated by fibroblasts, attached to the posterior atlanto-axial membrane (PAAM) which completely sealed the atlanto-axial space. In the F13W stage, myofibrils of the suboccipital muscle fibers increased significantly in number. At the F14W stage, a gap was observed at the caudal end of the PAAM. Numerous myodural bridge-like structures were observed blending into the dura mater through the gap. At the F19W stage, muscle cells mature. Starting at the F21W stage, the MDB were observed as fibroblasts that cross the atlanto-axial interspace and attach to the dura mater. Therefore, the traction generated by the suboccipital muscles seems to promote the maturity of MDB. This study will provide new morphological knowledge to support future research on the function of the human MDB and regulating the development mechanism of MDB.

Low torcular Herophili position and large brainstem-tentorium angle in fetuses with open spinal dysraphism at 11-13 weeks' gestation.

OBJECTIVE: To evaluate whether in fetuses with open spina bifida (OSB) the tentorium can be seen to be displaced downwards and vertically oriented by the time of the 11-13-week scan and whether this is reflected in an alteration of the brainstem-tentorium (BST) angle. METHODS: The study population was recruited between 2015 and 2020 from three fetal medicine referral centers and comprised a control group and a study group of pregnancies with OSB. The control group was recruited prospectively and included singleton pregnancies with a normal sonographic examination after first-trimester combined screening for chromosomal abnormalities and normal outcome. The study group was selected retrospectively and included all cases with OSB between 2015 and 2020. All cases underwent detailed ultrasound assessment at 11 + 0 to 13 + 6 weeks' gestation. The position of the torcular Herophili (TH) was identified in the midsagittal view of the fetal brain with the use of color Doppler and was considered as a proxy for the insertion of the tentorium on the fetal skull. The BST angle was calculated in the same view and was compared between the two groups. RESULTS: Sixty normal fetuses were included in the control group and 22 fetuses with OSB in the study group. In both groups, the BST angle was found to be independent of gestational age or crown-rump length (P = 0.8815, R2 = 0.0003861 in the controls, and P = 0.2665, R2 = 0.00978 in the OSB group). The mean BST angle was 48.7 ± 7.8° in controls and 88.1 ± 1.18°, i.e. close to 90°, in fetuses with OSB. Comparison of BST-angle measurements between the control group and cases with OSB showed a statistically significant difference (P = 0.0153). In all fetuses with OSB, the downward displacement of the TH and tentorium was clearly visible at the 11-13-week scan. CONCLUSIONS: In fetuses with OSB, the BST angle is significantly larger than in normal controls, with the tentorium being almost perpendicular to the brainstem. This sign confirms the inferior displacement of the tentorium cerebelli with respect to its normal insertion on the occipital clivus as early as the first trimester of pregnancy and is useful in the diagnosis of Chiari-II malformation at this early stage. In fetuses with OSB, the low position of the tentorium and TH is clearly visible, even subjectively, at the 11-13-week scan. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

The developing mouse coronal suture at single-cell resolution.

Sutures separate the flat bones of the skull and enable coordinated growth of the brain and overlying cranium. The coronal suture is most commonly fused in monogenic craniosynostosis, yet the unique aspects of its development remain incompletely understood. To uncover the cellular diversity within the murine embryonic coronal suture, we generated single-cell transcriptomes and performed extensive expression validation. We find distinct pre-osteoblast signatures between the bone fronts and periosteum, a ligament-like population above the suture that persists into adulthood, and a chondrogenic-like population in the dura mater underlying the suture. Lineage tracing reveals an embryonic Six2+ osteoprogenitor population that contributes to the postnatal suture mesenchyme, with these progenitors being preferentially affected in a Twist1+/-; Tcf12+/- mouse model of Saethre-Chotzen Syndrome. This single-cell atlas provides a resource for understanding the development of the coronal suture and the mechanisms for its loss in craniosynostosis.

Developmental biology of the meninges.

The meninges are membranous layers surrounding the central nervous system. In the head, the meninges lie between the brain and the skull, and interact closely with both during development. The cranial meninges originate from a mesenchymal sheath on the surface of the developing brain, called primary meninx, and undergo differentiation into three layers with distinct histological characteristics: the dura mater, the arachnoid mater, and the pia mater. While genetic regulation of meningeal development is still poorly understood, mouse mutants and other models with meningeal defects have demonstrated the importance of the meninges to normal development of the calvaria and the brain. For the calvaria, the interactions with the meninges are necessary for the progression of calvarial osteogenesis during early development. In later stages, the meninges control the patterning of the skull and the fate of the sutures. For the brain, the meninges regulate diverse processes including cell survival, cell migration, generation of neurons from progenitors, and vascularization. Also, the meninges serve as a stem cell niche for the brain in the postnatal life. Given these important roles of the meninges, further investigation into the molecular mechanisms underlying meningeal development can provide novel insights into the coordinated development of the head.

Fate of the three embryonic dural sinuses in infants: the primitive tentorial sinus, occipital sinus, and falcine sinus.

PURPOSE: The primitive tentorial, occipital, and falcine sinuses are thought to attain the adult pattern or regress between the fetal stage and adulthood. The anatomy of these three primitive dural sinuses has seldom been studied in the infant population, and it remains unclear when these dural sinuses reach the adult condition. Using computed tomography digital subtraction venography (CT-DSV), we analyzed the anatomy of these embryonic dural sinuses in infants. METHODS: We included 13 infants who underwent CT-DSV prior to neurosurgery and 35 cases with unruptured cerebral aneurysms as normal adult controls. Three embryonic dural sinuses, i.e., the primitive tentorial, occipital, and falcine sinuses, were retrospectively analyzed in CT-DSV images of infants and adults. We also analyzed the drainage patterns of the superficial middle cerebral vein (SMCV), determined by the connection between the primitive tentorial sinus and the cavernous sinus. RESULTS: The primitive tentorial, occipital, and falcine sinuses were present in 15.4%, 46.2%, and none of the infants, respectively, and in 10.0, 8.6, and 2.9% of the adults, respectively. The difference in SMCV draining pattern between infants and adults was insignificant. The incidence of the occipital sinus was significantly higher in infants than in adults. CONCLUSIONS: The connection between the primitive tentorial sinus and the cavernous sinus appears to be established before birth. The occipital sinus is formed at the embryonic stage and mostly regresses after infancy. The falcine sinus is usually obliterated prenatally. Our findings form the basis for interventions by pediatric interventional neuroradiologists and neurosurgeons.

Embryological Consideration of Dural Arteriovenous Fistulas.

The topographical distribution of dural arteriovenous fistulas (DAVFs) was analyzed based on the embryological anatomy of the dural membrane. Sixty-six consecutive cases of intracranial and spinal DAVFs were analyzed based on the angiography, and each shunt point was identified according to the embryological bony structures. The area of dural membranes was categorized into three different groups: a ventral group located on the endochondral bone (VE group), a dorsal group located on the membranous bone (DM group) and a falco-tentorial group (FT group) located in the falx cerebri, tentorium cerebelli, falx cerebelli, and diaphragm sellae. The FT group was designated when the dural membrane was formed only with the dura propria (meningeal layer of the dura mater) and not from the endosteal dura. Cavernous sinus, sigmoid sinus, and anterior condylar confluence was categorized to VE group, which had a female predominance, more benign clinical presentations, and a lower rate of cortical and spinal venous reflux. Transverse sinus, confluence, and superior sagittal sinus belonged to the DM group. Olfactory groove, falx, tent of the cerebellum, and nerve sleeve of spinal cord were categorized to the FT group, which presented later in life and which had a male predominance, more aggressive clinical presentations, and significant cortical and spinal venous reflux. The DAVFs was associated with the layers of the dural membrane characterized by the two different embryological bony structures. The FT group was formed only with the dura propria as an independent risk factor for aggressive clinical course and hemorrhage of DAVFs.

Cranial dural arteriovenous shunts. Part 1. Anatomy and embryology of the bridging and emissary veins.

We reviewed the anatomy and embryology of the bridging and emissary veins aiming to elucidate aspects related to the cranial dural arteriovenous fistulae. Data from relevant articles on the anatomy and embryology of the bridging and emissary veins were identified using one electronic database, supplemented by data from selected reference texts. Persisting fetal pial-arachnoidal veins correspond to the adult bridging veins. Relevant embryologic descriptions are based on the classic scheme of five divisions of the brain (telencephalon, diencephalon, mesencephalon, metencephalon, myelencephalon). Variation in their exact position and the number of bridging veins is the rule and certain locations, particularly that of the anterior cranial fossa and lower posterior cranial fossa are often neglected in prior descriptions. The distal segment of a bridging vein is part of the dural system and can be primarily involved in cranial dural arteriovenous lesions by constituting the actual site of the shunt. The veins in the lamina cribriformis exhibit a bridging-emissary vein pattern similar to the spinal configuration. The emissary veins connect the dural venous system with the extracranial venous system and are often involved in dural arteriovenous lesions. Cranial dural shunts may develop in three distinct areas of the cranial venous system: the dural sinuses and their interfaces with bridging veins and emissary veins. The exact site of the lesion may dictate the arterial feeders and original venous drainage pattern.

Doppler sonographic evaluation of arteriovenous shunt flow in a fetus with dural sinus malformation.

Dural sinus malformation (DSM) is a rare congenital malformation characterized by a dilated dural sinus pouch. We present a case of prenatally diagnosed DSM and propose a parameter to predict poor fetal outcome. Detailed ultrasonography at 26 weeks of our patient showed an intracranial cyst in the left posterior fossa. Color Doppler study indicated an arteriovenous shunt within the cyst with increased blood flow velocity. Based on these findings, fetal DSM with arteriovenous shunt was diagnosed. Because of fetal hydrops with high-output cardiac failure and maternal pregnancy-induced hypertension, labor was induced at 32 weeks and resulted in stillbirth. In conclusion, based on the present case, we can deduce that color Doppler study is useful for prenatal diagnosis of DSM with arteriovenous shunt and that a high-flow velocity to the cystic lesion is a possible predictor of hydropic change in such fetuses.

The intracranial arachnoid mater : a comprehensive review of its history, anatomy, imaging, and pathology.

INTRODUCTION: The arachnoid mater is a delicate and avascular layer that lies in direct contact with the dura and is separated from the pia mater by the cerebrospinal fluid-filled subarachnoid space. The subarachnoid space is divided into cisterns named according to surrounding brain structures. METHODS: The medical literature on this meningeal layer was reviewed in regard to historical aspects, etymology, embryology, histology, and anatomy with special emphasis on the arachnoid cisterns. Cerebrospinal fluid dynamics are discussed along with a section devoted to arachnoid cysts. CONCLUSION: Knowledge on the arachnoid mater and cerebrospinal fluid dynamics has evolved over time and is of great significance to the neurosurgeon in clinical practice.

A quantitative comparison of dura mater tissue structures measured with atomic force microscopy.

BACKGROUND: The growth of a human embryo is a very sophisticated process. Understanding the way it proceeds is a key factor in pathology preventing and treating diseases. Therefore one needs to use advanced to tools and methods to investigate various aspects of the anatomy and physiology of humans during the first months of growth. OBJECTIVES: This work is focused on the structure of dura mater tissue, one of the membranes protecting the brain, which can be responsible for a number of health issues if it develops abnormally. The aim of the work was to observe dura mater tissue structure with atomic force microscopy and to provide a quantitative method of discrimination of both the periosteal and meningeal layers in a 6-month-old human embryo. MATERIAL AND METHODS: The measurements were performed with atomic force microscopy, in air, using tapping mode. The sample was stored in formaldehyde and dried prior to the measurements. RESULTS: The results obtained permitted observation of the structure of the tissue, in particular the presence of collagen fibers. By applying various image analysis tools, quantitative descriptions of both layers were created in order to distinguish them. CONCLUSIONS: The experiment proved that atomic force microscopy can be a useful tool in the investigation of the development process of the dura mater tissue in terms of the appearance of differences related to various functions of the periosteal and meningeal layers.

Developmental changes in human dural innervation.

INTRODUCTION: There is limited published work on the abundant innervation of the human dura mater, its role and responses to injury in humans. The dura not only provides mechanical support for the brain but may also have other functions, including control of the outflow of venous blood from the brain via the dural sinuses. The trigeminal nerve supplies sensory fibres to the dura as well as the leptomeninges, intracranial blood vessels, face, nose and mouth. Its relatively large size in embryonic life suggests an importance in development; the earliest fetal reflexes, mediated by the trigeminal, are seen by 8 weeks. Trigeminal functions vital to the fetus include the coordination of sucking and swallowing and the protective oxygen-conserving reflexes. Like other parts of the nervous system, the trigeminal undergoes pruning and remodelling throughout development. METHODS: We have investigated changes in the innervation of the human dura with age in 27 individuals aged between 31 weeks of gestation and 60 years of postnatal life. Using immunocytochemistry with antibodies to neurofilament, we have found significant changes in the density of dural innervation with age RESULTS: The density of innervation increased between 31 and 40 weeks of gestation, peaking at term and decreasing in the subsequent 3 months, remaining low until the sixth decade. CONCLUSIONS: Our observations are consistent with animal studies but are, to our knowledge, the first to show age-related changes in the density of innervation in the human dura. They provide new insights into the functions of the human dura during development.

The dural sheath of the optic nerve: descriptive anatomy and surgical applications.

The aim of this work was to clarify the descriptive anatomy of the optic dural sheath using microanatomical dissections on cadavers. The orbit is the rostral part of the extradural neural axis compartment; the optic dural sheath forms the central portion of the orbit.In order to describe this specific anatomy, we carefully dissected 5 cadaveric heads (10 orbits) up to the meningeal structure of the orbit and its contents. 1 cadaveric head was reserved for electron microscopy to add to our knowledge of the collagen structure of the optic dural sheath.In this chapter, we describe the anatomy of the interperiostal-dural concept and the anatomy of the orbit. The optic dural sheath contains three portions: the intracranial, the intracanalicular and the intraorbital segment. Each one has specific anatomic relations which result in particular surgical considerations.

Human primitive meninges in and around the mesencephalic flexure and particularly their topographical relation to cranial nerves.

Development of the meninges in and around the plica ventralis encephali has not been well documented. A distinct mesenchymal structure, the so-called plica ventralis encephali, is sandwiched by the fetal mesencephalic flexure. We histologically examined paraffin-embedded sections from 18 human embryos and fetuses at 6-12 weeks of gestation. In the loose tissues of the plica, the first meninx appeared as a narrow membrane along the oculomotor nerve at 7-8 weeks. Subsequently, the plica ventralis evolved into 3 parts: bilateral lateral mesenchymal condensations and a primitive membranous meninx extending between. Notably, the topographical anatomy of the oculomotor, trochlear and trigeminal nerves did not change: the oculomotor nerve ran along the rostral aspect of the membranous meninx, the trigeminal nerve ran along the caudal side of the lateral mesenchymal condensation, and the trochlear nerve remained embedded in the lateral condensation. Up to 9-10 weeks, the lateral mesenchymal condensations became tongue-like folds; i.e., the primitive form of the tentorium cerebelli, while the membranous meninx became the diaphragma sellae. The falx cerebri seemed to develop from the tongue-like folds. Overall, the final tentorium cerebelli corresponded to the regressed plica ventralis, while the parasellar area originated from the base of the plica and other tissues along the ventral aspects of the basisphenoid and basioccipital.

Demonstration of fluid channels in human dura and their relationship to age and intradural bleeding.

PURPOSE: This paper aims to make a systematic study of human dura to establish the presence of fluid transport channels and their relationship to age. METHODS: Samples of parasagittal dura from autopsy cases from mid-gestation to the ninth decade were examined by light microscopy. RESULTS: We have demonstrated the presence of unlined rounded spaces, uncommon in the fetus and neonate but increasingly evident after 30 weeks of postnatal life. We have shown that intradural bleeding is inversely correlated with the presence of these channels and with age. CONCLUSIONS: We suggest that dural maturation, involving the development of arachnoid granulations, may be related to dilatation of intradural fluid channels, allowing them to be identified histologically. The risk of reflux of blood into the dura appears to reduce with age.

Impaired meningeal development in association with apical expansion of calvarial bone osteogenesis in the Foxc1 mutant.

Loss of function of the mouse forkhead/winged helix transcription factor Foxc1 induces congenital hydrocephalus and impaired skull bone development due to failure of apical expansion of the bone. In this study we investigated meningeal development in the congenital hydrocephalus (ch) mouse with spontaneous loss of function mutant of Foxc1, around the period of initiation of skull bone apical expansion. In situ hybridization of Runx2 revealed active apical expansion of the frontal bone begins between embryonic day 13.5 and embryonic day 14.5 in the wild type, whereas expansion was inhibited in the mutant. Ultrastructural analysis revealed that three layers of the meninges begin to develop at E13.5 in the basolateral site of the head and subsequently progress to the apex in wild type. In ch homozygotes, although three layers were recognized at first at the basolateral site, cell morphology and structure of the layers became abnormal except for the pia mater, and arachnoidal and dural cells never differentiated in the apex. We identified meningeal markers for each layer and found that their expression was down-regulated in the mutant arachnoid and dura maters. These results suggest that there is a close association between meningeal development and the apical growth of the skull bones.

Proliferative capacity and osteogenic potential of novel dura mater stem cells on poly-lactic-co-glycolic acid.

The rational design of biomimetic structures for the regeneration of damaged or missing tissue is a fundamental principle of tissue engineering. Multiple variables must be optimized, ranging from the scaffold type to the selection and properties of implanted cell(s). In this study, the osteogenic potential of a novel stem cell was analyzed on biodegradable poly(lactic-co-glycolic acid) (PLGA) biomaterials as a step toward creating new cell-materials constructs for bony regeneration. Dura mater stem cells (DSCs), isolated from rat dura mater, were evaluated and compared to bone marrow stem cells (BMSCs) for proliferative and differentiative properties in vitro. Experiments were carried out on both tissue culture plastic (TCP) and 2D planar films of PLGA. Proliferation of DSCs on both TCP and PLGA films increased over 21 days. Positive fold inductions in all five bone marker genes were observed at days 7, 14, 21 in all experimental samples compared with day 0 controls. DSCs demonstrated greater cell coverage and enhanced matrix staining on 2D PLGA films when compared with BMSCs. These cells can be isolated and expanded in culture and can subsequently attach, proliferate, and differentiate on both TCP and PLGA films to a greater extent than BMSCs. This suggests that DSCs are promising for cell-based bone tissue engineering therapies, particularly those applications involving regeneration of cranial bones.

Differential effects of TGF-beta isoforms on murine fetal dural cells and calvarial osteoblasts.

BACKGROUND: Proteins within the transforming growth factor (TGF)-beta family play a central role in both normal and pathologic calvarial morphogenesis. Previous work has suggested differential functions of the TGF-beta isoforms in these processes. Little is known, however, about effects of TGF-betas on the underlying dura. Furthermore, studies on the effects of TGF-beta isoforms on osteoblasts have been conflicting. The purpose of this study was to determine the effect of TGF-beta isoforms, specifically TGF-beta1 and TGF-beta3, on fetal calvarial osteoblast and dural cell differentiation, proliferation, and apoptosis. METHODS: Primary cultures of fetal calvarial osteoblasts and dural cells were established from embryonic day-18 CD-1 mice. Cells were treated for 48 hours with TGF-beta1 or TGF-beta3. Northern blot analysis, cell counts, and apoptosis assays were performed. RESULTS: In dural cells, TGF-beta1 stimulated the expression of early osteodifferentiation genes and resulted in a slight decrease in cell number and no effect on apoptosis. Similar results were observed in osteoblasts. TGF-beta3 had little or no effect on the genes studied in both cell types but resulted in increased apoptosis and concomitant decreases in cell number in both cell types. CONCLUSIONS: This study demonstrates that dural cells respond to TGF-beta and that this response is isoform-specific. TGF-beta1 stimulates osteodifferentiation of previously uncommitted cells in the dura. It also stimulates early events in bone matrix deposition and has little effect on late markers of bone differentiation in osteoblasts and dural cells. Both isoforms result in decreases in cell number. TGF-beta3 results in greater decreases in cell number and isoform-specific stimulation of apoptosis in both dural cells and calvarial osteoblasts.

Cellular dynamics and tissue interactions of the dura mater during head development.

During development and growth of the neurocranium, the dura mater regulates events in the underlying brain and overlying skull by the release of soluble factors and cellular activity. Morphogenesis of the cranial bones and sutures is dependent on tissue interactions with the dura mater, which control the size and shape of bones as well as sutural patency. Development of the brain also involves interactions with dura mater: secretion of stromal derived factor 1 (SDF-1) is a critical event in directing migration of the external granular layer precursors of the cerebellar cortex and the Cajal-Retzius (CR) cells of the cerebral cortex. The dura mater is also required for growth of the hippocampal dentate gyrus. Wnt1Cre/R26R transgenic reporter mice were used to study the origin and fates of the cells of dura mater during head development. The dura mater of mammals is derived entirely from the cranial neural crest. Beginning around neonatal day 10 (N 10), the dura mater is infiltrated by cells derived from paraxial mesoderm, which later come to predominate. Over the course of infancy, the neural crest-derived cells of the dura mater become sequestered in niche-like distribution characteristic of stem cells. Simultaneously, dura mater cells underlying the sagittal suture migrate upward into the mesodermally-derived mesenchyme separating the parietal bones. Although initially the parietal bones are formed entirely from paraxial mesoderm, the cellular composition gradually becomes chimeric and is populated mainly by neural crest-derived cells by N 30. This occurs as a consequence of osteoblastic differentiation at the dura mater interface and intravasation of neural crest-derived osteoclastic and other hematopoietic precursors. The isolated cells of the dura mater are multipotent in vitro, giving rise to osteoblasts, neuronal cells and other derivatives characteristic of cranial neural crest, possibly reflecting the multipotent nature of dura mater cells in vivo.

TGF-beta2 stimulates cranial suture closure through activation of the Erk-MAPK pathway.

Cranial sutures are important growth sites of the skull. During suture closure, the dura mater is one of the most important sources of various positive and negative regulatory signals. Previous results indicate that TGF-beta2 from dura mater strongly accelerates suture closure, however, its exact regulatory mechanism is still unclear. In this study, we confirmed that removal of dura mater in calvarial organ culture strongly accelerates sagittal suture closure and that this effect is further enhanced by TGF-beta2 treatment. TGF-beta2 stimulated cell proliferation in the MC3T3-E1 cell line. Similarly, it stimulated the proliferation of cells in the sutural space in calvarial organ culture. Furthermore, TGF-beta2-mediated enhanced cell proliferation and suture closure were almost completely inhibited by an Erk-MAPK blocker, PD98059. These results indicate that TGF-beta2-induced activation of Erk-MAPK is an important signaling component that stimulates cell proliferation to enrich osteoprogenitor cells, thereby promoting their differentiation into osteoblasts to achieve a rapid calvarial bone expansion.