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.

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.

Anatomic relations of the arachnoidea around the pituitary stalk: relevance for surgical removal of craniopharyngiomas.

PURPOSE: The growth pattern of craniopharyngiomas (CP) is yet to be understood due to challenges arising from the diversity of morphological features that exist. This in turn has had implications on the development of safe surgical strategies for management of these lesions. The aim of this study is to propose a morphological classification of CP based on their tumor-membrane relationship. It is hoped that this will contribute to better understanding of CP morphology and prediction of the intraoperative classification. METHODS: Histological techniques were used to study eight fetuses. Following Masson staining, the membranes around the pituitary stalk were observed under microscope. Pre-operative MRI and intraoperative images of 195 patients with CP were also analyzed. FINDINGS: The arachnoidal sleeve around the pituitary stalk (ASPS) was noted to be comprised of a compact fibrous component and a related loose trabecular component. The pituitary stalk was divided into four segments in accordance with the folds of the ASPS. Correspondingly, the growth of CPs was divided into four basic patterns-infra-diaphragmatic (ID), extra-arachnoidal (EA), intra-arachnoidal (IA) and sub-arachnoidal (SA) growth. The IA growth pattern can be further subdivided into two subtypes-namely, IA1 (with tumor growing within the fibrous component of the ASPS) and IA2 (with tumor growing within the trabecular component). This method of topographical division can be used to understand the growth of CP-infra-diaphragmatic CP show growth pattern ID or ID together with EA. Suprasellar CP can show an extra-ventricular growth pattern (EA or IA2), an extra- and intra-ventricular (IA2 + SA) growth pattern, a trans-infundibular growth pattern (ID + IA1 + SA) and an infundibulo-tuberal growth pattern (SA or SA + IA1). There is a statistically significant difference between CP growth patterns in children and adults. A predominance of ID growth is noted in children while adults tend to show a pattern of predominantly Extra-ventricular (EV) growth. CONCLUSION: Our proposed classification details the relationship of the surrounding structures to CPs and purports to predict and identify the intraoperative anatomical stratification. It also attempts to help predict the growth patterns of these tumors. A knowledge of the intimate relations of the tumor and its key surrounding structures allows for safe surgical removal.

Role of FOXC1 in regulating APSCs self-renewal via STI-1/PrPC signaling.

Forkhead box protein C1 (FOXC1) is known to regulate developmental processes in the skull and brain. Methods: The unique multipotent arachnoid-pia stem cells (APSCs) isolated from human and mouse arachnoid-pia membranes of meninges were grown as 3D spheres and displayed a capacity for self-renewal. Additionally, APSCs also expressed the surface antigens as mesenchymal stem cells. By applying the FOXC1 knockout mice and mouse brain explants, signaling cascade of FOXC1-STI-1-PrPC was investigated to demonstrate the molecular regulatory pathway for APSCs self-renewal. Moreover, APSCs implantation in stroke model was also verified whether neurogenic property of APSCs could repair the ischemic insult of the stroke brain. Results: Activated FOXC1 regulated the proliferation of APSCs in a cell cycle-dependent manner, whereas FOXC1-mediated APSCs self-renewal was abolished in FOXC1 knockout mice (FOXC1-/- mice). Moreover, upregulation of STI-1 regulated by FOXC1 enhanced cell survival and self-renewal of APSCs through autocrine signaling of cellular prion protein (PrPC). Mouse brain explants STI-1 rescues the cortical phenotype in vitro and induces neurogenesis in the FOXC1-/- mouse brain. Furthermore, administration of APSCs in ischemic brain restored the neuroglial microenvironment and improved neurological dysfunction. Conclusion: We identified a novel role for FOXC1 in the direct regulation of the STI-1-PrPC signaling pathway to promote cell proliferation and self-renewal of APSCs.

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.

Causes of arachnoid cyst development and expansion.

Arachnoid cysts are frequent incidental findings on neuroimaging studies and in clinical practice. Theories of their origin, still matter for debate, compose four categories: 1) a ball-valve mechanism; 2) an osmotic gradient between the intra- and extracystic medium; 3) primary malformation of the arachnoid membrane or cerebral lobe agenesis; and 4) fluid hypersecretion by the lining cells of the cyst wall. The cause of cyst enlargement is also debatable, although there is strong controversial evidence supporting the last two theories rather than the former. Brain water homeostasis and its regulatory pathways are weakly understood at the molecular level. In this brief report the authors attempt to add new insights into the pathogenesis of arachnoid cysts by considering aquaporin expression in the cyst wall and discuss possible future research directions and molecular targets.

The meninges in human development.

The brain and cranial meninges were studied in 61 serially sectioned embryos of stages 8-23. Much earlier stages than those examined by previous authors provided a more comprehensive view of meningeal development. As a result, the possible and probable sources of the cranial and spinal meninges are believed to be: (a) prechordal plate, (b) unsegmented paraxial (parachordal) mesoderm, (c) segmented paraxial (somitic) mesoderm, (d) mesectoderm (neural crest), (e) neurilemmal cells (neural crest), and (f) neural tube. Some of these sources (a, b, d) pertain to the cranial meninges, others (c, d, e) to the spinal coverings. The first of the future dural processes to develop is the tentorium cerebelli, which, at the end of the embryonic period proper, differs considerably in shape and composition from the later fetal and postnatal tentorium. The embryonic dural limiting layer (Duragrenzschicht) probably corresponds to the interface layer of the adult meninges. The appropriate literature was reviewed and summarized.

Developmental study of leptomeningeal glioneuronal heterotopia.

The timing of the appearance of leptomeningeal glioneuronal heterotopia (LGH) and its immunohistochemical development were examined on autopsied brains ranging from 12 to 43 weeks of postmenstrual age. LGH appeared at 20 weeks postmenstrual age and its incidence gradually increased until 28-31 weeks. All patients with trisomy 13 who were older than 34 weeks postmenstrual age had LGH. Glial fibrillary acidic protein-positive glial processes appeared earlier in the subpial layer of brainstems in patients with trisomy 13 than in the controls without LGH, and protruded along the perforating vessels into the leptomeninges; therefore, LGH may be formed from the midfetal period and develop with an increase of subpial glial processes along perforating vessels.

The cranial meninges: anatomic considerations.

The anatomy of the cranial dura and leptomeninges is both intricate and complex. A thorough discussion of the protective covering of the brain including the dura, arachnoid, and pia is provided on both gross and microscopic levels. An attempt to include issues of clinical relevance is made, highlighting the Virchow-Robin spaces and the optic sheath. In addition, the normal appearance of the dura and leptomeninges on MRI is presented to establish a framework for the discussion of leptomeningeal pathology.

[Arachnoid cysts: histologic, embryologic and physiopathologic review]. / Les kystes arachnoïdiens : mise au point histologique, embryologique et physio-pathologique.

Arachnoid cysts form a cavity containing a cerebrospinal-like fluid, the wall of which is composed of arachnoidal cells. Other types of intracranial cysts have been described, they differ from arachnoid cysts by the histological characteristics of their wall. To analyze homogeneous series, it is thus necessary to differentiate arachnoid cysts from the other types of cysts. Several localizations of these lesions have been described: the most frequent being the temporo-sylvian area. Arachnoid cysts are considered as resulting from congenital malformations that can change during postnatal life. They can no longer be considered as resulting from cerebral atrophy. This arachnoid malformation could be the primary event or be explained by an impairment of the cerebrospinal fluid drainage generated by venous agenesis. Several mechanisms could account for the inflation of these cysts: secretion by the cells forming the cyst walls, unidirectional valve, liquid movements secondary to pulsations of the veins.

Morphology of the Willis chords in the superior sagittal sinus during various periods of life.

UNLABELLED: Numerous fibrous elements known as the Willis chords are situated in the light of the superior sagittal sinus. The paper is aimed at a comparative evaluation of the appearance of the Willis chords appearing in the superior sagittal sinus during various periods of human life and a determination of their role. The material comprises 200 brains at the foetal period as well as 200 adult and senile brains. The experimental methods include injection methods, infrared light, the Pickworth method and computer image analysis. During adulthood, various elements such as valvulae, divisions, plates, beams and arachnoidal granulation are situated in the light of superior sagittal sinus. The number of arachnoidal granulations increases continuously due to age, new ones appearing close to those already in existence and old granulation spreading. The superior sagittal sinus contains numerous valvulae similar to the feedback flaps typical for hydraulic systems. Divisions act as orifices which lead to a fall in pressure and induce blood into the sinus. Large differences between the cross-sections of meningeal veins and bridge veins were noticed, which resembles the structure of ejector. The blood flow in the bridge veins ending at the superior sagittal sinus is controlled by the valvulae and their geometrical form changes according to age. CONCLUSION: The Willis chords situated in the superior sagittal sinus may control the circulation. Their number grows with age and their morphology changes.

Identification of a progenitor cell of origin capable of generating diverse meningioma histological subtypes.

Meningiomas are among the most common primary central nervous system tumours in adults. Studies focused on the molecular basis for meningioma development are hampered by a lack of information with regard to the cell of origin for these brain tumours. Herein, we identify a prostaglandin D synthase-positive meningeal precursor as the cell of origin for murine meningioma, and show that neurofibromatosis type 2 (Nf2) inactivation in prostaglandin D2 synthase (PGDS) (+) primordial meningeal cells, before the formation of the three meningeal layers, accounts for the heterogeneity of meningioma histological subtypes. Using a unique PGDSCre strain, we define a critical embryonic and early postnatal developmental window in which biallelic Nf2 inactivation in PGDS (+) progenitor cells results in meningioma formation. Moreover, we identify differentially expressed markers that characterize the two major histological meningioma subtypes both in human and mouse tumours. Collectively, these findings establish the cell of origin for these common brain tumours as well as a susceptible developmental period in which signature genetic mutations culminate in meningioma formation.

Microsurgical and endoscopic anatomy of Liliequist's membrane: a complex and variable structure of the basal cisterns.

OBJECTIVE: Descriptions of Liliequist's membrane, as reported in the literature, vary considerably. In our cadaveric study of Liliequist's membrane, we attempted to clarify and define its anatomic features and boundaries, as well as its relationship with surrounding neurovascular structures. We describe the embryology of this membrane as a remnant of the primary tentorium. The clinical significance of our findings is discussed with respect to third ventriculostomy and surgical approaches to basilar tip aneurysms, suprasellar arachnoid cysts, and perimesencephalic hemorrhage. METHODS: Thirteen formalin-fixed adult cadaveric heads were injected with colored silicone. After endoscopic exploration of Liliequist's membrane, a bilateral frontal craniotomy was performed, and the frontal lobes were removed to fully expose Liliequist's membrane. RESULTS: Liliequist's membrane is a complex and highly variable structure that is composed of either a single membrane or two leaves. The membrane was absent in two specimens without any clear demarcation between the interpeduncular, prepontine, and chiasmatic cisterns. CONCLUSION: Understanding the variable anatomy of Liliequist's membrane is important, particularly to improve current and forthcoming microsurgical and endoscopic neurosurgical procedures. It is important as a surgical landmark in various neurosurgical operations and in the physiopathology of several pathological processes (suprasellar arachnoid cysts and perimesencephalic hemorrhage).

Development of arachnoid villi and granulations in man.

The superior sagittal sinus and confluens sinuum of 27 fetuses and newborns ranging from postmenstrual intervals of 26-54 weeks were studied by scanning electron microscopy and histology. 26-week specimens showed oval depressions in the final portions of tributary veins to the sinus. Histologically there were arachnoid tissue clusters within the dural wall. The walls of the depressions were more irregular by the 30th week. Arachnoid villi were apparent by the 35th week and granulations were observed after the 39th weeks. The granulations increased in complexity as development proceeded.

A morphological study of the development of the leptomeninx of the fetal rabbit cerebrum.

The development of the leptomeninx of the rabbit cerebrum is similar to that of the rabbit spinal cord. At E12 and E14 the leptomeningeal cells resemble immature fibroblasts. At E16 glycogen granules appear in the leptomeningeal cell cytoplasm and are present in pial as well as arachnoid cells. The amount of glycogen decreases from E22 until by E28 it is rarely found in leptomeningeal cells. Leptomeningeal macrophages are present from E12 but granular pial cells were not observed prior to E16. Initially collagen in the pial layer consists of scattered fine fibrils but by E20 collagen is present in larger amounts and the fibrils are of larger diameter and banded.

Human spinal arachnoid septa, trabeculae, and "rogue strands".

This study was undertaken because of confusion arising from a diversity of names, descriptions, and drawings of the human spinal subarachnoid septa and trabeculae in the standard texts and dictionaries. Sixty-two complete human cords were examined under the dissecting scope. The finely "woven" adult arachnoid membrane was two-layered, and there were essentially no connecting septa or trabeculae between the cord and the arachnoid membrane anteriorly. Posteriorly, in the upper cervical region there is a scanty series of connecting fibers and fenestrated sheets 1 or 2 mm on either side of the midline; these become progressively more extensive in the lower cervical region, remain extensive to the lumbar enlargement, beyond which they progressively dwindle to end abruptly at the filum terminale origin. Throughout the cauda equina, strands are haphazardly arranged connecting the roots and supporting blood vessels. These occasionally become tangentially adherent to the arachnoid membrane. Throughout the length there are many unexplained, redundant, nonbranching, beaded, thicker "rogue strands". All of the above are of a different character from the right-angle fiber arrangement of the denticulate ligament, the two leaves of which are often separated form segmental longitudinal tunnels. The nerve rootlets (fila radicularia) for each dermatome are joined by strands and webs to each other. There was no evidence of change in number or type of connection with age.

An ultrastructural study of development of the leptomeninx of the rabbit spinal cord.

Development of the rabbit spinal cord leptomeninges was examined in embryos and fetuses aged 12 to 30 d post-conception. In the early stages of development all mesenchymal cells surrounding the neural tube were structurally similar, resembling immature fibroblasts. At 16 d post-conception cells adjacent to the glia limitans showed little structural change, apart from an increase in the amount of rough endoplasmic reticulum, but cells in the presumptive arachnoid became packed with glycogen. By E22 glycogen was present in pial cells but never in the amounts found in the arachnoid. As development proceeded the amount of glycogen in the leptomeninges declined. Pial collagen increased both in amount and in fibre diameter with age.

Human telencephalic angiogenesis.

We provide new observations regarding the histogenesis and regional development of the human telencephalic microvasculature during the last half of gestation. Endothelium-lined trunks extending from pia to the subventricular plexus, evident early in gestation, persist during the last half of gestation. The courses of these trunks are modified and become complex as the bulk of the telencephalon, striatum, and thalamus increases and as gyri grow. New cerebral tissue is supplied by increasing numbers of shorter penetrating vessels. All extrastriatal vessels have many lateral right- and acute-angle branches that join nearby trunks and shorter vessels. Striatal vessel branches predominantly have acute angles. Most extrastriatal channels remain devoid of apparent muscularis until the final weeks of gestation. In contrast, striatal arteries begin to muscularize at about 24 weeks of gestation. Muscularization appears to occur in a centripetal direction and is apparent in the caudate at approximately 30 weeks' gestation. We did not identify transventricular, paraventricular, or recurrent arteries ending in deep white matter.

The vitreus, an intraocular compartment of the leptomeninx. Electron microscopic observations on rat eyes.

In the 16-day rat embryo and in 2 and 15 days old postnatal rats the macrophage- and fibroblast-like cells of the vitreus are not different from those of the developing leptomeninx. There is also no difference in the ultrastructure of the developing blood vessels. Both vitreus and leptomeninx are separated from the neuroectodermal tissues by a basal lamina. Regarding the embryonic development, the entire intraocular cavity except the lens, is a special cleared-out portion of the former mesenchymal tissues surrounding the central nervous system including the eye cup (meninx primitiva). It may be interpreted as analogous to a leptomeningeal cisterna. The largest part of this intraocular cisterna is the vitreus. The pathogenesis of diseases occurring simultaneously in the leptomeninx, the uvea, and the vitreus, possibly may have some relation to the common embryologic origin of the affected tissues.

Development of the meninges of the human embryonic optic nerve.

From 8 to 14 weeks post-conception the human embryonic optic nerve is surrounded by loosely packed layers of connective tissue. From 8 weeks onwards the innermost layers of this sheath consist of fibroblast-like cells whereas the cells of the middle and outer layers, although similar in appearance, contain increasing amounts of glycogen, until by 14 weeks very large amounts of glycogen are present in these cells. A collagen-rich dural layer first appears at 15 weeks post-conception. This layer contains few cells. The outer-most cells have the appearance of fibroblasts and are joined to each other by long sheet-like processes. Cell in the middle of the dura are glycogen-containing cells, apparently actively engaged in collagen production. These cells are similar to those found in the adjacent arachnoid. By 18 weeks of age the meninges are well-differentiated. The endothelial cells of all capillaries found in the meninges from 8 weeks post-conception, including dural capillaries, are sealed by zonulae occludentes. At 15 and 18 weeks a few fenestrated capillaries were observed at the junction of the dura and the surrounding loose connective tissue. Peripheral nerves are closely related to the meninges from 8 weeks post-conception and peripheral nerve bundles are present in the dura from 15 weeks. At 18 weeks the first signs of myelination were observed in these bundles.