Introduction
Meninges in the developing human and rat brains
Weeks post-conception | Feature | Species | References |
---|---|---|---|
6th | Appearance of a primary meninx around most parts of the brain | Human | O’Rahilly and Müller [70] |
Amoeboid microglial cells penetrate the brain by crossing the pial basement membrane | Human | Verney et al. [100] | |
7th | The skeletogenous layer becomes visible | Human | O’Rahilly and Müller [70] |
Differentiation of a leptomeningeal meshwork that is presumed to contain liquid and represent the future SAS | Human | O’Rahilly and Müller [70] | |
8th | The dural limiting layer is almost complete in hindbrain and midbrain but only present in the area adjacent to the lateral fossa in the forebrain | Human | O’Rahilly and Müller [70] |
The fenestrated sinusoids of the pia–arachnoid become non-fenestrated (E14) | Rat (E14) | Balslev et al. [10] | |
Most of the cisternae of the adult are already present | Human | O’Rahilly and Müller [70] | |
7th–10th | Initial communication between the ventricular and subarachnoid compartments | Human and rat (E17) | |
11th | Completion of the subpial end feet layer (E16) and claudin-11 positive arachnoid blood–CSF barrier (E18) and thereby appearance of a clearly defined SAS | Rat (E16 and E18) | Balslev et al. [10] |
12th–13th | Second wave of microglial cells penetrate the brain via the BBB and inner CSF–brain barrier | Human | Verney et al. [100] |
12 (13th–15th) | Radial glial cells begin to transform into astrocytes | Rhesus monkey (E64) and newborn ferret | |
25th–28th | Transition from subpial end feet layer to glia limitans | Human | Kadhim et al. [50] |
Human brain and meninges
Vascularisation
Development of barriers in the brain
Meninges and claudin-11 in the developing rat brain
Meninges associated with the adult human brain
Dura mater
Leptomeninges
General features of leptomeningeal cells
Distribution of leptomeningeal cells in relation to the CNS
Arachnoid mater
Pia mater
Perivascular compartments and perivascular spaces in the brain
Arteries and veins in the cerebral cortex
Periarterial basement membranes as routes for bulk flow of fluid and solutes into and out of the brain
Leptomeningeal cells surrounding arteries and veins in the cerebral white matter and basal ganglia
Dilatation of perivascular spaces in cerebral white matter and basal ganglia
Leptomeninges as barriers and facilitators in the CNS
Barriers
Arachnoid mater
Leptomeningeal cells separate collagen fibres from the CSF in the subarachnoid space
Choroid plexus
Arachnoid granulations
Facilitators
Arteries and leptomeningeal cells as facilitators for the entry of CSF into the CNS
Tumour cell invasion of subarachnoid spaces and adherence to leptomeninges
Leptomeninges as barriers and facilitators of bacterial meningitis
Meningococcal bacteraemia
Attachment and penetration of vascular endothelium
Molecule | Receptor function and meningococcal ligand recognised |
---|---|
Laminin receptor 1 (LamR; also known as RPSA)–galectin 3 (GAL3) complex) | |
Heparan sulphate proteoglycans (HSPG) | |
Integrins (α1, α2, α3, α4, α5, α6, β1, β4) | Expressed to varying degrees in meningioma/meningeal cells. Bind Opa proteins (which also recognise CEACAM (carcinoembryonic antigen-related cell adhesion molecule) family receptor proteins) and Opc protein [42]. β1-integrin binds NadA (Neisserial adhesin A (autotransporter TAA adhesin–invasin) [66] |
MARCO (Class A Mo scavenger receptor (SR-A) and macrophage receptor with a collagenous structure) | Expressed on (rodent) meningeal cells. Binds to various meningococcal proteins (NMB0278, DsbA; NMB0346, NMB0667, NMB1513, hypothetical; NMB1220, Stomatin/Mec-2 family protein; NMB1567, Macrophage infectivity potentiator) [74] |
CD46 (membrane co-factor protein) | Expressed on all cell types except erythrocytes. Putative receptor for Tfp [51] |
TLR2 | Toll-like receptor 2: pathogen recognition receptor (PRR) for Gram-positive lipoteichoic acid and other lipoproteins and meningococcal PorB [96] |
TLR4 | Toll-like receptor 4: PRR for LOS endotoxin |
Epidermal growth factor receptor (EGFR) | Transmembrane protein with intrinsic tyrosine kinase. Microbial ligand-binding to EGFR potentially activates cell signalling, phosphorylates protein kinases, and rearranges cytoskeletal proteins, thus facilitating pathogen uptake |
HLA-DR | Do phagocytic arachnoid cells act as antigen-presenting cells? |
Interleukin-1R | Binds Interleukin 1 cytokine |
N-CAM | Surface glycoprotein CD56; mimicked by serogroup B CPS |
Fcγ receptors | Potential phagocytosis-related functions; increased by GM-CSF production |
Bone morphogenetic protein (BMP) 4 and 7 receptors | Expressed on leptomeninges—BMPs influence vascular development in this tissue |
CD44 | Multi-structural glycoprotein with functions in cell proliferation, differentiation, migration, angiogenesis, signalling pathways for cell survival, presentation of innate molecules and proteases to receptors |
Desmosomal desmoplakin | Protein component of desmosomes, which are meningeal cell intercellular junctions. Desmosomes function in cell–cell adhesion and for the attachment of intermediate filaments (IF) |
G protein-coupled melatonin receptor Mel1a | Receptor for melatonin that may play role in early neural development |
YKL-40 | Heparin- and chitin-binding glycoprotein, participates in inflammatory states |
β-Type platelet-derived growth factor (PDGF) receptor | PDGF stimulates tumourigenesis in arachnoid cells |
CXCR4 and CXCR7 chemokine receptors | Involved in tumour cell proliferation and survival |
Endothelin receptors | Role in tumour growth |
Epithelial membrane antigen | Marker of meningioma; also known as mucin glycoprotein CD227, MUC1, episialin. Normally acts as a barrier to apical cell surfaces |
Fibroblast growth factor receptor-1 (FGFR-1) | Associated with meningioma cell growth and tumourigenesis |
Mesothelin | Function unknown, possibly a tumour marker |
Prolactin receptor (PRLR) | Detected in meningiomas; proliferative effects |
Sex hormone receptors (progesterone, oestrogen, androgen, aromatase) | May play a role in the tumorigenesis of meningiomas |
Somatostatin receptor (hsst) 2a | Binds somatostatin hormone; diagnostic marker for meningioma |
TGF-β receptors | Receptor loss related to malignancy |
Histones | Intracellular proteins that can associate with App (Adhesion and penetration autotransporter protein) and MspA/Aus1 (meningococcal serine protease A/autotransporter serine protease 1) [53] |