Proteomic interrogation of the meninges reveals the molecular identities of structural components and regional distinctions along the CNS axis.

The meninges surround the brain and spinal cord, affording physical protection while also serving as a niche of neuroimmune activity. Though possessing stromal qualities, its complex cellular and extracellular makeup has yet to be elaborated, and it remains unclear whether the meninges vary along the neuroaxis. Hence, studies were carried-out to elucidate the protein composition and structural organization of brain and spinal cord meninges in normal, adult Biozzi ABH mice. First, shotgun, bottom-up proteomics was carried-out. Prominent proteins at both brain and spinal levels included Type II collagen and Type II keratins, representing extracellular matrix (ECM) and cytoskeletal categories, respectively. While the vast majority of total proteins detected was shared between both meningeal locales, more were uniquely detected in brain than in spine. This pattern was also seen when total proteins were subdivided by cellular compartment, except in the case of the ECM category where brain and spinal meninges each had near equal number of unique proteins, and Type V and type III collagen registered exclusively in the spine. Quantitative analysis revealed differential expression of several collagens and cytoskeletal proteins between brain and spinal meninges. High-resolution immunofluorescence and immunogold-scanning electronmicroscopy on sections from whole brain and spinal cord - still encased within bone -identified major proteins detected by proteomics, and highlighted their association with cellular and extracellular elements of variously shaped arachnoid trabeculae. Western blotting aligned with the proteomic and immunohistological analyses, reinforcing differential appearance of proteins in brain vs spinal meninges. Results could reflect regional distinctions in meninges that govern protective and/or neuroimmune functions.

Subarachnoid space trabeculae architecture.

INTRODUCTION: The motion of the brain relative to the skull is influenced by the architecture of the subarachnoid space (SAS), and in particular, by the arachnoid trabeculae. In previous studies of these structures, specific shapes were identified. However, the work presented here shows much finer detail of the SAS geometries using SEM and TEM. MATERIALS AND METHODS: These images were acquired by maintaining the SAS structure of a rat using glutaraldehyde formaldehyde to strengthen the tissues via crosslinking with the biological proteins. RESULTS: The results showed the detailed shape of five dominant arachnoid trabeculae structures: single strands, branched strands, tree like shapes, sheets, and trabecular networks. Each of these architectures would provide a different response when exposed to a tensile load and would provide different levels of resistance to the flow of the cerebrospinal fluid (CSF) within the SAS. CONCLUSION: This very detailed level of geometric information will therefore allow more accurate finite element models of the SAS to be developed.

Brain Injury and Impact Characteristics.

Almost all studies of traumatic brain injuries have only focused on the maximum acceleration associated with the impact. However, it has been noted that other impact characteristics should also be considered. This study has examined the effect on brain deformation [maximum principal strain (MPS)] associated with changing three characteristics of an isosceles trapezoid acceleration profile: initial slope (jerk), maximum acceleration, and impact energy (maximum velocity squared). This involved using a preexisting finite element model of the brain and applying the trapezoidal acceleration impact to the center of the forehead. The results showed the largest values of MPS were found along a line between the coup and contrecoup positions, and that a strong direct relationship existed between maximum acceleration and brain deformation as measured using MPS. In addition, a strong direct relationship was found to exist between impact energy and brain deformation as measured using MPS. However, it was found that there was almost no observable change in MPS with respect to different jerk values, and in fact there was a slight decrease in MPS as jerk values increased. This comported with a shock spectrum analysis of a simple one dimensional multiple degree of freedom system exposed to similar trapezoidal impulses.

Histology and Morphology of the Brain Subarachnoid Trabeculae.

The interface between the brain and the skull consists of three fibrous tissue layers, dura mater, arachnoid, and pia mater, known as the meninges, and strands of collagen tissues connecting the arachnoid to the pia mater, known as trabeculae. The space between the arachnoid and the pia mater is filled with cerebrospinal fluid which stabilizes the shape and position of the brain during head movements or impacts. The histology and architecture of the subarachnoid space trabeculae in the brain are not well established in the literature. The only recognized fact about the trabeculae is that they are made of collagen fibers surrounded by fibroblast cells and they have pillar- and veil-like structures. In this work the histology and the architecture of the brain trabeculae were studied, via a series of in vivo and in vitro experiments using cadaveric and animal tissue. In the cadaveric study fluorescence and bright field microscopy were employed while scanning and transmission electron microscopy were used for the animal studies. The results of this study reveal that the trabeculae are collagen based type I, and their architecture is in the form of tree-shaped rods, pillars, and plates and, in some regions, they have a complex network morphology.